Cardiovascular disease rarely is caused by a single frailty. Rather, it is a multifaceted failure that includes physical, psychological, and genetic weaknesses. Since cardiovascular disease remains the number one killer in Western societies, there is more published scientific information about prevention and treatment than exists for other diseases. This Cardiovascular Disease protocol is the longest chapter in this book, but we urge those concerned with the disease to study it carefully. Overlooking just one risk factor, such as elevated levels of C-reactive protein, fibrinogen or homocysteine, could lead to the development or worsening of heart and/or vascular disease.

At least 68 million people in this country suffer from some form of heart disease, with an estimated 1.1 million Americans, annually, experiencing an acute myocardial infarction (heart attack). According to statistics released from the National Heart, Lung, and Blood Institute's Atherosclerotic Risk in Communities (ARIC) Study, of those numbers over 40% die. Dr. Kenneth Chien, a cardiologist and molecular biologist, states that improved post-infarction care has resulted in greater numbers surviving a heart attack, but the long-term prognosis may still be bleak. Dr. Chien warns that as primary mortality decreases, the incidence of morbidity, i.e., an increase in the incidence of heart failure is increasing among heart attack survivors.

Reports appearing in the American Journal of Critical Care further unsettled the scientific community when they declared that 50% of the patients with coronary artery disease do not have any of the traditional risk factors. (Futterman et al.,1998) In fact, 50% of all individuals 50 years or younger, who die from heart disease, succumb without any established risk factors. Does this mean that traditional risk factors are no longer valid? The intent of this material is to answer that question, by providing a comprehensive view of contemporary and novel risk factors that contribute to cardiovascular disease and a complete dialogue regarding treatment options available to patients.

BALDNESS

Male pattern baldness is a subject of interest, in regard to the incidence of coronary heart disease (CHD). The Department of Medicine at Harvard Medical School and Brigham and Women's Hospital conducted an 11-year study involving 22,071 male physicians, to determine the relationship between baldness and CHD. The study evaluated the following patterns of hair growth: (1) no hair loss, (2) frontal baldness only, and (3) frontal baldness with mild, moderate or severe vertex balding (vertex refers to the top of the head). The Harvard study concluded that the risk of CHD increased progressively throughout the different groups, with vertex balding showing the greatest association. Vertex baldness appears a valid marker for an increased risk of coronary heart disease, particularly when clustered with other factors, such as hypertension or hypercholesterolemia (high cholesterol).

EARLOBE CREASES

Around 1973, the association between diagonal earlobe creases and the threat of an eventual heart attack was made. Chronic circulatory problems allow the vascular bed in the earlobe to collapse and the telltale earlobe crease to appear. More than 30 studies have been recorded in the medical literature, with the largest study, to date, involving 1,000 randomly selected patients. Diagonal earlobe creases, appearing at a 45-degree downward angle toward the shoulder, appear a better predictor of sudden death from a heart attack than age, smoking, obesity, elevated cholesterol levels, or a sedentary lifestyle.

It appears that individuals with an earlobe crease have a 55% greater risk of dying from heart disease than those without the marking, with the risk becoming even more prognostic if diagonal creases appear on both ears. The predictive value, of the diagonal earlobe crease, does not apply to Orientals, Native Americans, or children with Beckwith's syndrome, a heredity disorder associated with neonatal hypoglycemia and hyperinsulinism.

While earlobe creases do not prove heart disease, the Mayo Clinic announced that out of 121 patients, the earlobe crease plus symptoms of heart attack (i.e., chest pain) meant a heart attack about 90% of the time. Similar symptoms but without the earlobe crease terminated in a non-coronary diagnosis 90% of the time.

SMOKING

Kentucky and Tennessee have the highest rates of heart disease deaths, but also the highest rates of cigarette smoking. Prolonged exposure to cigarette smoke, either direct or second hand, increases the risk of dying from a heart attack or complications arising from atherosclerosis, by three to fivefold. Much of the ill-omened health effects related to smoking occur due to an increase in free radical activity. Unfortunately, as the population of free radicals increases, vitamin C, a powerful antioxidant, decreases in the smoker.

Many explanations have been documented, explaining the hardship that cigarette smoking imposes upon the cardiovascular system. Increased heart rate (one cigarette can increase the heart rate 20 to 25 beats per minute), disrupted circulation to the legs and feet (it takes 6 hours for the circulation to return to normal after just one cigarette), lowered skin temperature, increased need for oxygen, insulin resistance, hypertension, and increased levels of adrenaline are some of the hazards associated with smoking. Note: Smoking doubles blood levels of adrenaline; the results are vaso-constriction and platelet aggregation, increasing the risk for both heart attacks and strokes.

Earl Mindell, R.Ph., Ph.D., warns that smokers have higher levels of fibrinogen. Fibrinogen is necessary for proper clotting of blood, but abnormally high levels of fibrinogen can cause blood clots to form spontaneously. It is judged that smoking accounts for half of the vascular risks attributable to fibrinogen.

Cigarettes contain toxic substances (there are 4,000 poisons contained in tobacco) some of which inactivate vitamin B6, a nutrient extremely important in homocysteine control. Homocysteine management is, typically, difficult in smokers. (Consult the Newer Risk Factors section of this protocol for a complete discussion regarding homocysteine and to the Therapeutic Section for a supplemental regime to maintain healthy homocysteine levels.)

The Lancet added to the concerns surrounding smokers when they reported that men with the lowest serum albumin levels have the highest rate of death from various causes, including heart disease. (Schatz et al., 2001) Smoking lowers this predictive protein.

Data published in the Journal of the American Medical Association (JAMA), indicates that the critical phase of cardiovascular disease is, significantly, accelerated in the smoker. (Grundy, 1986) The critical phase is marked by 60% coverage of arterial surfaces with atheromatous materials. Though the ages were hypothetically assigned, a smoker with normal blood pressure and cholesterol levels reaches the critical phase 10 years earlier than the non-smoker and 20 years earlier if the smoker is, also, hypertensive.

It is estimated that each cigarette steals 8 minutes of life from the smoker. This means that an individual smoking one pack a day loses a month of life each year. Two packs clip 12 to 16 years off of life expectancy for lifetime smokers. It is important, however, for the smoker to realize that the body has immense capacity for restoration. Within 24 hours of being tobacco free, the chance of heart attack decreases. Within 48 hours nerve endings start to regroup and breathing becomes noticeably improved. Within two to three months, circulation improves and walking becomes easier. Lung capacity increases up to 30%, and energy levels rebound. After one year, the risk of a heart attack is 50% less than the individual still smoking; within two years, the risk of heart attack drops to ranges closely rivaling an individual who has never smoked. Another bonus occurs as inflammation (a newer of the risks associated with heart disease) is reduced and subsequently C-reactive protein (CRP), an inflammatory marker also decreases. (Turn to Newer Risk Factors to read more concerning CRP and the role of inflammation in the onset of heart disease.)

Though the body is resilient, it is extremely important that the smoker not wait too long to embark upon recovery. For information pertaining to nutrients that offer protection to the smoker, turn to bromelain, coenzyme Q10, curcumin, proanthocyanidins, vitamin C, and vitamin E in the Therapeutic Section of this protocol.

HYPERTENSION

Hypertension (high blood pressure), observed more in men and blacks, is a disorder characterized by blood pressure persistently exceeding 140/90 mmHg. Current research indicates that optimal blood pressure is <120/80 mmHg and normal is 120-129 over 80-85. It is important to note that damage to the vasculature can occur when the blood pressure is moderately but chronically elevated. Some individuals may not realize they are hypertensive since symptoms as epistaxis (nosebleed), tinnitus, dizziness, headache, blurred vision, and arrhythmias are not always present.

Dr. Charles DeCarli, of the University of Kansas, found that men who had even mildly elevated blood pressure 25 years earlier now have abnormal brain signals and more vascular disease and strokes than men who had normal blood pressure in midlife. "Take care of risk factors when you're young or they'll come back to haunt you," warns DeCarli.

The Archives of Internal Medicine reported results of the most comprehensive study to date, evaluating 10,874 Chicago men (ages 18 to 39) from 1967-1973 concerning the long-term effects of high blood pressure. (Katsuyuki et al., 2001) About 62% of those studied had either high-normal blood pressure (systolic pressure 130-139 and diastolic pressure 85-89) or stage 1 hypertension (systolic pressure 140-159 and diastolic pressure 90-99).

Life expectancy was shortened by 2.2 years for men with high normal blood pressure and by 4.1 years for those with stage 1 hypertension. This means an individual with a high-normal blood pressure has a 34% higher risk of dying from coronary heart disease; those with stage 1 hypertension have a 50% higher risk of dying of coronary heart disease. After 25 years, 197 of the men had died of coronary heart disease, 257 of cardiovascular disease, and 759 from other causes, some of which might, also, be attributed to high blood pressure, as kidney disease. Dr. David A Meyerson, a Johns Hopkins cardiologist and spokesman for the American Heart Association, said the study affirms the need for disease prevention through lifestyle modification. The commitment should be begun early in life and continued lifelong.

Findings published in the New England Journal of Medicine (exploring the role of moderately elevated blood pressure as a forerunner of heart disease) concurred with results gathered from the Chicago/ hypertension trial. (Vasan, 2001) The parameters describing moderately elevated blood pressure were identical in both trials, i.e., a systolic pressure of 130 to 139 mmHg and a diastolic blood pressure of 85 to 89 mmHg, or both.

Researchers, tracking the 6859 participants, noted a stepwise increase in cardiovascular events among persons with higher base line blood pressure. The 10-year cumulative incidence of cardiovascular disease in subjects 35 to 64 years of age with high-normal blood pressure was 4% for women and 8% for men. In older subjects (those 65 to 90 years of age), the incidence was 18% (women) and 25% (men). As compared with optimal blood pressure, high-normal blood pressure was associated with a risk factor-adjusted hazard ratio for cardiovascular disease of 2.5% in women and 1.6% in men. Thus, the results of various credible studies demonstrate that high-normal blood pressure should not be taken lightly; a regime to counter even a slight rise in blood pressure (exceeding optimal/normal levels) should be regarded as essential to reducing cardiovascular risk.

For decades it was thought that the diastolic (the lower blood pressure) was the most critical measurement when diagnosing hypertension and assessing blood pressure-induced vascular damage. The journal Hypertension renounced this theory, reporting that systolic pressure is the crucial assessment, not the diastolic as previously considered. (Izzo et al., 2000) (Systolic pressure represents the maximum force exerted by the heart against the blood vessels during the heart's pumping phase.) The difference between the systolic and diastolic blood pressure is referred to as pulse pressure; if the number chronically exceeds 60, advanced atherosclerosis is, usually, evidenced.

While most cases of high blood pressure are classed as essential or primary hypertension (meaning no known cause can be found for the elevation), it is a misnomer to imply that unfounded hypertension is innocent. Any sustained elevation of blood pressure can affect the intima (innermost structure) of small vessels, brain, retina, kidneys, and heart.

Secondary hypertension is, frequently, linked to primary diseases, such as renal, pulmonary, endocrine, and vascular disease. Malignant hypertension, the most lethal form, is characterized by severely elevated blood pressure that commonly damages small vessels, brain, retina, heart, and kidneys. Many patients with this condition exhibit signs of hypokalemia (inadequate levels of potassium in the bloodstream), alkalosis (blood pH >7.44), and excessive aldosterone secretion (a hormone that conserves water and sodium and increases potassium excretion).

Hypertension increases the risk of cardiovascular disease by affecting the performance of arteries. Normally, arteries expand and contract effortlessly with each heartbeat. With sustained hypertension, arterial walls become thickened, inelastic, and resistant to blood flow. This process injures arterial linings and accelerates plaque formation. Non-functional, blocked vessels are unable to expand to accommodate the flow of blood and the left ventricle is forced to pick up the slack. The endless exertion proves too much and the ventricle may become distended and hypertrophied. In exhaustion, the pump eventually fails. The health of the left ventricle is an extremely important assessment when evaluating the worthiness of the heart.

Arterial damage is invitational to spasms occurring in the walls of the arteries. The spasm further impedes the flow of blood, adding additional challenge to the ailing heart as it works to move the blood against the backpressure. Lack of egress and the heart's aggressive action can cause a weakened area in the arterial wall to balloon, forming an aneurysm. Rupture of the artery can result in massive internal bleeding and death. An aneurysm or stroke, angina pectoris, and myocardial infarction are even more likely to occur if hypercholesterolemia and hypertension coexist.

Serum creatinine levels in hypertensive patients are an extremely important marker, and, unfortunately, one frequently ignored. Creatinine is proving highly reliable in predicting cardiac outcome in individuals with high blood pressure. Researchers analyzed data from a massive study involving 14 U.S. medical schools and 10,940 participants. It was determined that 50% of hypertensive individuals with creatinine levels of 2.5 mg/dL (or greater) will die within 8 years, according to Dr. Neil B. Shulman, principal investigator (Emory University). Cardiac deaths begin to spiral when creatinine levels reach 1.2 mg dL, with fatalities mounting as creatinine increases. Though high levels of creatinine frequently reflect kidney impairment, most individuals with high creatinine die of heart attacks and stroke, not renal disease.

Patients are searching for alternatives to hypertension medications in light of information gathered from an 8-year study involving 117,534 people. Half of the individuals were given anti-hypertensive drugs and the other half a placebo. The number of deaths at the end of the 8-year study was about the same in each group; the side effects of the drugs, however, eroded the equality of the results. Note: Additional information regarding the ineffectiveness of drug therapy among many hypertensive patients may, also, be read in the British Medical Journal, Nuesch et al, 2001.

Syndrome X, one of the newer cardiac risk factors, may best explain why some individuals are not protected from heart disease when hypertension is treated independently. Excesses of insulin, a hallmark of Syndrome X, make dominant the sympathetic nervous system and the release of catecholamines, i.e., dopamine, epinephrine, and norepinephrine, which contribute to hypertension by diminishing blood vessel diameter. Hyperinsulinemia, also, encourages retention of salt and water, a process that increases blood volume and blood pressure. About 50% of hypertensive patients are insulin resistant and should be treated for this condition primarily, rather than focusing on a symptom of the syndrome, i.e., high blood pressure. Gerald Reaven, Professor Emeritus (Active) of Medicine at Stanford University, states that it is vital that every healthy-heart program address the hypertension/ Syndrome X association or little success in shielding hypertensive patients from heart attack can be expected.

If anti-hypertensive drug therapy is used, Cozaar or Hyzaar (angiotensin II antagonists), appear safer and more effective than short-acting calcium channel blockers. It should be noted that beta-blockers and diuretics (anti-hypertensive treatments) have been associated with an increased risk of developing diabetes by impairing insulin sensitivity. (Lithell, 1996) New generation calcium channel blockers are, generally, neutral in regard to advancing diabetes, but exceptions occur. Striking benefits have been obtained with alpha 1-blockers in hypertensive populations at high risk for developing diabetes mellitus. Since credible options are available, the patient is strongly advised to opt for anti-hypertensive drugs that actually improve insulin sensitivity, avoiding drugs with the potential of causing diabetes.

RESULTS OF THE HOPE PROJECT

On March 11, 2000, a satellite symposium of the American College of Cardiology Scientific Session (Anaheim, CA) was held during which several speakers discussed the results of the Heart Outcomes Prevention Evaluation (HOPE) study, a 6-year trial assessing the value of ramipril, an angiotensin-converting enzyme (ACE) inhibitor in the prevention and management of cardiovascular disease. (Ramipril, a generic of the drug Altace, is principally used in the treatment of high blood pressure but its cardiovascular benefits appear far-reaching.) During the study, researchers also sought to determine whether vitamin E was more effective than a placebo in preventing major cardiovascular outcomes.

A brief explanation of the renin-angiotensin system follows:

The juxtaglomerular cells in the kidneys stimulate renin secretion when either blood volume or serum sodium decreases. Renin, an enzyme, participates in the conversion of angiotensinogen to angiotensin I, which is rapidly hydrolyzed to form the active compound, angiotensin II. The vasoconstrictive action of angiotensin II decreases the glomerular filtration rate; the concomitant action of aldosterone, a mineralocorticoid hormone produced by the adrenal cortex, promotes sodium retention, causing blood volume and sodium reabsorption to increase. Agents that inhibit the angiotensin-converting enzyme decrease sodium and water retention, reduce blood pressure, improve cardiac output, and, typically, decease heart size.

Some 9500 people from 270 hospitals in 19 countries participated in the HOPE study. Included in the trial were those with evidence of vascular disease, i.e., coronary artery disease, stroke or peripheral vascular disease, and high-risk patients with diabetes. Subjects were randomized to one of four treatments: ramipril alone, vitamin E alone, ramipril and vitamin E, or neither.

Dr. Salim Yusuf, Ph.D., (Professor of Medicine and Director of the Division of Cardiology, McMaster University (Ontario, Canada) reported the HOPE study showed that ramipril reduced the risk of new heart attacks, strokes, and mortality by 20% to 25%. (Lancet, 1993) Incidences of coronary revascularization, heart failure, and complications related to diabetes were significantly reduced as well. Dr. Yusuf reported on another phase of the HOPE study (the effectiveness of vitamin E as a cardio-protector) announcing that no beneficial effects were evidenced with vitamin E supplementation.

As frequently occurs when trial results are overwhelmingly in favor of one treatment over others, the study was halted. The ramipril treated group received such obvious benefit, it was deemed unethical to withhold the drug from the control group. (The SECURE study, a subset of the HOPE project, also found that ramipril was effective at impeding the progression of atherosclerosis, but found no positive effects attributable to vitamin E therapy.) So effective was ramipril, Dr. Victor Dzau, M.D., Professor of Theory and Practice of Medicine at Harvard Medical School, suggests that it might be helpful (in certain cases) to use ACE inhibitors to reduce risks of potentially costly problems even in the absence of hypertension.

Of tremendous interest was the finding that patients with diabetes experienced a reduction in diabetic neuropathy and the progression of the diabetic process while using ramipril. Over the four and one-half years of the HOPE study, the number of patients who developed new diabetes in the ramipril group was one-third that of the placebo group. If the ramipril/diabetes advantage can be confirmed, it would indicate that the renin-angiotensin system is, also, involved in the pathogenesis of diabetes. Bolstering the hypothesis, Captopril, another ACE inhibitor, also results in an improvement in insulin sensitivity.

According to Dr. Bertram Pitt, Professor of Internal Medicine at the University of Michigan (Ann Arbor) the HOPE study confirms that activation of the renin angiotensin system is an important risk factor for a heart attack. When angiotensin II is elevated in the vascular wall, it affects the transport of cholesterol into the wall and its oxidation, as well as increasing cytokine numbers. This begins a cycle, i.e., high levels of low-density lipoproteins (LDLs) leads to an increase in angiotensin II, which in turn increases oxidation of LDL cholesterol. The power of ACE inhibitors (such as ramipril) to prevent cardiovascular events is partially explained by their ability to interrupt this cycle.

An interesting finding was that the benefit derived from ramipril was independent of blood pressure modulation. A reduction of only 3 systolic points and 1.8 diastolic points from a mean baseline of 138/76 mmHg was observed. Nonetheless, a clear reduction in unwanted outcomes, i.e., cardiovascular death, myocardial infarction, and stroke, occurred in all blood pressure categories. Dr. Yusuf speculates that two million people (per year) could be spared a major cardiovascular event if ramipril were widely used.

Dr. Dzau explains that within unstable atherosclerotic plaque, a great deal of inflammation has been observed, and inflammatory cells produce angiotensin II. This situation is complicated by the fact that angiotensin also leads to inflammation. The result is the creation of a sequence that leads to constantly increasing levels of angiotensin production and inflammation, a cycle invitational to the progression of atherosclerosis and ischemic events.

Researchers were impressed with the absence of side effects during the course of the trial. If a patient has hypercholemia (an excess of chloride in the blood) or renal dysfunction, the physician should, however, be very careful about administering any ACE inhibitor. If ramipril is to be used, 10 mg per day appears the optimal dosage. (The SECURE study found lesser dosages ineffective.) Hypotensive patients should start at a lower dose, such as 2.5 mg and gradually increase. It is uncertain whether all ACE inhibitors are equal to ramipril in delivering cardioprotection; the ACE inhibitor quinapril failed in reducing ischemic events, but researchers question whether the dosage was more in error than the drug.

Comments regarding the unfavorable review of vitamin E: Dr. Richard Passwater, a long-time vitamin E devotee, explains that the length of time vitamin E is used determines its cardiovascular defense. The trend is especially apparent beyond nine years. Passwater showed that taking 400 IU of vitamin E daily for 10 years or more, dramatically, reduced the occurrence of heart disease prior to 80 years of age. (Turn to vitamin E, in the Therapeutic Section of this protocol, to read about Dr. Passwater's study, as well as current documentation supporting supplementation to protect against cardiovascular disease.) Also, the type and blend of vitamin E selected can alter outcome. The Life Extension Foundation has long advocated a complex of alpha-tocopherol (80%) with gamma-tocopherol (20%) for optimal protection when supplementing with vitamin E.

In contrast to the HOPE study, the Lancet reported the benefit of administering 800 IU/day of vitamin E to individuals with pre-existing cardiovascular disease and on haemodialysis. (Boaz et al., 2000) Increased oxidative stress, imposed through dialysis, appears to increase cardiovascular mortality. Supplementing with vitamin E reduced composite cardiovascular disease endpoints and myocardial infarction by about 50% compared to the placebo group. While bewildering to the consumer, varying dosages applied to diverse populations, often, results in unlike endpoints and dissimilar conclusions.

The Therapeutic Section highlights numerous suggestions to treat hypertension, as alpha lipoic acid, angelica, L-arginine, calcium, coenzyme Q10, essential fatty acids, garlic, hawthorn, magnesium, olive leaf extract, 3-n-butyl-phthalide, policosanol, potassium, taurine, and vitamin C. Natural ACE inhibitors are green tea, garlic, hawthorn, olive leaf, taurine, proanthocyanidins (mild ACE inhibition), angelica, and ginkgo biloba.

To read about the influence other conditions has upon hypertension, consult the following sections within this protocol: Smoking, Obesity, Stress, Genetics, Fibrinolytic Activity, Homocysteine, Syndrome X, Chelation Therapy, and Does Sodium Restriction Lower Blood Pressure.

OBESITY

Excessive body weight is a risk factor in so many diseases, that obesity, itself, is now regarded as a disease. In America 104.4 million adults are overweight and 42.5 million are obese. Considering these alarming numbers, it is prudent to wonder when a troublesome weight problem is no longer just an annoyance but a significant risk to heart disease? Measuring body mass index (BMI) has helped physicians and patients answer this question. BMI may be figured as follows:

	Convert weight into kilograms by dividing total weight by 2.2.
	Determine height and convert to inches.
	Convert height in inches to meters. (One meter equals 39.37 inches.) Divide the height in inches by 39.37.
	Square the height in meters by multiplying it by itself.
	Divide the weight in kilograms by the height in meters squared.

During the American Heart Association's 71st Scientific Session in 1998, guidelines for assessing the risks imposed by obesity (as measured by BMI) were reported. This study was based on data from the Framingham Heart Study and the Third National Health and Nutrition Examination Survey. The results follow in figure 2.

The pattern of the fat distribution is another important prognosticator of host vulnerability. For example, android obesity or male pattern obesity is characterized by central abdominal obesity. Android obesity, i.e., apple-shaped bodies, is, historically, associated with an increased risk of hypertension, diabetes, hyperinsulinism, cardiovascular disease, and premature death. Conversely, fat distribution confined primarily to the hips and thighs, i.e., gynoid or pear shaped obesity, is more likely to be regarded as benign and is common in females.

Research has clarified the reasons fatness increases cardiovascular risks. Obesity forces the heart into intensive labor, since the useless pounds must be serviced in the same fashion, as valuable tissues and organs. The risk of diabetes and hypertension increases almost three times in obese individuals. In fact, losing as little as 2 pounds can result in a 1-2 point reduction in blood pressure. Blood cholesterol levels increase by about 2 mg/dL for each kilogram (2.2 pounds) of excess body weight; fasting blood glucose levels increase about 2 mg/dL for every 10% over ideal body weight. (It has been confirmed that a diabetic can reduce their cardiovascular risk by losing as little as 5 to 10 pounds.) Other factors increasing cardiovascular risk as excessive fibrinogen, elevated C-reactive protein, and insulin resistance, often, share a common denominator, i.e., obesity.

A 10-15 pound weight loss can, also, lessen the risk and progression of Syndrome X, a condition of insulin resistance and hyperinsulinemia. As weight drops, tissues become more insulin sensitive, amending a primary identifiable trait in Syndrome X. Though not all obese individuals develop Syndrome X, the more overweight one is, the greater the risk of developing the syndrome and the clusters of disease factors surrounding it. (A discussion of Syndrome X as an antecedent to cardiovascular disease may be found in the section devoted to newer cardiovascular risk factors.)

Overeating in the absence of obesity poses a cardiac risk, as well. Reports from patients indicated that unusually heavy meals were, often, consumed during a 26-hour period preceding the myocardial infarction (heart attack).

It is apparent that individuals need to establish a sensible approach to eating, i.e., a program that can be comfortably maintained long-term, void of either binges or periods of starvation. To lose weight only to regain it poses many health risks. For example, a decrease in HDL cholesterol is, often, reported in women who chronically cycle their weight from highs to lows. (Merz, 2000) Weight cycling is defined as intentionally losing at least 10 pounds three or more times during one's life. Weight cyclers, typically, have a 7% lower HDL cholesterol than non-cyclers. (Olson et al., 2000)

For dietary supplements that may assist in weight loss, read about L-carnitine, chromium, CLA, coenzyme Q10, fiber, hawthorn, and zinc in the Therapeutic Section of this protocol.

DIABETES

The degenerative process that accompanies diabetes, significantly affects the heart. Atherosclerosis tends to develop early, progress rapidly, and be more virulent in the diabetic. Data released from the Framingham Study showed a fourfold increase in heart failure in diabetic men under age 65 and an eightfold increase in young diabetic women.

Diabetics are particularly susceptible to silent myocardial infarctions, i.e., an asymptomatic attack that interrupts blood flow to the coronary arteries. Understanding Normal and Clinical Nutrition reported that more than 80% of people with diabetes die as a consequence of cardiovascular diseases, especially heart attacks. (Whitney et al., 1998) High homocysteine levels, also, play a significant role in diabetes-induced cardiovascular disease. In fact, hyperhomocysteinemia is considered a reliable predictor of mortality among diabetic patients.

Much of the stress of diabetes is due to a constant state of flux, i.e., moving from hyperglycemia to hypoglycemia in a relatively short period of time. Non-diabetics are spared glycemic-induced stress. For example, most healthy individuals maintain post-absorptive blood glucose levels of 90-100 mg/dL. Even after fasting or overeating, blood glucose levels seldom fluctuate lower than 60 or over 160 mg/dL. It has been suggested that evolutionary success requires staunch defense of the range of blood sugar, since exceeding the limits at either end produces dire circumstances. An unstable diabetic lacks the homeostatic mechanisms that provide for intricate glucose balance and, as a result, the heart and circulatory system suffer.

Typically, type 2-diabetes develops because of a lack of insulin sensitivity at the cellular level. As a result, the bloodstream becomes overloaded with non-functional insulin and a glut of glucose. The reason for this is that as glucose is increasingly unable to be used for energy metabolism and accumulates in the blood, the pancreas secretes more insulin in a futile attempt to restore normal glycemic control. After an extended period of excess insulin secretion, the pancreas may lose its ability to produce insulin and the Type II diabetic may then become insulin dependent.

When insulin loses its sensitivity or receptivity, its metabolic disposition changes, becoming more an adversary than an advocate. Cholesterol and other lipids are more likely to be deposited on arterial walls; hypertension, impaired coagulation, and obesity are common problems. Of all the hormones, insulin (in excess) has the greatest influence upon weight gain.

Chronic hyperglycemia causes monocytes and adhesion molecules to bind to vessel walls. Lipids become disorganized, with more of the LDL cholesterol and less of the beneficial HDL appearing in the bloodstream. The volume of urine produced increases and dehydration may result. Life-saving minerals are often excreted with the urine and electrolyte imbalances can occur. As vital minerals are pulled from the system, the heart can be forced into fatal arrhythmias.

During hypoglycemia (a condition of low blood glucose levels that can occur in less stable diabetic patients), the ability of the nervous system to function decreases, but the breakdown of fats increases. In this guise, the fat assumes the role of a glucose surrogate. Necessary as this mechanism is, it is not without disadvantage. Substitute pathways are not always well regulated, and excess fats, not used as an energy source, may accumulate, contributing to the atherogenic process.

Symptoms of hypoglycemia can mimic a heart attack, i.e., dizziness, fatigue, sweating, shakiness, lightheadedness, palpitations, and in some cases, unconsciousness. Normal brain function requires 6 gm of glucose per hour, which can be delivered only if arterial blood contains over 50 mg/dL of glucose. Though hypoglycemia is not a heart attack, the stress imposed upon the heart can be extreme.

To learn more about the impact obesity, stress, gender, sedentary lifestyle, fibrinolytic activity, and syndrome X has upon diabetes, consult the Traditional and Newer Risk Factors section of this protocol. For natural suggestions to benefit the diabetic, read about alpha lipoic acid, L-carnitine, chromium, DHEA, essential fatty acids, fiber, garlic, magnesium, olive leaf extract, selenium, vitamin A, vitamin E, vitamin K, and zinc in the Therapeutic Section (appearing later in this protocol).

HYPERCHOLESTEROLEMIA AND DERANGED LIPID PROFILES

Too much cholesterol is not good, but too little may not be either. The American Heart Association announced in 1999 (at the annual stroke conference) that people with cholesterol levels less than 180 mg/dL doubled their risk of hemorrhagic stroke compared to those with cholesterol levels of 230 mg/dL. Studies indicate that low serum cholesterol levels may, also, increase the risk of death due to cancer, particularly lung cancer. Canadian investigators reporting in Epidemiology reported that after adjusting for age and sex, they found that those in the lowest quarter of total cholesterol concentrations had more than six times the risk of committing suicide, as did those in the highest quarter. (Ellison et al., 2001)

The New England Journal of Medicine reported that though there has been concern for hemorrhagic stroke in hypocholesterolemic patients, a current study did not support this fear. (White et al., 2000) Until the quandary has been resolved, there are reasons to be cautious about severely reducing dietary fat and serum cholesterol. Recall that triglycerides, the largest of the fat molecules in the body, carry the fat-soluble vitamins (including vitamin K, an extremely important nutrient in normal blood coagulation). Also, platelets (cells essential to blood coagulation) are, in part, made from cholesterol, which, if in short supply could influence platelet numbers. Other researchers believe that hypocholesterolemia weakens arterial walls in the brain, making them susceptible to breakage under pressure. (About 20% of all strokes result from cerebral hemorrhages.)

Cholesterol is so important that the body produces from 800 to 1500 mg each day to provide for the following metabolic processes:

	Cholesterol is present in every cell in the body, strengthening cell walls and assisting in the exchange of nutrients and waste materials across the membranes.
	The central nervous system, composed of the brain and spinal cord, contains nearly one-fourth of the body's store of cholesterol. As much as 50% of myelin, surrounding nerves is cholesterol. Cholesterol is essential for the conduction of nerve impulses.
	Bile acids, formed from cholesterol, are vital for proper fat digestion.
	Cholesterol is the precursor of adrenal and reproductive steroid hormones.
	Surface cholesterol makes the skin resistant to chemicals and disease organisms, hindering entry through pores. Cholesterol stored in the skin assists in converting sunlight to vitamin D.

Though high concentrations of total serum cholesterol are related to mortality in individuals younger than 65 years, clinical trials have failed (until recently) to look at large numbers of individuals (>70 years of age) to assess their response to higher cholesterol levels. According to data published in the Lancet, the risk imposed by hypercholesterolemia decreases with age. (Weverling et al., 1997) (Schatz et al., 2001) In fact, low cholesterol may be associated with higher death rates among elderly people, due to mortality from cancer and infection. Cholesterol can assume the role of modulator, controlling cell signaling, reducing inflammation, and assisting in cellular repair. Therefore, administering a hypocholesterolemic drug to a senior subject may, actually, increase their risk of succumbing with other forms of degenerative disease.

Dr. Steven Whiting, Dean of the Institute of Nutritional Science, explains how cholesterol can change from an essential sterol to an atheromatous material. Free radicals and hypertension can damage the inside of an artery, causing a small rupture or tear to occur. The body recognizes the problem and attempts to handle it, with the materials available. Fibrin, a stringy, insoluble protein, is the first material laid down at a wound sight. Fibrin has done what it must, seal or coat the damaged area in the artery. Unfortunately, fibrin can grasp other bloodstream infiltrates in its web-like structure, i.e., collagen proteins and minerals that have precipitated out of solution. A significant bump in the arterial pathway has developed, when along comes cholesterol. Cholesterol appears to add the final coat to the plaque, building up in the artery.

An inverse relationship exists between high-density lipoproteins (good cholesterol) and cardiovascular disease. The HDL2 subfraction is even more correlated with cardiac protection and longevity than total HDL cholesterol.

(Sardesai, 1998) Typically, low triglyceride/LDL levels and high HDL levels, place an individual in a better posture cardiovascularly.
HDL levels are considered desirable in a range of 55-70 mg dL. Total cholesterol, for most individuals, appears best managed between 180-200 mg/dL. The "how low can you go" logic is not wise when setting relevant cholesterol goals, considering the many functions assigned to cholesterol and the unsettled questions surrounding the safety of very low cholesterol levels.

Risk factors for heart disease are often calculated by dividing the total cholesterol by the HDL. Assessment of HDL/total cholesterol ratios is not standardized but, according to Health and Wellness (sixth edition), a value of 4.5 places the individual at an average risk, ratios above 4.5 indicate an increased risk, and ratios below 4.5 mean a decreased likelihood of developing heart disease. (Edlin et al., 1999)

Most laboratories use a reference range of 90-130 mg/dL for LDL cholesterol, but LDL appears optimal at 100 mg/dL or lower. It is purported that a 1% reduction in LDL cholesterol lessens the risk of heart attack by 2%. (LDL cholesterol is not measured directly; levels are calculated using the following formula: LDL = Total Cholesterol - HDL - (Triglycerides/5.)

Cholesterol tests, indicating acceptable levels, may convey a false sense of security. Current research indicates that standard tests miss 50% of people at risk for heart attack, due to the inability to detect abnormally small cholesterol particles. (Excessive insulin production, a hallmark of Syndrome X, is a factor that causes LDL cholesterol to assume a smaller, denser configuration.)

LDL pattern B is the smallest and most susceptible to oxidation of all forms of cholesterol. Both LDL pattern B and lipoprotein(a) increase the risk of heart attack by threefold, and cannot be detected by standard cholesterol tests. Without detection of the smaller cholesterol subsets and appropriate treatment, plaque buildup progresses twice as fast. Trapped LDL or lipoprotein(a), over time, forms plaque with a fibrous cap. Unstable plaque can rupture which causes the blood to clot, increasing the risk of sudden heart attacks or strokes. Laboratories providing total screening, i.e., testing for normal and abnormal sized lipoproteins should be used for evaluations.

Triglyceride levels are, usually, regarded within a normal range at 30-199 mg/dL, but Clin Rev Spring reported that patients with clinical coronary heart disease were less likely to experience new events if triglyceride levels were <101 mg/dL. (Kreisberg et al., 2000) Most researcher/physicians agree that triglyceride levels are best maintained below 100 mg/dL. According to information obtained from The Anti-Aging Zone, the ideal ratio of triglycerides to HDLs is less than 1. A ratio of 1.5 is acceptable, but a ratio of 2 and above should be reason to take action. (Sears, 1999)

Individuals with high triglycerides and low HDL cholesterol are 16 times more likely to have a heart attack than a person with normal levels. Triglyceride levels rarely rise unless one is suffering from insulin resistance or hyperinsulinemia, conditions often modifiable by controlling carbohydrate in the diet. According to data reported in Atherosclerosis, elevated triglyceride levels usually modulate when less food is consumed, particularly foods causing a rise in blood sugar levels, i.e., bakery products, pastas, and foods with added sugar. (Stavenow et al., 1999)

Other areas relating to hyperlipidemia are: heredity, sedentary, lifestyle, gum disease, hypothyroidism, hemochromatosis, fibrinogen, Lp(a), homocysteine, Syndrome X, and C-reactive protein. Read about natural lipid-reducing agents as, alpha lipoic acid, artichoke extract, L-carnitine, chromium, conjugated linoleic acid, curcumin, DHEA, essential fatty acids, fiber, garlic, ginger, grapefruit pectin, gugulipid, hawthorn, niacin, pantethine, policosanol, polyenylphosphatidylcholine, soy protein, and tocotrienols in the Therapeutic Section of this protocol.

STRESS

More than a quarter-million heart episodes occur annually, i.e., palpitations, angina, arrhythmias, heart attacks, and strokes as a result of a stressful experience. This is particularly evidenced when an ailing heart, struggling to keep pace with circulatory demands, is forced to deal with emotional provocation. The journal Circulation reported that an individual who is prone to anger is about three times more likely to have a heart attack or sudden cardiac death than someone who is the least anger-prone. (Williams et al., 2000)

The journal Life Sciences offers an explanation for unfortunate end events. Higher levels of homocysteine are associated with feelings of aggression and rage, in both men and women. (Stoney et al., 2001) Individuals may be spurred into erratic behavior by metabolic processes gone awry. Modulation of homocysteine levels may allow a more docile individual to emerge, less cardiac risk prone from two perspectives. (Less homocysteine = less violent behavior = less cardiac disease.) An extensive review of homocysteine appears in the section devoted to Newer Risk Factors. Vitamins/minerals to maintain healthy levels are presented in the Therapeutic Section.

Type A individuals are, also, at a greater cardiovascular risk because their lives are dominated by self-imposed stress. Work expectations are driven by an unrelenting desire to achieve. An exaggerated sense of time urgency prompts accelerated locomotion and faster decision-making. Cynicism, hostility, and impatience, snuff out many personal relationships, denying the heart a much-needed rest from disharmony.

Under stress, the sympathetic nervous system is alerted and the release of adrenaline increases; ultimately, breathing, heartbeat, and blood pressure, also, increase. Cardiac patients are, often, prescribed beta-adrenergic blocking agents that calm the sympathetic nervous system, a gesture that asks a drug to succeed where attempts at lifestyle change may have failed.

Type D behavior, another variant having heart disease linkage, was recently described in the Lancet. (Denollet et al., 1996) Withheld and denied emotions, i.e., refusing to cry even when weeping is justified, and a lack of social connectedness (traits common to a type D personality) appear contributory to heart disease and stroke.

During periods of mental or emotional arousal, a silent ischemic attack (decreased supply of oxygenated blood) can occur. Though asymptomatic, severe heart damage may result. Unlike an angina attack, which is usually prompted by physical exertion, more than three fourths of silent ischemic attacks are caused by mental arousal. There is, also, a definite link between hardening of the carotid artery and higher levels of stress.

A recent study of 2800 men and women over 55 years of age showed that even minor depression can increase cardiac mortality by 60%, while major depression may actually triple the rate of cardiac-related death. (Penninx et al, 2001) There is, also, convincing evidence (published in ANZ J Surg) suggesting depression significantly increases the risk of mortality following myocardial infarctions and coronary bypass surgery. (Baker et al., 2001) Researchers explain the relationship between mind-set and mortality, pointing out the stress response to depression appears to trigger chronically high cortisol levels. Hormonal imbalances, in turn, can alter insulin resistance and increase blood pressure, magnifying the risks of a heart attack or surgery.

Stress protracts to so many traditional risk factors that emotions may be the dominant issue in coronary health. Note the following risk factors that share as their common bond, stress.

	Stress can destroy sound eating habits by the uncaring selection of inappropriate foodstuffs, eating hurriedly, or eating, not because of hunger, but as a respite from a dismal situation. Stress is a strong contributor to obesity, a factor in cardiovascular disease.
	Stress increases blood pressure. Studies involving 3000 Caucasians, suffering from depression and anxiety (ages 23 to 64) were found to have twice the risk of developing hypertension. The odds worsened for African-Americans, with the risk factor for hypertension increasing more than three times, during periods of unresolved stress. Even the companionship of a pet has been shown to reduce stress and the subsequent rise in blood pressure. (Relationship between psychological stress and coronary disease confirmed in journal Hypertension, (Hunyor, et al., 1997.)
	Stress makes blood glucose levels more difficult to control. Diabetes, a long-established risk to heart health, has been termed a disease fueled by emotions.
	Alternative Medical News reports that stress increases blood cholesterol levels. Students preparing for exams, Indianapolis 500 drivers (following the race), and accountants after the April 15th deadline show higher cholesterol levels. (Staff of Alternative Medical News, 1995)

HEREDITY

Scientific testing has advanced genetic screening far beyond compiling an oral history of ancestral successes and failures. Instead, geneticists are looking for mutated genes that may be expressing themselves, as contributors to coronary/artery disease. For example, 50% of suppressed HDL levels can be linked to genetic factors. A gene, ABC1, when mutated, appears responsible for increasing the risk of heart disease, by lowering levels of HDL cholesterol. Michael Hayden, professor of medical genetics at the University of British Columbia, reports that people with defects in ABC1 have just as much risk for heart disease because of too little HDL as individuals with high levels of LDL cholesterol.

The apoE4 variant of apoprotein E is the most well-defined genetic trait affecting poor LDL levels. A double allele, i.e., one apoE4 from each parent referred to as a double E4 genotype, reflects an increased prevalence of cardiovascular disease. Ronald Krauss, M.D., states that people with apoE4 have a tendency toward high blood cholesterol levels and increased heart disease risk. The apoE4 allele is very saturated fat sensitive, suggesting dietary manipulation may be of advantage to those with this genetic fault. In most cases, i.e., 90% or more of the population, modest dietary cholesterol has very little impact upon LDL cholesterol levels. (Bland, 2001) Moderate dietary cholesterol intake in apoE4 individuals can, however, lead to significant increases in plasma LDL levels. Bland challenges that public health recommendations do not address genotypes that alter dietary guidelines. Recommendations to universally avoid cholesterol-rich foods prevent some, who are not cholesterol sensitive, from eating a dietary that is a "pretty good food," as an egg.

Framingham researchers have found that a variation in the ACE (angiotensin converting enzyme) gene, apparently a sex-specific gene, may be an important contributor to high blood pressure in men. Men with the ACE variant have a 59% increased risk for developing hypertension.

Cardiac researchers at the University of California, San Diego School of Medicine have demonstrated that, in animal studies, the progression of heart failure can be completely arrested by inhibiting a single gene called phospholamban (PLB). This gene is a calcium-cycling gene, i.e., a gene that regulates the movement of calcium within heart muscle cells, promoting cardiac contractions. PLB acts as a brake on the calcium pump, increasing calcium storage so that it can be released on each heartbeat. The brake on the calcium pump is released by adrenaline, a sympathetic nervous system hormone; but, with a PLB failure, the balance between the accelerator and brake is disrupted. Either a heart attack or a genetic defect can cause the brake on the pump to be on too hard, thus restricting calcium and further weakening heart function. Cross breeding a mouse that is genetically engineered to develop heart failure with a mouse that lacks PLB produced an offspring with no signs of heart failure.

Dr. Paul Hopkins and researchers at the Cardiovascular Geriatrics Research Clinic in Salt Lake City, Utah, studied 266 patients with early coronary artery disease, all having a family history of early onset heart disease. They found high levels of homocysteine in this group, showing a connection between homocysteine and an inherited tendency to develop atherosclerosis.

Epidemiological evidence has shown homocysteine levels to be 45% lower in westernized adult black South Africans than in age-matched white adults, revealing racial genetic differences in homocysteine metabolism. (Vermaak et al., 1991) In fact, scientists at the Oregon Regional Primate Research Center theorize that refractory hyperhomocysteinemia may best be explained by disrupted gene expression. For example, about one half of individuals with hyperhomocysteinemia respond favorably to higher doses of vitamin B6, due to an inborn cystathionine synthase deficiency; others have a genetic deficiency of methylenetetrahydrofolate reductase (MTHFR). (Mudd et al., 1972)

A study reported in Nature Structural Biology showed that folates, derivatives of folic acid, work by activating MTHFR. (Guenther et al., 1999) MTHFR participates in homocysteine control by producing methyltetrahydrofolate, a compound that plays an important role in regulating blood homocysteine levels. Individuals with a mutation in the MTHFR gene lack the ability to convert folic acid into 5-methyltetrahydrofolate, an active contributor in the methyl donation pathway of the folate cycle. (James et al., 1999) Disruption of this cycle represents the domino effect (when one system fails to perform, others downstream suffer as well). In this case, homocysteine clearance is disrupted and hyperhomocysteinemia, a powerful endangerment to cardiac health, results. The genetic flaw is correctable by administering 5-methyltetrahydrofolate supplements, the principal circulating folate, to unlock the metabolic block. (Sagar et al., 2001) (Folinic acid (5-formylTHF) is available as calcium folinate (also know as leucovorin calcium) an immediate precursor to 5,10 methylenetetrahydrofolate.)

According to researchers reporting in the American Journal of Physiology, about 50% of individuals who are insulin resistant have the condition because of an inherited propensity. (Bogardus, et al., 1985) The other 50% fall victim because of lifestyle demerits, i.e., a lack of physical fitness, poor dietary selections, and obesity.

Approximately 32 million Americans are carriers for hemochromatosis, or iron overload. Hemochromatosis is predominantly a genetic disease reflecting abnormal iron metabolism. The gene responsible for hemochromatosis was identified in 1991 and contributes to excessive iron retention despite eating an ordinary diet. Small numbers of individuals with hemochromatosis acquire the condition through massive doses of iron supplements or blood transfusions, but the genetic form is most common. To learn more about hemochromatosis, consult Iron Overload, appearing in this section (Traditional Risk Factors).

Arteriosclerosis, Thrombosis and Vascular Biology reported that carotid plaque was significantly more common in both men and women whose parents died prematurely of coronary heart disease (CHD) than in subjects with no familial history of premature death from CHD. (Zureik et al., 1999)

Genetic factors can influence obesity and blood lipids. Laval University in Quebec, Canada determined that pairs of identical twins, overfed by the same amount of calories, showed nearly identical weight gain, body fat, and lipid levels. Comparisons of nonrelatives, participating in the study, showed little similarity.

GENDER

Cardiovascular disease, at one time, was considered to be, predominantly, a disease affecting men, not women. Statistics do not support this logic, for studies have demonstrated that heart disease is the number one killer for both men and women. Of the 1.1 million heart attacks reported annually, about 500,000 occur among women.

The Framingham Study reported findings involving 5,209 participants, 2,873 of whom were women. Results of the study follow:

	In both men and women, coronary heart disease has exceeded that of other cardiovascular illnesses, such as stroke or congestive heart failure.
	While coronary events occurred twice as often in men, with advancing age, the incidence of heart disease in women approaches that seen in men. Menopause appears the interval associated with a significant rise in coronary events, as well as a shift to more serious manifestations of the disease.
	The New England Journal of Medicine reported that hormone replacement therapy (HRT) in menopausal women with angiographic-determined heart disease did not lower the progression of the disease. (Nabulsi, 1993) New guidelines, issued by the American Heart Association, agreed that women with cardiovascular disease should not be given HRT for the sole purpose of preventing future heart attacks. HRT, in fact, raised the risk of recurrent attack and death during the first year of usage, and thereafter lowered it only slightly. (Mosca et al., 2001) Though estrogen replacement therapy may be helpful in lowering refractory lipoprotein(a) and high fibrinogen levels, it increases C-reactive protein levels, making its benefit an apparent stand off.
	Coronary heart disease manifests itself differently in men and women. In women, angina was the most common initial symptom, whereas in men, myocardial infarction was the most frequent first coronary symptom.
	High triglycerides were more predictive of eventual heart disease in women than in men. Elevations in C-reactive protein are, however, the single strongest predictor of future vascular risk, according to the Women's Health Study. Women with the highest levels of C-reactive protein in their blood had a five-fold increased risk of future cardiovascular disease and a sevenfold increase in heart attack, compared to those with low levels.
	When heart attack was the first coronary event, nearly half were unrecognized in women, compared to only 1/3 undetected in men.
	Only 56% of women suffering a heart attack can expect to live another year, compared to 73% of male victims. Twenty-seven percent of men who have a heart attack will likely have a second attack within six years, compared to 31% of women.
	Diabetes was a particularly potent coronary risk factor in women.
	While many studies have demonstrated that men who are active tend to live longer, it has never been clear that the same is true for women. Men had a clear exercise-response curve, with greater activity more effective than moderate. The women in the most active group had a higher rate of heart disease and mortality than did those in the moderately active group. An increased risk of sudden cardiac death in the more active women, demonstrates that the level of the exercise must match the strength and metabolic type of the participant.

SEDENTARY LIFESTYLE

Scientists believe that a properly planned exercise program may be the single greatest preventive against cardiovascular disease (CVD). It is extremely important, however, that the individual and the activity be properly matched. Even among young athletes, intense but sporadic exercise, actually, increases the risk of a fatal heart attack. A singles tennis match, in an unprepared participant, increases the risk of heart attack sixfold.

The exercise level need not be unpleasantly aggressive to be beneficial. In the past, it was thought that an individual, using exercise as a cardiovascular protective, should select an activity that produced a state of breathlessness and participate in the action several times a week. It has now been determined that cardiovascular strengthening can be obtained from low-intensity activity, such as walking for 30 minutes, either daily or every other day. In fact, Dr. Shah Ebrahim, a British cardiologist, states that sexually active men, i.e., those engaging in sex three or four times a week halve their risk of either a stroke or a heart attack. Some researchers question whether the mild to moderate energy expended during intercourse is the perk favoring a healthier cardiovascular system or if it is the mind-set that drives the sexual act.

The New England Journal of Medicine reported findings involving 180 postmenopausal women (45 to 64 years) and 197 men (30 to 64 years). (Stefanick et al., 1998) The participants were divided into 4 groups: diet-plus exercise, diet alone, exercise alone, and controls. LDL cholesterol levels in the diet-plus exercise group were, significantly, reduced compared to the three remaining groups. It is, also, possible that exercise will alter the size of LDL particles, making them larger and less dense. (Recall that abnormally small LDL particles are highly susceptible to oxidation and elude standard testing processes, misrepresenting end results.)

Exercise reduces blood pressure and heart rate by quieting the sympathetic nervous system. As epinephrine (adrenaline) secretion decreases, blood pressure and heart rate also decrease. Consequently, statistics support that a regular exercise program reduces the risk of stroke, not only by lowering blood pressure but also by increasing peripheral circulation and oxygen delivery. These findings were confirmed in a 10-year study, involving 114,000 deaths occurring among Norwegian women. All of the women entered the study stroke free, but only the middle-aged to elderly women, who were physically active, retained their stroke-free status. (Ellekjaer et al., 2000)

Excessive fibrinogen, a risk factor for cardiovascular disease, is impacted by exercise. A study has shown that exercise of moderate intensity increases fibrinolytic activity, by increasing tissue plasminogen activators. (Tissue plasminogen activators break down fibrinogen, decreasing the risk of blood clot formation.) Substantiation of this process occurred when 14 sedentary men (average age 35) and 12 men who were regularly active (average age 35) participated in exercise sessions, morning and evening, at 50% maximal oxygen consumption. The results of the study indicated that moderate intensity exercise increased the activity of tissue plasminogen activators in both physically active and sedentary men, particularly during evening exercise. C-reactive protein, another of the newer risk factors for cardiovascular disease, also, appears lowered by exercise.

A sedentary lifestyle encourages weight gain and worsens Syndrome X, a condition of insulin resistance and compensatory hyperinsulinemia (insulin excess). Conversely, physical fitness increases cellular glucose responsiveness by as much as 25% and decreases the amount of insulin secreted after a carbohydrate load. Exercise makes the vasculature less prone to damage when insulin levels are unstable. Vulnerabilities associated with Syndrome X, i.e., diabetes, hypertension, hypertriglyceridemia, and suppressed HDL levels are, often, modifiable by exercise-induced weight loss.

If CVD has already manifested, a monitored exercise program can assist in recovery. Exercise helps in building a new network of blood vessels, naturally bypassing those impaired. The conclusion regarding exercise is that it is never too late to reap the benefits from a properly structured program. According to the Framingham Heart Study, only recent exercise, however, makes a significant difference. Exercise undertaken earlier in life showed no sustained cardio-protection.

Even low-intensity exercise can be a harbinger of free radicals; over exercising can generate enough free radials to damage the DNA in white blood cells. The remedy is to provide the system with adequate amounts of antioxidants before engaging in physical activity. Also, sweating during exercise can drastically deplete minerals. This phenomenon likely contributes to the numbers of sudden deaths occurring among athletes and joggers. Lost body fluids and minerals should be replaced immediately.

Having extolled the virtues of a properly planned exercise program, it is quite all right to enjoy an afternoon nap, as well. A recent Greek study found that men who regularly took a half-hour nap had a 30% lower risk of having a heart attack; men who rested for an hour reduced their risk by 50%.

GUM DISEASE

Researchers are examining the role of gum disease in the genesis and progression of heart disease. The inflammatory process, observed in the lining of atherosclerotic blood vessels, appears to be paralleling chronic inflammation observed in periodontal disease. Findings reported in the American Journal of Epidemiology showed that fibrinogen and C-reactive protein (coagulability and inflammatory markers) are increased in individuals with periodontal disease. (Wu et al., 2000) Dr. Tiejian Wu and colleagues at State University of New York reported that gum disease might, also, be related to hypercholesterolemia, though a weaker link is found between elevated cholesterol and gum disease than for elevations in C-reactive protein and fibrinogen.

Bleeding, red, swollen gums are depictive of gingivitis, a condition of inflammation and bone deterioration, promulgated by bacteria. Researchers at the University of Buffalo, New York School of Dental Medicine have determined that the bacteria, B. forsythus, P. gingivalus, and C. recta (oral pathogens) can inflict cardiac damage. Dr. Robert Genco found that the increased risk of heart problems in individuals with one or more of these bacteria was from 200-300%. Infection and Immunity, also, incriminated Eikenella corrodens and Prevotella intermedia as strains of bacteria capable of invading coronary artery cells. (Dorn et al, 1999) A study, involving 10,000 adults, concluded that periodontal disease should be regarded as a valid marker, for either frank or eventual heart disease.

Should the gums be pulling away from the teeth and appear red, swollen, or tender, seek immediate dental care. Other red flags are gums that bleed while brushing, a bad breath, or a discharge of pus. Turn to calcium, coenzyme Q10, and vitamin C in the Therapeutic Section to read about maintaining healthy gum tissue and avoiding periodontal disease.

HYPOTHYROIDISM (Low Thyroid Function)

Seldom considered but often the source of disease, the thyroid gland, a member of the endocrine system, should be evaluated in all cardiac patients. A healthy thyroid gland benefits the heart by influencing weight, reducing depression, and modulating cholesterol and homocysteine levels. Hypothyroidism impairs methionine metabolism, a key process in homocysteine control.

Researchers measured levels of homocysteine and cholesterol in 7000 individuals from a general U.S. population. (Morris et al., 2001) The 7000 were then subdivided into two groups: those with hypothyroidism and those with normal thyroid function. Those who tested positive for hypothyroidism (reference range for high sensitivity TSH testing is 0.34-5.00mIU/mL) were more likely to be white, female, and slightly older.

About two-thirds of those diagnosed with hypothyroidism had cholesterol levels nearly four times greater than normal. Approximately 50% of those thyroid impaired had high homocysteine levels, compared to 18% of people in the general population. It is estimated that about 90% of hypothyroid subjects in the U.S. population are either hypercholesterolemic or hyperhomocysteinemic as compared with only 31% of individuals with normal thyroid function.

A 5-year study involving 347 patients (reported in the Journal American Geriatric Society) evaluated the effects of thyroid therapy upon atherosclerosis. (Wren, 1968) One hundred thirty two individuals suffering from heart attack, stroke, angina pectoris or disruption in peripheral circulation (mean age 64.5 years) were among the patients enrolled in the study. Two hundred and fifteen of the 347 participants (mean age 54.7 years) were asymptomatic but considered high risks because of the presence of electrocardiographic abnormalities, hypertension, diabetes or hypercholesterolemia. Only 9% of the patients (31 of the total 347) tested positive for hypothyroid conditions. Nonetheless, all were treated with thyroid extract, and substantial clinical improvements occurred in a number of the patients. Of the 132 symptomatic patients, 29 out of 41 with angina reported benefits that included increased exercise tolerance, decreased frequency and severity of attacks, and less need for nitroglycerin. Mean cholesterol levels fell by 22%. Eleven patients died during the 5-year study, less than half of the expected rate based on U.S. Life Tables.

How might poor thyroid function contribute to arteriosclerotic vascular disease, i.e., hardening of the arteries? Researchers speculate that hypothyroidism may slow or decrease the metabolic breakdown of fats like cholesterol. It may also impair kidney function and interfere with the activity of an enzyme, methylenetetrahydrofolate reductase that the body depends upon to process (remethylate) homocysteine.

In addition, the Journal Card Fail reported that if the body fails to convert thyroxine (T4) to triiodothyronine (T3), the body's most potent thyroid hormone, T3 becomes less available in the bloodstream, while levels of reverse T3 (rT3), an inactive metabolite of T3, tends to build up. (Shanoudy et al., 2001) A low T3/rT3 ratio is associated with a weakened ability of the left ventricle to pump blood and is highly predictive of poorer short-term outcome in patients with severe chronic heart failure.

Illustrative of the value of a healthy thyroid gland, the National Health and Nutrition Examination Survey showed that once the thyroid falters in its performance, the heart may not be far behind. (Valuable information regarding the thyroid gland is contained in the Therapeutic Section under soy protein.)

IRON OVERLOAD (Hemochromatosis)

Research to determine the effects of dietary iron on cardiovascular disease (CVD) have had mixed findings. Annals of Epidemiology reported that no association between iron levels and mortality from CVD was found in data collected from NHANES II and the National Death Index. (Sempos et al., 2000) The Journal of the American Heart Association chronicled an opposing view, reporting that free iron corresponds to a greater risk of heart disease by encouraging free radical production. (Stefan et al., 1997) The warning extended to exclude supplemental iron and foodstuffs containing high concentrations of iron. Data published in the American Journal of Epidemiology confirmed that excessive amounts of heme iron increased the risk of fatal myocardial infarctions. (Klipstein-Grobusch et al., 1999)

Hemochromatosis causes severe depletion of liver glutathione, an extremely important antioxidant. As glutathione is depleted, free radical damage becomes even more aggressive. The increase in free radical activity in brain cells can increase stroke progression. Stroke patients with high blood ferritin (a measurement of the total iron stored in the body), showed greater post stroke trauma, i.e., increased lethargy, aphasia, and unawareness.

Several studies have found that iron overload is most damaging to the heart if LDL cholesterol levels are, also, high. Free iron oxidizes LDL cholesterol; oxidized LDL cholesterol, markedly, increases the damage imposed upon the cardiovascular system. Understanding Normal and Clinical Nutrition reported that every 1% rise in blood iron increases the risk of heart disease by 4%. (Whitney et al., 1998)

High iron levels affect endothelial function by interfering with nitric oxide activity, a vasodilating, lipid lowering, and anti-platelet aggregating factor. When 10 healthy volunteers were injected with high doses of iron (0.7 mg/kg body weight), malondialdehyde (a marker for peroxidized polyunsaturated lipids) increased and the functionality of the endothelium was altered.

Just as the iron in your car can rust, the iron in your body is susceptible to rust, or oxidation, a process that damages tissues and blood vessel walls. Dr. Hidehiro Matsuoka, of Kurume Medical School in Japan, says that people should watch their intake of iron with the same commitment that they watch cholesterol levels. This means being checked regularly for high iron levels, if over 40 years of age and displaying other risk factors for heart disease. Optimal iron levels appear to be <100 mcg/dL, though the standard reference range is up to 180 mg/dL.

Tests such as total iron binding capacity, serum iron, and a DNA test called HLA-H along with family history are other excellent screening tools for hemochromatosis. Determining iron status is extremely important, for if untreated, iron overload becomes a strong contributor to atherosclerosis, irregular heartbeat, heart attack, or heart failure. Iron-induced cardiac irregularities can affect both young and senior subjects, even anemic individuals.

An individual with iron overload is frequently advised to avoid foods rich in vitamin C or vitamin C supplements because of the iron enhancing factors associated with the nutrient. (Many individuals with hemochromatosis can, however, use 500 mg of buffered vitamin C 3 times per day between meals.) Cast-iron cookware and iron-fortified foodstuffs should be avoided, and meats and alcohol restricted. On the other hand, coffee and tea consumed with meals assist in blocking iron absorption from foods. Fruits (non-ascorbic acid varieties) and vegetables are excellent dietary choices. Simply withdrawing iron fortified foods from the diet can prompt dramatic changes in iron levels.

Dispersed throughout the therapeutic section are supplemental suggestions to reduce iron overload, as calcium, fiber, garlic, magnesium, vitamin E, and green tea, but individuals wishing to protect themselves from iron buildup may, also, want to consider a blood donation. Some individuals denote the blood to themselves to ensure a healthy future supply, but this course is only valuable if the individual is not anemic. Should anemia coexist with hemochromatosis, drugs in the form of iron chelators may be prescribed.

It is important to note that adequate amounts of iron are absolutely essential to good health, but using iron supplements or iron fortified foods are not recommended for men or postmenopausal women, unless diagnosed with an iron deficiency. It is judged that approximately one out of every 200 people actually have iron overload disease. Read the sections devoted to Heredity and Chelation Therapy in this protocol to learn more about hemochromatosis.

NEWER RISK FACTORS

In the last 25 years, the incidence of coronary fatalities has decreased by 33%. This is due largely to adherence to traditional risk factors. Dr. Paul M. Ridker, M.D., M.P.H., Director of Cardiovascular Research, at Brigham and Women's Hospital, Boston, Massachusetts speculates that an auxiliary list of newer predictive factors may increase the numbers benefiting from 21st Century diagnostics and treatment. (See Figure 3)

FIBRINOGEN

Fibrinogen is a blood protein that plays a critical role in normal and abnormal clot formation, a mechanism referred to as coagulation. A process of checks and balances, i.e., an interaction between clotting factors and naturally occurring anticoagulants, normally results in healthy levels of fibrinogen and normal coagulation. If, however, fibrinogen levels increase above normal, a blood clot becomes a threat; if fibrinogen levels decrease below normal, a hemorrhage can result. Though the reference range used by most laboratories is 150-460 mg/dL, it is crucial to keep serum fibrinogen under 300 mg/dL, a level considered safe.

The coagulation of blood depends upon a number of proteins found in plasma called clotting factors. Normally, clotting factors are inactive, but following injury, they become activated. Exposed collagen or chemicals released from injured tissues initiates a series of chemical reactions that results in the production of prothrombin activators. Prothrombin activators convert prothrombin to thrombin, which in turn converts fibrinogen into fibrin. This network of protein fibers traps blood cells, bloodstream infiltrates, and platelets producing a clot.

Platelets, the smallest of blood elements, are absolutely essential in sealing vascular injuries, whether caused by a knife wound or hypertension. According to Dr. James Braly M.D., as long as the interior of the vessel is smooth, platelets are not summoned into service; but if trauma is detected, platelets rush to the site, forming a plug to repair the wound. Once activated, platelets do more than provide the materials for vascular repair. They, also, release serotonin (a vasoconstrictor) and the powerful platelet aggregator thromboxane A2. Abnormal platelet stickiness increases atherosclerosis and further narrows the arteries, preliminaries to most strokes and heart attacks. Fibrinogen promotes the negative activity of platelets by encouraging their binding together, a sequence common to a deadly blood clot.

About 700,000 heart attack and stroke deaths occur each year in the U.S., as a result of a blood clot obstructing the delivery of blood to the heart or the brain. This occurs, in part, because fibrinogen combines well with LDL cholesterol, initiating plaque formation. If fibrinogen is then converted to fibrin (a protein having the nature of barbed wire), other bloodstream infiltrates can become entrapped in the tangle. From this mesh, emerges an atheromatous tumor, capable of continued growth until full occlusion occurs. Closure represents only part of the risk, for plaque is highly susceptible to breakage and clot formation.

Fibrinogen, also, plays a role in monocyte adhesion and smooth muscle proliferation, adding to the likelihood of vascular closure. Reports published in the New England Journal of Medicine showed that those with high levels of fibrinogen were more than twice as likely to die of a heart attack. (Wilhelmsen et al., 1984)

The Life Extension Foundation (LEF) was the first research group to recognize the importance of assessing fibrinogen as an independent risk factor for cardiovascular disease. A study in the Journal of the American College of Cardiology corroborated LEF's position on fibrinogen, when nearly 400 male physicians participated in the Physicians' Health Study. (Jing et al., 1999) Blood fibrinogen levels of 199 subjects, who experienced heart attacks during the study period, were compared with those of 199 control subjects who did not suffer heart attacks. Individuals having heart attacks had significantly higher fibrinogen levels compared with those physicians with healthy fibrinogen levels. Several studies have shown a stronger association between cardiovascular deaths and fibrinogen levels than for cholesterol.

A study, involving 3043 patients with angina pectoris who underwent coronary angiography and were followed for 2 years thereafter, concluded that higher base-line levels of fibrinogen was an independent predictor of an increased incidence of myocardial infarction or sudden death. In contrast, coronary risk was low among patients with low fibrinogen concentrations despite increased serum cholesterol levels. (Thompson et al., 1995)

Aortic stenosis is the abnormal narrowing of the valve between the left ventricle and the aorta. The narrowing or stenosis is, often, associated with calcification, a process that may involve fibrinogen. Fibrinogen appears to have an attraction for calcium; as fibrinogen and calcium unite, the valvular diameter becomes smaller.

Various factors influence plasma fibrinogen levels. For example:

	Homocysteine, by inhibiting the production of tissue plasminogen activators, a substance that breaks down fibrinogen, contributes to fibrinogen excesses.
	Fibrinolysis and Proteolysis reported that increased winter cardiovascular mortality is related to a cold weather increase in fibrinogen concentrations. (Exposure to cold increases fibrinogen levels by about 23%.) (Khaw et al., 1997)
	Smokers and sedentary people have higher levels of fibrinogen.
	Nutrient depletion can retard fibrinolysis and increase fibrinogen levels.
	Infections tend to increase fibrinogen levels.
	Estrogen replacement therapy appears to attenuate normal age-related increases in fibrinogen, while Lopid (gemfibrozil) increases fibrinogen by 9% to 21%.

Unfortunately, pharmaceutical drugs have not been of significant value in reducing fibrinogen levels. Initial data suggested that Bezafibrate, a European drug, reduced fibrinogen levels in patients with established coronary heart disease. The Bezafibrate Infarction Prevention Study yielded disappointing results, however, with no significant evidence of efficacy in lowering fibrinogen.

Anticoagulant therapy usually becomes the treatment of choice to reduce fibrin. Warfarin (Coumadin) and heparin are, often, prescribed, but it is, difficult to administer enough of an anticoagulant to lessen the risk of a blood clot without increasing the risk of a hemorrhage. Dispersed throughout the Therapeutic Section are natural products with either fibrinolytic or platelet aggregation inhibiting activity as, aspirin, bromelain, curcumin, essential fatty acids, garlic, ginger, ginkgo biloba, green tea, gugulipid, niacin, pantethine, policosanol, proanthocyanidins, vitamin A and beta-carotene, vitamin C, vitamin E, and homocysteine-lowering nutrients. (Recall that homocysteine, by inhibiting the production of tissue plasminogen activators, contributes to fibrinogen excesses.)

To read more about fibrinogen, consult the sections entitled Obesity, Sedentary Lifestyle, Gum Disease, and Fibrinolytic Activity, Introduction to Homocysteine, and Link Between Infection and Inflammation In Heart Disease contained in this protocol.

FIBRINOLYTIC ACTIVITY

Balance between tissue plasminogen activators (t-PA) and plasminogen inhibitors (PAI-1) controls activity of the fibrinolytic system in healthy individuals. If the fibrinolytic process is impaired, individuals can be classed as either hemorrhage or thrombosis prone. Generally, an increased PAI-1 concentration reflects impairment of the fibrinolytic process, with a reduction in plasmin formation and an accumulation of fibrin, platelets, minerals, and lipids. This model can predispose recurrent thrombosis. Recent data from studies of both animals and humans indicate that PAI-1 is preferentially produced in visceral adipose tissue, a finding that explains the hypercoagulability associated with obesity. In patients with PAI-1 deficiencies, a hemorrhage may be a concern.

The N Engl J Med reported that anomalies occurring in t-PA and PAI-1 are likely to be critical factors underlying hyperinsulinemia in ischemic heart disease. (Despres, et al., 1996) Barry Sears, Ph.D., believes scientific evidence has, rightly, exposed hyperinsulinemia as an indicator of an eventual heart attack. Hyperinsulinemia bestows some of its coronary damage by increasing the risk of hypertension (twofold), hypertriglyceridemia (three to fourfold), type 2-diabetes (five to six fold), and diminishing HDL levels. Impaired fibrinolytic activity appears to be a contributor in this sequence.

Though blood clots loom as one of the dominant factors in cardiovascular disease, the selection of supplements that favors fibrinolysis and discourages platelet aggregation should be done sensibly. It is possible that the cumulative value of nutrients with similar intent, i.e., blood thinners and anti-fibrinogens, could, significantly, overcorrect a condition, particularly if used in concert with prescribed blood thinners.

The Lancet reported that asymptomatic patients on warfarin, a blood thinning therapy, should consider low-dose vitamin K if blood-clotting time, as measured by the international normalized ratio (INR), is between 4.5 and 10.0. (Crowther et al., 2000) Follow-up studies to determine the success of vitamin K therapy (1 mg/day) showed that 4% of the patients who received vitamin K therapy had bleeding episodes, compared with 17% of those in the placebo group. The conclusion of the study was that low dose Vitamin K, an inexpensive intervention without known toxicity, might prevent a hemorrhage in patients on warfarin therapy.

Research suggests that many peripheral factors influence the clotting of blood. For example, The Lancet reported that air travel increases the risk of venous thrombosis, by increasing prothrombin factors. (Scurr et al., 2000) Note: Venous thrombosis is a condition characterized by a blood clot in a non-inflamed vessel. Pain, swelling, and inflammation may follow if the vein is significantly occluded. Prothrombin is an intermediate factor in the coagulation process.

LIPOPROTEIN(a)…Lp(a)

Peak time for a heart attack appears to be between 6:00 AM and 12:00 noon. Heart attacks occurring during these hours are thought to cause more heart damage than those occurring at other times of the day. The "why" is deeply concerning to the medical community. Some theorize that facing the challenges and urgencies of a new day, could be activating the sympathetic nervous system. Was the "fight or flight" mentality too much stimulus for a cardiac-prone individual?

Japanese researchers took the question further and measured serum lipids and clotting factors in two groups of men: those who suffered a heart attack during the 6-hour morning "peak period" and those who had a heart attack at other times during the day or night. (Fujino et al., 2001) Morning heart attack victims were found to have significantly higher levels of Lp(a), the only distinguishable factor compared to the other group. There was, also, a tendency toward hypercoagulation, increasing the risk for developing a life-threatening thrombus or clot. The conclusion of the Japanese study was that increases in Lp(a) appear to be influencing coagulation factors involved in the occurrence of morning heart attacks.

The physical character of Lp(a) adds to its complexities. It has a lipoprotein structure, nearly identical to LDL cholesterol. A variation occurs when a disulfide bond attaches Apo(a), a protein having the nature of plasminogen, to the lipoprotein. LDL + Apo(a) = Lp(a). Plasminogen is an inactive plasma protein that is converted to its active form, plasmin (also called fibrinolysin), an agent capable of dissolving fibrin.

Because of similar structure, it is theorized that Lp(a) competes for plasminogen that binds to fibrin and the surface of endothelial cells, inhibiting the break down of fibrin. Thus it appears that Lp(a) alters fibrinolysis (the breakdown of fibrin) occurring at the cell surface and inhibits plasminogen binding to fibrin. The end result is a greater risk of blood clot formation. (Loscalzo et al., 1990)

Complicating the atherosclerotic/Lp(a) mechanism, Apo(a) has a sticky, Velcro nature, causing it to easily tie up in blood vessels. Apo(a)'s adhesiveness provides an ideal trap for LDL, VLDL, and other bloodstream infiltrates, as calcium. In layered fashion, circulating materials mount the debris, promoting the growth of an atheromatous tumor. As plaque accumulates, greater amounts of Lp(a) are observed at the site of the occlusion. Recent studies also incriminated lipoprotein(a) in angina pectoris, sighting accumulations of Lp(a) in the plaque of unstable angina patients.

The risk of a major coronary event nearly tripled among middle-aged men participating in a Lp(a)/heart study, whose Lp(a) levels fell within the highest 20% of the study group compared to those with lower levels. (VonEchardstein et al., 2001) The risks escalate even higher if Lp(a) coexists with high LDL cholesterol, low HDL cholesterol, and hypertension. Investigators, also, noted elevated Lp(a), i.e., above 30 mg/dL in 20% of all thromboembolism patients, compared to 7% of healthy controls. Lp(a) may prove to be one of the most predictive of the risk factors for strokes, restenosis (recurrent narrowing of a vessel), or heart attack following either coronary bypass surgery or angioplasty.

Plaque formation is an essential response to vascular injury. When a blood vessel has been damaged, repair is paramount. If benign materials are available, as vitamin C, to protect the vessel from injury and to participate in vascular repair, the need for Lp(a) is moot. Without adequate amounts of vitamin C, Lp(a) becomes indispensable.

There is a vast difference between materials used to repair vascular injuries. For example, vitamin C repairs the wound, leaving the vessel wall smooth but stronger; Lp(a) repairs the injury, leaving residual trappings, i.e., a sticky compress, capable of continued growth. Although Lp(a) has an important function in the body, Matthias Rath, M.D., considers Lp(a) 10 times more dangerous than LDL cholesterol.

Aortic stenosis, the narrowing of the valve separating the left ventricle from the aorta, is often described as a calcification process. Lp(a) appears to play a role in this process as deposition of Lp(a) on the aortic valve creates a binding site for calcium. Please consult the section devoted to valvular disease, for an in-depth discussion, relating to aortic stenosis.

The reference interval for Lp(a) is 0-30 mg/dL. Reference ranges are only valuable as generic markers. Depending upon the test, risk may be, significantly, increased as values reach upper or lower limits of normal.

Read about essential fatty acids, niacin, vitamin A, and vitamin C (nutrients that assist in maintaining healthy levels of lipoprotein(a)) in the Therapeutic Section of this material. Introduction to Homocysteine (below) provides additional information relating to Lp(a).

Introduction to HOMOCYSTEINE

(Consult Homocysteine Lowering Nutrients and Elimination Pathways in the Therapeutic Section for a discussion relating to detoxification mechanisms and nutrients to reduce homocysteine levels.)

Homocysteine, a sulfur containing amino acid, is in the forefront as a cardiovascular risk factor. Though its role in atherosclerosis and atherothrombosis is confirmed, it should be noted that most naturally occurring substances have purpose in physiology; homocysteine is not the exception.

The American Academy of Family Physicians explains that homocysteine is normally changed into other amino acids for use in the body's normal functions. For example, homocysteine is an intermediate in the biosynthesis of L-cysteine, a non-essential amino acid and metabolic precursor to cystine. Cysteine is important in fatty acid synthesis and energy metabolism, but its most important role takes place in the liver where it assists glutathione in the detoxification of carcinogens and dangerous chemicals. (Braverman, 1987) Once cysteine is generated, it can be directed into several pathways, including synthesis of glutathione and taurine. Amino acids play strategic roles in cardiac function, cholesterol excretion, and bile salt formation. (Lehninger et al., 1993) Because the intermediate metabolite, homocysteine, is located in a critical metabolic crossroad, it either directly or indirectly impacts all methyl and sulfur group metabolism occurring in the body. (Miller, et al., 1997)

Some researchers believe that the residuals of homocysteine may support the adrenal glands, contribute to neurotransmitter synthesis and the regeneration of bones and cartilage. It should be strongly emphasized that homocysteine must be detoxified in order for its by-products to offer bio-chemical advantage. If disposal systems (remethylation and transsulfuration) are nonfunctional, allowing homocysteine to accumulate, the results can be deadly. Remethylation and transsulfuration are discussed in detail in the Therapeutic Section of this protocol under Homocysteine Lowering Nutrients and Elimination Pathways.

Experiments have demonstrated if high levels of homocysteine accumulate in the cell, all methylation reactions are completely inhibited. (Duerre et al., 1981) Because methylation is used for so many body processes apart from homocysteine metabolism, if this system becomes less functional, multiple negatives can occur. For example, methylation is fundamental to maintaining healthy DNA; without DNA repair, mutations and strand breaks occur. Also, the liver depends upon methylation to perform the rites of detoxification. Nutrients considered methylation enhancers are vitamin B12, folic acid, zinc, trimethylglycine, choline, and vitamin B6. (Vitamin B6 is of particular importance if the diet emphasizes methionine-rich foods, i.e., animal products.)

If homocysteine is not detoxified and begins to accumulate, plaque builds up in the endothelial cells lining the arteries. This occurs as homocysteine reacts with LDL to form small, dense particles. Macrophages use these particles to form foam cells, that historically like to "swell," protruding into the space of the artery, obstructing blood flow. Elevated levels of homocysteine, also, block production of nitric oxide in the cells of the blood vessel walls, making the vessels less pliable and even more susceptible to plaque buildup. Dr. Kilmer McCully, crusader for the homocysteine theory of heart disease, says that homocysteine plays a key role in every pathophysiological process that leads to arteriosclerotic plaque. (McCully, 1996)

The Journal Clin Invest reported that homocysteine facilitates the generation of hydrogen peroxide. By creating oxidative damage to LDL cholesterol and endothelial cell membranes, hydrogen peroxide can then catalyze injury to vascular endothelium. (Starkebaum G et al., 1986) Stamler et al., 1993) Nitric oxide, released by endothelial cells (also known as endothelium-derived relaxing factor), protects endothelial cells from damage by reacting with homocysteine, forming S-nitrosohomocysteine, which inhibits hydrogen peroxide formation. However, as homocysteine levels increase, this protective mechanism can become overloaded, allowing damage to endothelial cells to occur. (Stamler et al., 1992) (Stamler et al., 1996)

A heart attack or stroke is more likely to occur as homocysteine inhibits the production of tissue plasminogen activators (a substance produced naturally by cells in the walls of blood vessels that breaks down fibrinogen). Thromboxane A2, a pro-platelet aggregating compound, increases, as well as the binding of Lp(a) to atheromatous materials. Blood flow, as demonstrated by numerous studies, is significantly impaired, particularly among middle aged and senior subjects with high levels of homocysteine.

The European Journal of Clinical Investigation reported that 40% of all stroke victims have elevated homocysteine levels compared to only 6% of controls. (Brattstrom et al., 1992) Other studies chronicled similar findings, i.e., elevations in homocysteine in 16 out of 38 patients with cerebrovascular disease (42%), 7 of 25 with peripheral vascular disease (28%), and 18 of 60 with coronary vascular disease (30%), but in none of the 27 normal subjects. (Clarke et al., 1991) A team from Massachusetts General reported even more incriminating data, announcing that mild-moderate hyperhomocysteinemia independently increased the risk of stroke by 86%. (Results collected through meta-analysis of 15 studies and reported by Kelly, 2001) High concentrations of homocysteine and low levels of folate and vitamin B6 are, also, associated with an increased risk of extracranial carotid-artery stenosis in the elderly. (Selhub et al., 1995) Higher levels of homocysteine predispose deep venous thrombosis, as well. (den Heijer et al., 1996)

Because homocysteine encourages free radical activity, genes are also involved in the homocysteine attack. This has significant impact upon the cardiovascular system, as homocysteine activates genes in blood vessels, encouraging the coagulation process and the proliferation of smooth muscles. Since homocysteine wields such a powerful cardiovascular blow from so many different directions, it is estimated that a 3-unit increase in homocysteine equates to a 35% increase in heart attack risk. (Verhoef et al., 1996) The risk becomes even greater if hyperhomocysteinemia occurs with other risk factors. For example, a hypertensive woman with elevated homocysteine levels has a 25-fold increased risk of vascular disease.

Though the dangers imposed by hyperhomocysteinemia are not a new find, most of the medical community has (until recently) ignored homocysteine, as a cardiovascular risk. Decades ago, Dr. Kilmer McCully, M.D., pioneered the homocysteine/cardiovascular hypothesis; the Life Extension Foundation focused upon the dangers of homocysteine and outlined a vitamin protocol to reduce hyperhomocysteinemia in an article released in Nov. 1981 (Anti-Aging News pp 85-86). Eric Braverman, M.D., joined the crusade, describing homocysteine as a substance worse then cholesterol. Homocysteine is regarded as more dangerous than cholesterol because homocysteine damages the artery and then oxidizes cholesterol before cholesterol infiltrates the vessel.

Craig Cooney, Ph.D., says that excessive homocysteine is now widely recognized by scientists, as the single greatest biochemical risk factor for heart disease, estimating that homocysteine may be a participant in 90% of cardiovascular problems. While cholesterol does not, normally, pose a cardiac risk until levels exceed 240 mg/dL, some researchers consider homocysteine so capricious that even so called "normal" levels may contribute to heart disease.

Homocysteine levels should be kept as low as possible, i.e., below 7 micromolar per liter of blood plasma. Laboratories usually regard levels up to 15 micro mol/L as normal, but epidemiological data reveal that homocysteine levels above 6.3 reflect a steep, progressive increase in the risk of a heart attack. (Robinson et al., 1995) Though the incidence of hypertension, thrombotic stroke, peripheral vascular disease (gangrene), blood vessel toxicity, and the risk of heart attack escalate as homocysteine levels increase, tests to measure homocysteine are not routinely ordered in a cardiovascular workup.

The incrimination of homocysteine in the disease process continues:

	While the focus of this protocol is upon cardiovascular disease, it should be noted that individuals suffering with Alzheimer's disease, depression, eye problems, liver damage, several types of malignancies, i.e., acute lymphoblastic leukemia, breast, pancreatic, and ovarian cancer, Crohn's disease, ulcerative colitis, and irritable bowel disease, often, present with elevated homocysteine levels. (Clarke et al., 1998) (Cattaneo et al., 1998) (Mayer et al., 1997) (Refsum et al., 1991) (Romagnuolo et al., 2001)
	Plasma homocysteine levels predictably increase with elevations in creatinine. Chronic renal failure can cause homocysteine levels to skyrocket up to 4 times normal value. (Wilcken et al., 1979) (Chauveau et al., 1993)
	The link between hyperhomocysteinemia and hypothyroidism is clearly drawn in the sections devoted to Hypothyroidism and Soy Protein appearing in this protocol.
	Patients with pernicious anemia (PA) are frequently hyperhomocysteinemic; elevated homocysteine levels are, in fact, helpful in diagnosing PA. (Savage et al., 1994)
	Homocysteine metabolism is impaired in patients with type II diabetes. Intramuscular injections of 1000 mcg of methylcobalamin daily for 3 weeks reduced elevations of plasma homocysteine in diabetic test subjects. (Araki et al., 1993)

To read about the impact smoking, diabetes, stress, genetics, and hypothyroidism has upon homocysteine levels, please consult the section in this protocol devoted to Traditional Risk Factors. In the Therapetuic Secion, essential fatty acids, magnesium, and homocysteine-lowering nutrients (vitamin B6, vitamin B12, folic acid, and trimethylglycine) detail a program to assist in managing hyperhomocysteinemia. Because of homocysteine's role in sulfur and methyl group metabolism, elevated levels of homocysteine would be expected to negatively impact the biosynthesis of SAMe, carnitine, chondroitin sulfate, coenzymeQ10, creatine, cysteine, dimethylglycine, epinephrine, glucosamine sulfate, glutathione, melatonin, pantethine, phosphatidylcholine, and taurine. Many of these substances are profiled in the Therapeutic Section for their cardio-protection/restorative qualities. Short supply of these nutrients could severely disable cardiac performance.

SYNDROME X (Metabolic Syndrome, i.e., insulin resistance and hyperinsulinemia)

Eclectic physicians have, for the past 20 years, judged hyperinsulinism, or Syndrome X, a powerful indicator of an eventual heart attack. For clarity, let it be understood that a syndrome represents clusters of symptoms; in Syndrome X the symptoms are an inability to fully metabolize carbohydrates, hypertriglyceridemia, reduced HDL, smaller, denser LDL particles, increased blood pressure, visceral adiposity, disrupted coagulation factors, insulin resistance, hyperinsulinemia, and, often, increased levels of uric acid.

For years, high uric acid levels have been associated with cardiovascular disease, but the relationship was poorly understood. Dr. Gerald Reaven unraveled the link when he determined that elevations in uric acid are, often, promulgated by Syndrome X; Syndrome X, in turn, is a forerunner to heart disease. (Fang et al., 2000)

Until hyperinsulinemia is diagnosed and a therapeutic course charted, the arteries are under severe attack and the risk of a blood clot increases. Lesions, i.e., wounds and injuries, damage the arteries; attempts at vascular repair corrode the vasculature with atheromatous material, blockading and closing off vital circulatory routes. The population of sticky platelets increases, as well as the production of free radicals. Lipogenesis (the production and accumulation of fat in arterial tissue) encourages smooth muscles in the vasculature to proliferate. Along with excessive amounts of fibrinogen (a plasma protein that encourages the clotting of blood), PAI-1 (an inhibitor of the fibrinolytic process) becomes more active, further increasing the likelihood of a blood clot. HMG-CoA reductase, the rate-limiting enzyme involved in hepatic cholesterol production, appears simulated in both diabetic and non-diabetic animal studies amidst high levels of insulin. (Dietsschy et al., 1974)

Syndrome X interferes with glucose delivery, a consequence initiated by insulin's nonresponsiveness at the receptor site on the cell. Normally, ordinary levels of insulin will escort glucose into the cell, leaving a bloodstream favoring neither hyper or hypoglycemia. In Syndrome X, the receptor turns a cold shoulder to the hormone and insulin is no longer able to deposit its cargo; as a result glucose loads up in the bloodstream. The pancreas is aware of the problem and attempts to resolve it by discharging more and more insulin. The logic appears to be: since normal levels of insulin cannot get the job done, perhaps greater and greater amounts of circulating insulin will be able to drive glucose, the principal metabolic fuel, into our 60 trillion cells.

In most cases of type 2-diabetes the problem is insulin resistance and inadequate compensatory insulin; in Syndrome X, insulin resistance and excessive amounts of insulin are the hallmarks. The vast difference between the two conditions is that in Syndrome X, the pancreas does not falter in its effort to pump out insulin. It sounds as if the host has won but the following reasons discredit this logic.

For example, hyperinsulinemia increases the risk of hypertension (twofold), hypertriglyceridemia (three to fourfold), type 2-diabetes (five to sixfold), and reduces HDL cholesterol levels. The Quebec Cardiovascular Study found that individuals with elevated levels of triglycerides and LDL cholesterol, plus low HDL cholesterol had 4.4 times the risk of heart disease compared to men with none of the risk factors. But, the risk soars to twenty fold in men with similar cardiovascular profiles who are also hyperinsulinemic. The Quebec study showed that with each 30% elevation in insulin levels, there was a 70% increase in the risk of heart disease over a five-year period. (Despres et al., 1996)

Many physicians fail to consider insulin resistance as a forerunner to both type 2 diabetes and cardiovascular disease. A fasting blood glucose above 115 mg dL, triglycerides above 160 mg/dL, HDL cholesterol (one fourth of total cholesterol), blood pressure persistently over 140/90 mmHg, total cholesterol above 240 mg/dL, and 10-15 pounds of extra weight usually gives a fair indication as to whether or not the patient has some degree of insulin resistance. (Challem et al., 2000) If fasting or two-hour postprandial (after meal) insulin levels are measured, a normal range is 6-35 mcIU/mL; a normal two-hour postprandial glucose is generally between 70-139 mg/dL. (Fasting and two-hour postprandial insulin levels are not standardized; subsequently variances in reference ranges occur.) Even if these tests are run, physicians, often, err in properly assessing the cumulative values of multiple irregularities. The signs are all there, but failure to connect the dots can lead to a treatment that never addresses the source of the ill health.

Syndrome X is, largely, a nutritional disease that is manageable with dietary corrections, i.e., reducing carbohydrates as sweets, pastas, and breads and instating "good fats" in carbohydrates place. (Consult the section entitled Essential Fatty Acids in this protocol for a discussion concerning good and bad fats.)

It has been determined that the quantity of food consumed, as well as the type of food selected, determines how much insulin must be supplied. The Harvard University School of Public Health announced that women between the ages of 38-63 increased their risk of heart attack by 40% if their diet contained quantities of carbohydrates, particularly of refined nature. Though refined carbohydrates are the most maligned, even starchy vegetables, as potatoes, corn, yams, carrots, peas, and most beans can be troublesome to some.

Dr. Gerald Reaven, renowned authority on Syndrome X believes an appropriate breakdown of the food groups should be about 45% of calories from carbohydrate, 40% from fat, and 15% from protein. Substituting fats for carbohydrates quiets an insulin release from the pancreas, and a primary step in Syndrome X has been aborted.

Dr. Reaven cautions that current dietary recommendations, i.e., replacing fats with carbohydrates may be fine for some individuals but a grievous, even fatal, suggestion for those insulin resistant.

To read more about Syndrome X, consult the areas entitled Hypertension, Obesity, Sedentary Lifestyle, Fibrinolytic Activity, and Beta-Blockers. Also, the Therapeutic Section has supplemental recommendations to assist in controlling Syndrome X, including alpha lipoic acid, conjugated linoleic acid, DHEA, essential fatty acids, magnesium, thiamine, vitamin A, and vitamin C.

C-REACTIVE PROTEIN

C-reactive protein (CRP) is a marker for systemic inflammation that raises several hundred-fold in response to acute tissue injury but stays relatively stable in the absence of inflammation. CRP appears in the serum before the erythrocyte sedimentation rate begins to rise, often within 24-48 hours of the onset of inflammation. Elevated CRP levels can indicate the presence of chronic low-grade inflammation, which have been linked to blood vessel damage and vascular disease. High levels of CRP appear to alert inflammatory processes that have the potential to disrupt fatty plaque build-up inside blood vessels, causing a critical rupture; the end result is a blood clot.

When CRP levels are factored in as a cardiovascular risk, along with hypertension, diabetes, elevated cholesterol, family history, and body mass index, there is a significant improvement in predicting cardiac health compared with models that exclude CRP testing. According to Dr. Paul Ridker and Dr. Nader Rifai of Harvard Medical School, ten prospective studies (6 in the U.S. and 4 in Europe) have consistently shown that hs-CRP is a powerful predictor of future first coronary event in apparently healthy men and women. (hs refers to high sensitivity testing, the only method able to discriminate the subtle differences in CRP concentrations in healthy subjects with low normal values.)

Circulation reports that CRP appears able to bind with LDL cholesterol (a union that increases stickiness and increases vascular adherence). (Zwaka et al., 2001) CRP accomplishes this by preparing LDL cholesterol for uptake by macrophages and increasing the formation of foam cells. Macrophages, gorged with fats contained in blood, become bloated and develop into foam cells. When they have reached their maximum load, they explode, discharging their fatty contents into the blood vessel wall at the site of injury. The presence of added fat signals the need for more macrophages to clean up the mess. They stuff themselves, explode, and the cycle starts anew. By causing LDL cholesterol to oxidize into a more reactive, abrasive form, CRP becomes an initiator in this vicious cycle. (Braley, 1985)

New as CRP is to many as a risk factor in coronary artery disease, Rudolf Virchow, a German pathologist living from 1821-1902, hypothesized that inflammation was the causative factor in the atherogenic process. Decades later, scientists confirmed that increased monocytes (white blood cells critical in early plaque development) and macrophages (mononuclear phagocytic cells capable of scavenging and ingesting dead tissue and degenerated cells) are present, particularly at points of plaque rupture. CRP and several other inflammatory markers may be elevated many years prior to a coronary event.

Data from the University of Texas Health Sciences Center indicate that CRP is, however, more than a measurable antecedent, preceding a cardiac problem. CRP along with the cooperative efforts of an unidentified serum factor, acts directly upon the blood vessels, activating adhesion molecules in endothelial cells, i.e., intercellular adhesion molecule (ICAM-1) and the vascular cell adhesion molecule (VCAM-1).

In the Physicians Health Study, middle-aged men deemed healthy at baseline were evaluated over an 8-year period in regard to CRP levels and a cardiovascular event. Those with levels of CRP in the highest quartile at baseline had a twofold increase in the risk of future stroke, a threefold increase in the risk of a myocardial infarction and a fourfold increased risk of undergoing surgery for peripheral vascular disease, compared with the study participants with lower levers of CRP. One of hs-CRP's strengths is its ability to detect at-risk patients with normal cholesterol levels. (Rifai et al., 2001)

Researchers hypothesized in the Journal of the American College of
Cardiology that the cytomegalovirus (CMV) (herpes-type viruses) may stimulate an inflammatory response, reflected by elevated CRP levels. (Zhu et al., 1999) The Journal Circulation reported that older people who had the herpes simplex I virus had twice the risk of having a heart attack or dying from heart disease as those never infected by the virus. (Siscovick et al., 2000) Since the relationship between CMV and coronary heart disease is not observed in all people, researchers consider the ability of individuals to control CMV inflammatory activities the variable in the progression to a myocardial infarction. Note: The infectious process in heart disease is chronicled in numerous studies, but the mechanisms are poorly understood. For example, some researchers completely absolve viruses, i.e., the cytomegalovirus, herpes, and hepatitis B and C from the infectious process that terminates in arterial disease, believing only bacterial infections are precursors to heart disease. (Stefan et al., 2001)

Figure 4 shows the risk factors associated with CRP, extracted from publications authored by Dr. Paul Ridker. It is important to note that risk factors vary according to individual publications and may change with future publications.

Current research indicates that persistent CRP elevation, i.e., lasting longer than 96 hours, after successful coronary stent implantation, is predictive of prolonged inflammation leading to restenosis. Patients who developed restenosis within the first 6 months had increases in CRP levels for up to 96 hours following the procedure, although their baseline CRP had been normal. Patients without restenosis displayed an increased CRP level that was sustained for no longer than 48 hours and subsequently decreased. Higher CRP levels appear predictive of less satisfactory end results, following angioplasty and stent procedures.

Similar predictive values apply to stroke patients. Patients with the highest CRP levels had nearly 2.4 times greater risk of a vascular event or death within the next year compared to stroke patients with the lowest levels.

The risk of stroke, according to data reported in the New England Journal of Medicine, decreased among those using statin drugs to 3.7% compared to 4.5% in the placebo group. (White et al., 2000) The Cholesterol and Recurrent Events trial concluded that pravastatin (administered long-term) appears to be doing more than reduce cholesterol, perhaps acting as an anti-inflammatory. The NEJM reported that Pravastatin reduced C-reactive protein levels after both 12 and 24 weeks administration, independent of LDL cholesterol. It appears statin therapy may prevent coronary events among individuals with relatively low lipid levels but with elevated levels of CRP. (Ridker et al., 2001) Conversely, some drugs including hormone replacement therapy, actually increase CRP levels and the inflammatory response. JAMA reported that large LDL cholesterol, an independent predictor of coronary events in a typical population with myocardial infarction, was not present among patients who were treated with pravastatin. (Campos, 2001)

Though many of the newer risk factors are not yet standardized, some labs are using a CRP reference range of 0.24-1.69 mg/L. (Recent medical events resulting in tissue injury, infections, or inflammation, may increase CRP levels, and if not factored into clinical interpretations can distort results.)

To read more about factors affecting C-reactive protein levels, consult the areas referring to Smoking, Obesity, Sedentary Lifestyle, Gender, Gum Disease, and Link Between Infections and Inflammation in Heart Disease. (Improved glycemic control and normalizing blood pressure may also assist in reducing inflammation and lower CRP levels.)

CRP appears responsive to aspirin, DHEA, fish oil, Pravastatin, vitamin C, vitamin E, and vitamin K supplementation. (Consult the Therapeutic Section to learn more about the natural products.) As research continues, it may be found that many other nutrients and herbals known for their anti-inflammatory properties are equally valuable in maintaining healthy CRP levels. Note: CRP appears to cause depletion of vitamins A, C, and E, as well as carotenoids, zinc, and selenium. Individuals with elevations in CRP may wish to emphasize these nutrients for their contribution to cardiac health.

LINK BETWEEN INFECTIONS AND INFLAMMATION IN HEART DISEASE

Infections are of interest because of the increasing attention paid to the role of inflammation in heart disease, according to David S. Siscovick, M.D., professor of medicine and epidemiology at the University of Washington. Data incriminates the infectious process in various phases known to contribute to heart disease. For example, current research suggests that infection may be an important determinant of fibrinogen levels, offering one possible explanation for the association between chronic or acute infection and vascular events. (Khaw et al., 1997)

During the flu season, the rate of death from ischemic heart disease markedly increases, particularly among the elderly. One reason for this appears to be that patients with influenza A, a flu virus, tend to have much higher levels of CRP (a marker for acute inflammation triggered by infection).

Angina pectoris appears less a prognosticator of a forthcoming heart attack than a febrile (flu-like, feverish) infection prior to the attack. Peter Ammann, M.D., of the Department of Cardiology, Triemli Hospital in Zurich, states that he has observed significantly higher numbers of myocardial infarctions among patients with febrile conditions, mainly of the upper airways, within 2 weeks prior to infarction. Research is divided in regard to which types of infection potentiate a heart attack. Some researchers believe that both viral and bacterial infections are associated with an increase in CRP levels, meaning either one can play a role in initiating a heart attack; others incriminate only bacteria.

Bacteria appear to gain entry into the heart via immune cells, most likely activated in the process of clearing infections from the respiratory passages. The bacteria most suspected of initiating coronary problems are C. pneumoniae, P. aerogenes, E. endocarditis, S. aureus, E. faecalis, C. albicans, and V. streptococcus. (Some researchers add H. pylori, a bacteria associated with duodenal ulcers, peptic ulcers, and chronic gastritis to the list.)

A higher white blood cell count, common when the body is fighting off infection, is associated with an increased coronary risk by diminishing blood flow to the heart muscle and encouraging blood clot formation. The higher the white blood cell count, the higher a patient's risk of death from a heart attack or of developing congestive heart failure.

Tissue specimens, from patients who had undergone a carotid endarterectomy, showed high levels of C. pneumoniae in 11 out of 17 cases. The American Heart Association, also, reported that C. pneumoniae was found in the infected arteries of autopsied cardiac patients. (Vink et al., 2001) Dr. Tatu Juvonen, from Oulu University Hospital in Finland, explains that C. pneumoniae is a specific microbial antigen that causes inflammation and atherosclerotic cells to proliferate.
An alternative to this dismal situation may be antibiotic therapy, controlling the inflammatory process attacking the vessel wall. British researchers propose that administering antibiotics to patients after a myocardial infarction could reduce future complications and cardiac deaths by as much as 15%.

Inflammation appears an independent risk factor that may explain cardiovascular disease in the presence of normal cholesterol, blood pressure, and coronary arteries. MINC patients, i.e., individuals experiencing a myocardial infarction with normal coronary arteries, should be at lower risk for a cardiac event, since they, most often, have normal electrocardiograms, higher HDL levels, and no significant impairment in LDL cholesterol. Dr. Ammann believes the trigger may be systemic inflammation or specific infective agents, advancing a benign complaint to a life-threatening condition. Interestingly, migraine headaches have, also, been observed as forerunners to a heart attack, in otherwise healthy individuals. Turn to section (in this protocol) relating to aortic stenosis to read about inflammation's role in valvular disease.

IS ATRIAL FIBRILLATION PREDICTIVE OF CARDIAC MORTALITY?

Atrial fibrillation, a condition shared by over 2 million Americans, occurs when the atria, the upper chambers of the heart, beats faster than the lower two chambers, the ventricles. Many problems can cause atrial fibrillation, including a leaky heart valve, hypertension, obesity, stimulants (as caffeine and alcohol), medications (as sumatriptan, a headache drug) and thyroid disorders. Dr. Robert Atkins, M.D., adds that patients should be evaluated for heavy metal intoxication and mycoplasmal infections, factors also capable of provoking atrial fibrillation.

It appears that atrial fibrillation is not predictive of cardiac mortality; atrial fibrillation does, however, increase the risk of developing blood clots. Cardiac morbidity occurs in 4% to 6.3% of patients with uncomplicated atrial fibrillation and a stroke in 0.8% to 1.2%. Dr. H.J.G.M. Crijns, of University Hospital Gröningen (Netherlands) declares that even patients with heart failure are not in greater danger because of atrial fibrillation if the condition is well managed.

Blood thinners are, often, prescribed for atrial fibrillation, but a program based in natural medicine is, also, helpful. While full correction of the chaotic rhythm associated with atrial fib is, often, difficult to achieve, nutritional supplements can lessen the risk of a blood clot. Dr. William Campbell Douglass, M.D., states that vitamin E (800 IU daily), cod liver oil capsules (four daily), olive oil (one tablespoon daily), and bromelain (about 750 mg three times per day on an empty stomach) have similar action to Coumadin and aspirin, i.e., thinning the blood and reducing the risk of a thrombotic event. Other "heart nutrients" as, CoQ10, hawthorn, carnitine, taurine, magnesium, and ginkgo biloba are, also, important. Information on each of these supplements appears in the therapeutic section of this protocol.

CONGESTIVE HEART FAILURE

Congestive heart failure (CHF) reflects the heart's inability to pump sufficient amounts of oxygenated blood to supply the body's needs. It does not mean the heart has ceased to work, but rather that the heart's pumping mechanism is performing inadequately. Conditions that damage the heart, as a heart attack, ischemic heart disease (a lack of oxygen in tissue cells), cardiomyopathy (fibrous tissue partially replaces heart muscle and blood no longer moves efficiently), alcohol abuse, congenital and rheumatic fever, arrhythmias, pericarditis (inflammation of the thin sac covering the heart), or drug toxicity can result in CHF. Symptoms of CHF are fluid retention, fatigue, weakness, and unjustified dyspnea, i.e., shortness of breath after slight exertion. In some cases, liver and kidney function is, also, disrupted.

CHF occurs when the heart fails to adequately pump blood through the largest organ of the human body, i.e., 65,000 miles of blood vessels (the vascular system). This breakdown causes increased pressure in the circulatory system, allowing fluid to escape from the bloodstream and accumulate in tissues and organs. More than a hundred years ago, CHF would have been diagnosed as dropsy, i.e., an abnormal accumulation of clear, watery fluid in a body tissue or cavity. Dropsy was the most common of all forms of heart problems until the current epidemic of coronary diseases.

The heart is a two-sided instrument, having a right and left atrium and a right and left ventricle. The atria of the heart receive blood from veins and function as reservoirs before the blood enters the ventricles. The ventricles are the major pumping chambers of the heart, ejecting blood into the arteries and forcing it throughout the vascular system.

Just as there are two sides to the heart, there are two types of heart failure (right sided and left sided). The right side of the heart has the job of moving the blood through the pulmonary blood supply to the lungs, where it picks up oxygen. If the failure occurs on the right side of the heart, it means the right side is not keeping pace with the left side and blood accumulates in the vessels leading to the heart. Excess fluid as peripheral edema occurs in the lower legs, ankles, and feet. (Atkins, 1988)

In left-sided failure, the ventricle that normally pumps blood from the lungs through the aorta to the entire body lags in its effort compared to the right side. Blood accumulates in the veins leading from the lungs and the lungs become congested. Terms as pulmonary edema or fluid in the lungs, usually, mean the left side of the heart is failing, allowing the congestion. The patient may experience shortness of breath (most evidenced upon exertion) or paroxysmal nocturnal dyspnea (shortness of breath occurring after several hours of sleep). Acute pulmonary edema can be fatal. Often, left-sided and right-sided failures coexist, meaning the patient may suffer from both at the same time.

Traditional medicine treats CHF with diuretics and inotropic drugs, i.e., drugs that increase the contractility of the heart. If overweight, a weight loss program will probably be recommended, as well as an individualized exercise regime. Abstinence from tobacco, either direct or second hand, is essential. Experimental studies have shown that administration of nonsteroidal anti-inflammatory drugs (NSAIDs) to susceptible individuals can lead to the development of congestive heart failure. Researchers conclude that there have been few epidemiological investigations equal to the importance of this finding. (Page et al., 2000)

Dispersed throughout the therapeutic section of this material are numerous supplemental suggestions to benefit the patient with CHF. (Read about alpha-lipoic acid, L-arginine, L-carnitine, coenzyme Q10, hawthorn, vitamin B6, selenium, taurine, and thiamine.) Diet, also, plays an important role. For example, carbohydrate restriction exerts a diuretic effect, prompting an immediate loss of salt and water. Ridding water accumulations from saturated tissue is of great advantage to individuals with high blood pressure and congestive heart failure.

VALVULAR DISEASE
Material collected, in part, from ACC/AHA guidelines for the management of patients with valvular heart disease

The purpose of heart valves is very uncomplicated. Valves simply route the blood in the forward direction, preventing its backward flow. Functioning properly, valves are control devices, opening and closing with each beat of the heart, warranting a healthy lap around the circulatory system. But, valves can be damaged by rheumatic fever, infections, injuries, tumors, and calcification, hampering their ability to direct the blood supply.

Some valves, once injured, pose more serious health hazards than others; those include the mitral, aortic, and the tricuspid valves and are the focus of this section of the material.

MITRAL VALVE
The mitral valve, or bicuspid valve, is located between the left atrium and the left ventricle. (The mitral valve is the only valve with two rather than three cusps.) The mitral valve allows oxygenated blood to flow from the left atrium into the left ventricle, but prevents blood from flowing back into the atrium. As blood is forced against the valve, it closes the two cusps, allowing a smooth trajectory from the ventricle to the aorta.

MITRAL VALVE PROLAPSE
Mitral valve prolapse (MVP) or floppy valve syndrome is a slight deformity in the valve separating the left atrium from the left ventricle, a condition that affects 5% to 10% of the population. During MVP, one or both of the cusps, protrude back into the left atrium, causing the floppy valve appearance.

Mitral valve prolapse is fairly benign in most patients, but about 1% to 10% of MVP patients have serious problems, i.e., chest pain, arrhythmias, and leakage of the valve, leading to congestive heart disease. Coenzyme Q10 and magnesium (detailed in the Therapeutic Section of this protocol) are of significant advantage to individuals with MVP.

MITRAL VALVE REGURGITATION
Mitral regurgitation, i.e., the backflow of blood from the left ventricle back into the left atrium, occurs because the valve is too leaky. The mitral valve can become regurgitant for many reasons, including the aging process, rheumatic valvular disease, endocarditis (inflammation of the heart's inner lining and heart valves), chest trauma, or a previous heart attack. Mild but chronic regurgitation does little to alter the overall cardiac health of the patient, but if the condition is moderate to severe, the left ventricle and left atrium can enlarge because of the increased volume of blood. Enlargement of the left atrium can cause symptoms of fatigue, pulmonary edema, atrial fibrillation, and atrial thrombi.

Enlargement of the left ventricle can cause congestive heart failure.
The leakage can be repaired by either surgery and/or insertion of a metal ring around the valve to assist in holding the valve in shape. If surgical replacement is elected, the diseased valve is cut out and replaced with a prosthetic heart valve.

Knowing when to perform the surgery is critical. The consequences of waiting too long may negate any surgical advantage because of enlargement and damage to the left ventricle. Leakiness (regurgitation) occurring in a damaged valve can actually make the job of the left ventricle easier. The effort expended by the left ventricle when the valve is leaking is less than when the valve is repaired. The weakened left ventricle may not be strong enough to keep pace with the efficiency of the repaired or artificial valve. Therefore, the first sign of left ventricular impairment may be the best clue that it is time to consider surgery.

MITRAL VALVE STENOSIS
Mitral stenosis occurs when the mitral valve is too tight, and the blood cannot flow easily from the left atrium to the left ventricle. To compensate, the left atrium will enlarge to develop the extra pressure to push the blood into the ventricle. As pressure in the left atrium increases, blood pools in pulmonary vessels. The excess blood then seeps out into the air spaces of the lungs, and shortness of breath results.

If the condition is mild, there is a minimal effect on the overall health of the person. Some patients, however, experience significant symptoms as fatigue, dyspnea (shortness of breath), orthopnea (requires sitting or standing to breath comfortably), and cyanosis (a bluish discoloration of the skin and mucous membrane. Mitral valve stenosis can lead to atrial fibrillation, which if not well managed, increases the risk of stroke. Atrial fibrillation/mitral valve stenosis patients have about a 5% per year increased risk of having a stroke.

Therapeutic choices include balloon valvuloplasty (a procedure in which one or more balloons are placed across a narrowed valve and inflated to decrease the severity of stenosis), mitral commissurotomy (a procedure to increase the size of the opening by separating adherent, thickened leaflets), or replacement with a prosthetic valve. The two methods of repair are not permanent; the valve will become stenotic in about 5 to 15 years. A mechanical prosthetic valve requires chronic anticoagulation therapy. Dispersed throughout the therapeutic section are supplemental suggestions to preserve the integrity of the mitral valve.

TRICUSPID VALVE
The tricuspid valve has three main cusps and is situated between the right atrium from the right ventricle. The right atrium receives blood returning from the body and pushes the blood into the right ventricle. As the right and left ventricles relax during the diastolic phase of the heartbeat, the tricuspid valve opens, allowing blood to enter the ventricle. During the systolic phase of the heartbeat, both blood-filled ventricles contract, pumping out their contents, while the tricuspid and mitral valves close to prevent any backflow.

TRICUSPID REGURGITATION
Tricuspid regurgitation is a condition in which the tricuspid valve becomes leaky, allowing blood to flow backward from the right ventricle into the right atrium. It can occur by itself or in combination with a disease process that elevates right ventricular pressure.

When tricuspid regurgitation occurs by itself, perhaps due to subacute bacterial endocarditis (a bacterial infection of the valves of the heart), regurgitation does not pose much of a problem. But, when tricuspid regurgitation occurs in union with mitral stenosis or lung disease, fatigue, abdominal discomfort, nausea, and swelling of the legs and feet result. If surgery is scheduled to correct another cardiac problem, the tricuspid valve should be evaluated for surgical repair at that time. Otherwise, medical treatment includes a low-salt diet, diuretics, and digoxin (digitalis).

TRICUSPID STENOSIS
Tricuspid stenosis is a condition in which the tricuspid valve is too tight. Symptoms of tricuspid stenosis, closely, parallel those of tricuspid regurgitation, i.e., nausea, fatigue, abdominal discomfort and swelling of the legs and feet. Patients are, frequently, advised to follow a low sodium diet and to use diuretics; if atrial fibrillation develops, digitalis may be prescribed. Balloon valvuloplasty or valve replacement is, usually, recommended if medical treatment proves ineffective. Because the risk of thrombus is higher in the tricuspid position than in the mitral, bioprosthetic valves appear better than mechanical, despite their limitations.

AORTIC VALVE
The aortic valve, composed of 3 semilunar cusps, is located between the left ventricle and the aorta. The aortic valve prevents blood from flowing back into the left ventricle from the aorta.

AORTIC STENOSIS
Aortic stenosis is a condition in which the aortic valve is too tight. This means that the opening through which blood must flow is too small; consequently, the left ventricle must generate higher pressure to maintain normal blood flow. It usually takes decades for the condition to fully develop. Not until the aortic valve area has narrowed to one-fourth its normal size do circulatory problems become significant.

The most common cause of aortic stenosis in adults is a degenerative-calcification process that immobilizes the aortic valve cusps. The calcific process can either decrease worthiness of the valve or result in total fusion. Studies implicate a chronic inflammatory process in calcium buildup, leading to aortic valvular stenosis. Therefore, long-term anti-inflammatory therapy may be beneficial. Consult the Therapeutic Section of this protocol for information relating to vitamin K and its effort to keep calcium in the bones and not in vessels.

The degree of closure does not always correlate to symptoms. Thus, aortic valve replacement is usually reserved for patients experiencing symptoms rather than those with narrowing but asymptomatic (without symptoms). Eventually, angina, syncope (fainting), and heart failure may develop. After the onset of symptoms, average survival is less than 2 to 3 years.

Fifty-one asymptomatic patients with severe aortic stenosis were followed for an average of 17 months. During this period, 2 patients died, with cardiac symptoms preceding the deaths. Other studies have shown similar survival trends among asymptomatic patients. (Sudden death occasionally occurs in the absence of symptoms, but the numbers are small, i.e., <1% per year.)

Once symptoms have become apparent, surgery becomes the patient's best option. In theory, the aortic valve can be replaced in almost all patients, even octogenarians, who are otherwise in good health. Although insertion of a prosthetic aortic valve is associated with low perioperative morbidity and mortality, complications arise at the rate of at least 2% to 3% per year, and death due directly to the prosthesis at about 1% per year. If the patient is symptomatic but inoperable-digitalis, diuretics, and angiotensin converting enzyme (ACE) inhibitors are, usually, prescribed.

AORTIC REGURGITATION
Aortic regurgitation occurs when the blood flows from the aorta back into the left ventricle. Some of the blood that should be flowing to the body from the heart flows back into the left ventricle. As a result, the left ventricle has to pump harder to move the blood though the circulatory route and back to the heart. A few of the factors provoking aortic regurgitation include congenital deformities, calcification, rheumatic fever, infective endocarditis, systemic hypertension, and anorexic drugs (those that diminish appetite).

Acute aortic regurgitation is a medical emergency. During acute, severe aortic regurgitation, the left ventricle does not have time to make the necessary adjustments to accommodate the backflow and, as a result, forward stroke volume decreases. Tachycardia (heartbeat over 100 beats per minute) occurs as a compensatory mechanism, but the effort is, usually, not equal to the task. Pulmonary edema and/or cardiogenic shock, a condition of critically low cardiac output can result. (About 80% of events involving cardiogenic shock are fatal.)

Conversely, in chronic aortic regurgitation, a number of compensatory adjustments occur, rendering aortic regurgitation less dangerous. In fact, the majority of patients remain asymptomatic through this compensated phase, which may last for decades. With time, the left ventricle progressively enlarges, and depressed myocardial contractility increases. This can progress to the extent that the full benefit of surgical correction, i.e., recovery of left ventricular function and improved survival, are no longer possible.

The results of 7 studies, involving 490 asymptomatic patients with chronic aortic regurgitation, who were followed for an average of 6.4 years, gives a brief history regarding the developmental patterns of the condition.

	The rate of progression to symptoms and/or left ventricle dysfunction averaged 4.3% per year. (As the left ventricle goes, so goes the heart.)
	Sudden death occurred in 6 of the 490 patients (an average mortality rate of <0.2% per year).

ARE ARTIFICIAL VALVES AS GOOD AS NATURAL VALVES?

The replacement of diseased natural heart valves with an artificial valve can be life saving, but the replacement valves are never considered as good as healthy natural ones. There are two general types of valves: mechanical and bioprosthetic (usually taken from pigs). The mechanical valves last longer but require the patient to take anticoagulants. The bioprosthetic valves do not require long-term anticoagulation therapy, but they, frequently, must be replaced after about 10 years in adults. Their replacement comes quicker in children and those on kidney dialysis.

The major risk of prosthetic heart valves is stroke. Those taking anticoagulants reduce the incidence of stroke, but the risk is not totally eliminated.

The following natural products are of value to patients with valvular disease. To learn more about these supplements, please consult the therapeutic section.

VASODILATORS: Garlic, Ginkgo biloba, Magnesium, and Niacin
ACE INHIBITORS: Green tea, Garlic, Hawthorn, Olive leaf, Taurine, Proanthocyanidins (mild ACE inhibitor), Angelica, and Ginkgo biloba
CALCIUM CHANNEL BLOCKING ACTIVITY: Magnesium, Angelica, Green Tea, and Proanthocyanidins
DIGITALIS LIKE ACTIVITY: Bugleweed, Taurine, and Cactus
DIRURETICS: Bugleweed, Hawthorn, Vitamin B6, Taurine, Angelica, Vitamin C, Vitamin E, and Angelica.
ANTI-INFLAMMATORIES: Aspirin, Bromelain, Chondroitin, Curcumin, DHEA, EFA's, Ginger, Vitamin C, Green Tea, Angelica, Ginkgo biloba, and Cactus

THERAPEUTIC SECTION

Note to herbal users: Herbal medicine is a significant force on the health scene. Guaranteed potency of major active constituents, a process referred to as standardization, has notably advanced the industry's acceptability. When buying a standardized herbal, the consumer knows exactly how much of the active ingredient they are getting. Guess work is eliminated.

Does this mean that standardized herbs are the only herbs to buy? Those who advocate whole-herb preparations argue that there are many, many compounds in any given herb and that these compounds act synergistically to provide maximum benefit to the user. (White, 2000) For example, St. John's Wort is standardized to contain a given amount of hypericin, the compound thought responsible for the herb's ability to dispel depression. Newer research suggests, however, that another compound in St John's Wort (hyperforin) may also be delivering therapeutic advantage, and, as research continues, the list may grow.

Those who favor standardization assert that without an arduous process of concentrating and measuring, the therapeutic value of any herb remains uncertain. So which voice best serves the consumer? In truth, both contentions are valid. For this reason, many companies emphasize the active constituent (if known) but complex the herb with the full plant, i.e., all naturally occurring agents.

Because mainstream medicine has (until recently) largely considered herbals irresponsible medicine, the industries scientific awakening has come slowly. Thus many of the active agents, i.e., those responsible for therapeutic gain have not been identified. The Therapeutic Section (following) notes the active agents in all herbs currently standardized and profiled in the material. If an herb is not standardized, data extracted from historical archives will be presented. To rebuff a herb because its active ingredient has not been identified denies many (of this generation) optimal use of herbal products. It is imperative, however, that the consumer purchase products from suppliers assuring purity and warranting potencies commiserate with label disclosures.

INTERVENTIONS TO PREVENT AND TREAT CARDIOVASCULAR DISEASE
The following therapeutics are arranged alphabetically, not by order of importance, to render the material more accessible to the reader.

ALPHA LIPOIC ACID (also known as thiotic acid)
Beneficial in preventing and treating Syndrome X, has antioxidant and antidiabetic activity, protects LDL against oxidation, lowers total cholesterol, beneficial in congestive heart failure and strokes, inhibits protein glycation, stabilizes arrhythmias

Some researchers credit alpha lipoic acid with being the principal supplement for preventing and reversing Syndrome X. Lipoic acid earned this reputation by increasing the burning of glucose, a sugar that is converted to energy and used by every cell of the body. The mitochondria (the powerhouse of the cell) are one of the benefactors of enhanced glucose utilization, via the Kreb's Cycle, a process that utilizes glucose, amino acids, and fatty acids to yield high energy. Many of the B vitamins assist in maximizing production from the Kreb's cycle, but perhaps none are as efficient as lipoic acid. Note: Free radicals are produced as a by-product of the energy generated during the Krebs cycle. Alpha lipoic acid appears to quench abhorrent free radicals that are not contained during the reactions.

As glucose is provided to fuel the Kreb's Cycle, blood glucose and insulin levels decrease and, simultaneously, another perk occurs, insulin sensitivity increases. Lipoic acid resulted in a 50% increase in insulin-stimulated glucose disposal and a 27% improvement in insulin sensitivity, compared to a non-supplemented comparable group of diabetic patients. Blood glucose levels, typically, drop by 23-45% in diabetic test animals.

Lipoic acid is of value in treating diabetic and non-diabetic subjects with congestive heart failure. The Mayo Clinic added to alpha lipoic acid's credits, citing its ability to stabilize erratic heart beats in diabetic patients.

Stroke deaths dropped from 78% to 26% in lipoic acid/animal studies conducted by Lester Packer. The journal Stroke confirmed that alpha-lipoic acid reduced stroke infarct volume, inhibited platelet/leukocyte activation and adhesion, while increasing cerebral blood flow. (Clark et al., 2001)

Lipoic acid reduces free radicals and advanced glycosylated end products (AGEs). Glycation occurs when proteins react with sugar to form an AGEs. This process increases the risk of cardiovascular disease by oxidizing LDL cholesterol and rendering blood vessels tough and inflexible. This gradually affects the left ventricle, reducing its ability to pump oxygen-rich blood into the circulation. Stiffness occurring in the myocardium increases diastolic pressure and arterial rigidity increases systolic pressure. Also, glycosylated cholesterol-carrying proteins are no longer capable of binding to receptors on liver cells to signal the cessation of cholesterol manufacture. A healthy cholesterol-carrying protein halts the copious supply of cholesterol. Without this binding process, cholesterol continues to be pumped out. Lipoic acid interrupts all of these processes at the "starting point," by inhibiting glycation.

Alpha lipoic acid is regarded as the "universal antioxidant" because it enhances the activity of other antioxidants. It acts like a "big brother" in regard to vitamin E, coenzyme Q10, and vitamin C, assisting in recycling these important antioxidants for continued service. Lipoic acid's antioxidant qualities appear greater than vitamin E's, because vitamin E works only in the fatty parts of cells, whereas lipoic acid works in both watery and fatty portions.

Antioxidants are extremely important in cardiac health, for the heart is one of the most susceptible of all organs to free-radical damage. (There are three times more free radicals produced in aging hearts compared to young hearts.) Though a normal by-product of oxidative metabolism, free radicals, in excess, are considered germane to the outset of vascular disease.

Most all of nature is two-pronged, i.e., having a good side as well as a bad. According to reports published in numerous medical journals, free radicals participate in many positive reactions, as mitochondrial respiration, prostaglandin synthesis, platelet activation, and phagocytosis, i.e., the engulfing and destruction of microorganisms and cellular debris. The International Journal of Integrative Medicine reminds us that when out of control, these highly unstable electrons can cause extensive damage to lipid membranes, organelle (structures housed within the cell body) and DNA itself. (Sinatra, 2001) It is extremely important to maintain enough nutrient cofactors to support endogenous antioxidant enzyme systems, as glutathione, superoxide dismutase, and catalase and enough supplemental antioxidants to compensate for natural systems that may be lagging. Once again, the key is balance, i.e., to provide enough antioxidants to neutralize excessive oxidants but to retain enough free radical oxidative activity to carry on essential life processes.

The Journal Hypertension reported alpha lipoic acid, a thiol compound known to increase tissue cysteine and glutathione, reduced blood pressure, blood glucose, and insulin levels in spontaneously hypertensive rats. (Vasdev et al., 2000)

Suggested alpha lipoic acid dosage: some researchers believe 50 to 250 mg/day (in concert with other antioxidants) may be sufficient to protect against Syndrome X. Most Life Extension members have been taking between 250 mg and 500 mg a day of alpha lipoic acid. If the patient has unstable blood glucose levels, higher doses of lipoic acid will be required. German practitioners frequently use 600 mg daily as adjunctive therapy in coronary artery disease and 600 to 1800 mg of alpha lipoic acid to improve insulin sensitivity and diabetic conditions. Higher doses should be administered with the help of a qualified physician, who can adjust insulin requirements, as indicated. Note: Dr. Lester Packer, in his book The Antioxidant Miracle, recommends taking biotin supplements with alpha-lipoic acid when the daily intake exceeds 100 mg. Alpha lipoic acid may compete with biotin and interfere with biotin's activities in the body.

READERS GUIDE TO LIPOIC ACID FOOD SOURCES: liver and yeast, spinach, broccoli, potatoes, and red meat.

ANGELICA (Angelica archangelica)
An anti-anginal, antiinflammatory, calcium antagonist, ACE inhibitor, diuretic

Angelica, a member of the carrot family, contains 15 compounds considered calcium channel blockers. One of the calcium blocking compounds in angelica is, in fact, more potent than verapamil (Calan, Isoptin), a popular calcium channel blocker prescribed for angina, atrial fibrillation, and spasms occurring in the blood vessels.

Dr. James Duke, Ph.D., (botanist) comments that it is well known that vegetarians have a low incidence of heart disease. Usually their low-fat diet gets the credit, but Dr. Duke speculates that it may be because they eat lots of plants from the carrot family as, carrots, celery, fennel, parsley, and parsnips, which (like angelica) contain compounds with calcium channel blocking activity. Calcium channel blockers are (whether from the plant kingdom or a pharmaceutical) powerful anti-anginals.

Angelica bestows its cardiac advantage through various pathways. For example, angelica not only reduces the incidence of angina attacks, but, also, regulates an erratic heartbeat. It has diuretic properties, making it of value in the treatment of congestive heart failure and hypertension. Angelica has other mechanisms it uses to reduce blood pressure, i.e., the inhibition of ACE, the angiotensin-converting enzyme.

Inflammation, one of the newer risk factors for heart disease, is, also, reduced by angelica. (Read about the inflammation/heart disease connection in the sections dedicated to Newer Risk Factors.) Suggested angelica dosage: 15 to 30 drops one to three times a day.

L-ARGININE…AN ESSENTIAL AMINO ACID
Dilates blood vessels, reduces blood pressure, replicates the activity of nitroglycerine, needed to produce nitric oxide

L-arginine, along with a properly planned exercise program, appears to amend the abnormal functioning of blood vessels. Individuals with congestive heart failure, often, have blood vessels that fail to dilate in response to certain drugs, a sign that the inner blood vessel wall, or endothelium, is compromised.

A study reported in the American College of Cardiology concluded that treatment with L-arginine produced a fourfold increase in blood vessel dilation from 2.2% to 8.8%. (Hambrecht et al., 2000) Regular forearm exercises increased the dilation response by the same amount, but the combination of L-arginine and exercise training resulted in an improvement from 2.9% to 12.0%. Doses of 5.6-12.6 gram of arginine increased blood flow to the extremities by 29%; the distance walked on a treadmill in 6 minutes increased by 8%.

Much of L-arginine's effectiveness comes by way of increasing nitric oxide, a blood vessel dilator and clot buster produced in endothelial cells by the enzyme, nitric oxide synthase. Nitric oxide counteracts the vasoconstriction and platelet aggregating effects of the stress hormone adrenaline (epinephrine) and assists in maintaining vascular elasticity. It also increases the activity of the endothelial relaxation factor, needed for expansion and contraction of the arterial system. While L-arginine increases nitric oxide, hypertension, hyperhomocysteinemia, diabetes, and smoking reduce it.

Some cardiologists recommend L-arginine over nitroglycerine, since the two substances appear to replicate similar vascular function, i.e., the ability to relax smooth muscles and dilate blood vessels. Because of arginine's vasodilating properties, it is, frequently, used as a treatment for hypertension. Researchers at the University of Southern California (Los Angeles) speculate that a defect in nitric oxide production may be a possible mechanism of hypertensive disease.

Further bonuses observed during L-arginine supplementation are the amino acid's hypolipidemic effects, even when eating atherogenic foods and its ability to reduce existing vascular plaque. It is thought that arginine shares the latter trait with other T-cell stimulants, as zinc, selenium, vitamins A, and vitamin E. Suggested dosage: 2 grams before bedtime. Arginine caveat: Individuals who have frequent herpes outbreaks may find arginine-rich foodstuffs or supplementation contraindicated. Persons with schizophrenia should avoid doses greater than 30 mg daily.

READERS GUIDE TO ARGININE FOOD SOURCES: Carob, chocolate, dairy products, eggs, meats, oats, peanuts, soybeans, walnuts, wheat and wheat germ.

ARTICHOKE EXTRACT
Reduces cholesterol and triglycerides

Artichoke (Cynara scolymus), a delicious table vegetable, has a reputation that extends beyond culinary enhancement. It has long been used to improve digestive and liver complaints, but, more recently, artichoke has become popular as a hypolipidemic. A study performed at PISGAH Bio-Medical Research Center concluded that concentrated, expressed artichoke flower juice lowered total cholesterol by an average of 35 points and triglycerides by almost 50 points in 12 weeks. Those individuals most needing lipid correction experienced the greatest benefit. Caffeoylquinic acids and flavonoids, powerful components of artichoke, appear to deliver the herbs anti-lipidemic effects.

Artichoke reduces cholesterol by decreasing the synthesis of cholesterol in the liver and increasing the conversion of cholesterol to bile acids. When the liver receives a message that cholesterol levels are too low to supply adequate amounts of bile acids, the liver will comply with copious amounts of cholesterol to compensate for the shortage. Artichoke modulates cholesterol synthesis by signaling that enough cholesterol has been produced to accomplish necessary metabolic tasks.

The flavonoid, luteolin, (contained in artichoke) appears to assist in lowering cholesterol by modulating the activity of HMG-CoA reductase. (Statin drugs reduce cholesterol by competitively inhibiting the binding of HMG-CoA reductase. Tocotrienols degrade the enzyme.) Artichoke research has found no direct inhibition of HMG-CoA reductase, and other enzymatic steps occurring later in the biosynthesis of cholesterol appear unaffected. (Recall that the cholesterol cascade begins with acetyl CoA being converted to HMG-CoA. HMG-CoA reductase reduces HMG-CoA to mevalonic acid. Mevalonic acid participates in several steps that reduce it to squalene. Squalene is then converted to cholesterol.) Regulating the activity of HMG-CoA reductase explains, in part, the cholesterol lowering effects of artichoke.

Suggested dosage: one capsule three times per day, containing 300 mg of artichoke standardized to contain 13-18% caffeoylquinic acid. Note: The American Journal of Clinical Nutrition recently reported that chlorogenic acid, a component of black tea and coffee, could increase homocysteine levels. (Olthof et al., 2001) Chlorogenic acid, also, appears in artichoke and would, therefore, be contraindicated if one had refractory hyperhomocysteinemia.

ASPIRIN…FOR MORE THAN A HEADACHE
Reduces C-reactive protein, platelet aggregation, and cardiac inflammation

Aspirin has been used for over a century to relieve pain; research suggests that it may play an equally important role in heart health. A study, involving 51,085 participants, showed a total of 2284 cardiovascular endpoints occurring during an aspirin trial. The risk of first nonfatal heart attack was reduced by 32% among the aspirin users compared to non-users. The researchers concluded that aspirin therapy could prevent a third of myocardial infarctions in apparently healthy individuals. (Hebert et al., 2000) JAMA reported that aspirin usage, among patients undergoing stress echocardiography, was independently associated with reduced long-term all-cause mortality, particularly among older subjects, with known coronary artery disease and impaired exercise capacity. (Gum et al., 2001)

Three studies looked at the incidence of stroke subtypes among aspirin users. A 1.69-fold increase in the risk of hemorrhagic stroke occurred among aspirin users, but no increase in ischemic strokes was noted. Secondary prevention trials, evaluated by Drs. Patricia R. Hebert (Yale University) and Charles Hennekins (University of Miami), indicated that aspirin therapy administered to 10,000 persons would prevent 67 myocardial infarctions and cause, approximately, 11 hemorrhagic strokes. In November 2001, the New England Journal of Medicine published that over a two-year period, no difference was found between aspirin and warfarin in the prevention of recurrent ischemic stroke or death or in the rate of major hemorrhage. (Mohr et al., 2001)

The drug disposition of aspirin is persuasive, when applied to a cardiovascular model. For example, low-dose aspirin (81 mg) appears to provide partial protection against abnormal blood clot formation, having a 2-day lasting effect on blood platelets. Platelets become less sticky, and the risk of a heart attack and transient ischemic attacks (TIAs) are, subsequently, reduced.

Aspirin exerts some of its cardio-protection by inhibiting the enzyme cyclooxygenase, a trigger in the inflammatory process. One molecule of aspirin will destroy the cyclooxygenase enzyme for 4 to 6 hours. (Read the sections devoted to C-reactive protein and Link Between Infections and Inflammation in Heart Disease to learn how the inflammatory process advances cardiac disease.)

Aspirin appears to lower C-reactive protein (CRP). In the Physician's Health Study, participants were randomly assigned at baseline to receive 323 mg of aspirin on alternate days and were then followed for first-ever myocardial infarction. The greatest risk reduction occurred in individuals with the highest levels of CRP (55%) and smallest for those with the lowest levels of CRP (13%). The results of this study suggest that in addition to aspirin's antagonism toward platelet clumping, it may also attenuate thrombosis through anti-inflammatory mechanisms.
Aspirin, significantly, cut the death rate from cardiac disease among 2,368 non-insulin-dependent diabetic patients with coronary artery disease. (The aspirin benefit was greater among diabetic patients than non-diabetics.) Diabetic patients using aspirin had a 10.9% mortality risk from cardiac diseases while diabetics not using aspirin had a 15.9% risk. (Harpaz et al., 1998)

The aspirin benefit extended to include carotid endarterectomy patients. Individuals using low-dose aspirin (81 mg to 325 mg a day) reduced the risk of myocardial infarction, stroke and death for a 30-day to 3-month interval following surgery. Individuals taking 650-1300 mg were not similarly protected, illustrating that the dose can alter the end response. (Taylor et al., 1999)

Current information indicates that aspirin can, also, reduce the level of heart damage during a heart attack. When taking aspirin because one believes they are experiencing an acute heart attack, the aspirin should be chewed rather than swallowed, and is best taken within 30 minutes of the onset of symptoms.

Randomized clinical trials, generally, favor taking aspirin as a coronary protectant. The American College of Chest Physicians recommend aspirin for all people over 50 who have one cardiac risk factor and no condition that would circumvent the value of the aspirin. The latter caveat includes those individuals who have increased prothrombin time, disturbed gastric mucosa, or hypertension. Acclaimed as low-dose aspirin is, studies have shown that aspirin does not appear comprehensive enough to prevent a heart attack if fibrinogen levels are excessively high.

BROMELAIN
Anti-inflammatory, reduces fibrinogen, lessens risk of blood clots, beneficial in atrial fibrillation, is hypotensive, relieves angina, basic to smokers

Bromelain, derived from pineapple (Ananas comusus), is regarded as a natural anti-inflammatory, acting as a protein-digesting enzyme. Since the revelation that inflammation may be causal to cardiovascular disease, bromelain has attained new stature. Proteolytic enzymes work directly on the inflammation, neutralizing and removing damaged cell tissue. The digesting nature of bromelain suggests that it can, also, reduce atherosclerotic plaque accumulating in arteries.

Bromelain lowers blood pressure, breaks down fibrinogen, and prevents blood cells from clumping (an act that decreases the risk of blood clot formation). These tenets make bromelain particularly valuable to smokers and patients with atrial fibrillation. According to German studies, a dose of 1000 to 1400 mg per day completely relieved angina.

Bromelain, when used as an anti-inflammatory or protein-digesting enzyme, should be taken between meals. Suggested dosages: 750 mg used three times per day.

BUGLEWEED (Lycopus virginicus)
Diuretic, has digitalis mentality

Bugleweed has a reputation that dates to folk medicine. Historically, herbalists used bugleweed to regulate the heart and improve circulation. Bugleweed's repute is enduring, for practitioners still use the herb to stabilize a rapid or irregular heart rhythm, whether the problem is functional or organic.

Bugleweed is beneficial in the treatment of hypertension and congestive heart failure, ridding water from edematous tissues and organs. It has been called a "natural digitalis," milder but with some of the same characteristics as the drug. Bugleweed does not accumulate and is considered non-toxic. Suggested dosage: 30-40 drops in a little water two to four times a day.

CACTUS (Selenicereus grandiflorus)
Lessens attacks of tachycardia, anxiety, and arrhythmias, faintness, dyspnea, murmurs, angina, and endocarditis

Herbalists believe cactus has a special place among heart remedies, rating it as a heart tonic par excellence. Cactus shows its versatility in treating a broad range of cardiac complaints by improving symptoms associated with irritable heart syndrome, i.e., tachycardia, fatigue, faintness, and dyspnea (shortness of breath).

Stressful situations appear, particularly, invitational to irritable heart syndrome. Important emotional indications for the use of Cactus (drawn from homeopathic concepts) are feelings of anxiety and fear. Individuals overcome with negative emotions appear to most profit from its usage.

Cactus excels when the pulse is irregular and the cardiac response feeble. Cactus wields its corrective force by nurturing the entire nervous and muscular structure of the heart. Valvular mummers, anxiety-provoked cardiac derangement, senile heart disease, angina, and endocarditis, i.e., inflammation of the inner layer of the heart or a heart valve, were improved while using Cactus.

The effectiveness of cactus is most evidenced with sustained usage. Use 30 to 40 drops two to four times a day. (Unlike Digitalis, cactus is non-toxic and does not accumulate.)

CALCIUM
A hypotensive mineral, antiarrhythmic, supports healthy bones around gum tissue, reduces iron overload

Inadequate dietary calcium appears to have a correlation with hypertension. Hypertensive individuals may be, unwittingly, contributing to the problem, by consuming about 18% less dietary calcium than normotensives.

Epidemiologic findings suggest that there is a threshold for the protective effect of calcium, below which the risk of hypertension increases at a greater rate. The set point of this threshold may be about 700-800 mg/day but other variants, such as metabolic type and absorption rates may modify this dosage.

Calcium is not a universal resolvent for hypertension. In some cases, no significant hypotensive effect was noted in dosages as high as 2.5 g/day. The explanation for this is that natural medicine is an individualized discipline. There are multiple causes of hypertension; finding the casual factor in one individual does not guarantee therapeutic value in another. Patients wishing to try calcium as a hypotensive should not withdraw blood pressure medication abruptly, but use the drug in combination with calcium over a 3-6 month assessment period. During this interval, watchful monitoring, may allow a gradual reduction in medication.

Minerals, though usually not considered as focal, are, in many ways, more important to survival than vitamins. One can live longer with a vitamin deficiency than with a mineral shortage. A deficiency of calcium, magnesium, or potassium can force the heart into fatal cardiac arrhythmias.

Calcium is of advantage in reducing iron overload. The American Journal of Clinical Nutrition stated that 300 mg of elemental calcium taken with a meal, reduced the amount of iron absorbed from food by 40%. (Hallbert et al., 1998) Amounts larger than 300 mg did not further reduce iron absorption. Since some individuals become tolerant to calcium-induced iron absorption blockage, it is important to have blood tests, periodically, to evaluate sustained effectiveness. Calcium is, also, important in periodontal disease, a factor that may predict heart health, by supporting healthy bone around gums.

Calcium citrate is a good choice considering absorption, but calcium citrate malate acid is about 30% better absorbed than calcium citrate. Calcium bis-glycinate was shown to absorb 180% better than calcium citrate and 21% better than calcium citrate malate. Dosage suggestions: 1.5 gram of elemental calcium/day.

READERS GUIDE TO FOOD SOURCES OF CALCIUM: Milk and dairy foods are frequently under attack, particularly homogenized products. The reasons according to Dr. Allan Spreen, M.D., are numerous. During homogenization an enzyme appearing in milk (xanthine oxidase) is broken down to a smaller size. The enzyme's altered state allows entry into the bloodstream and a reaction to occur on arterial walls. In a protective gesture, cholesterol is laid down at the site of contact. Milk is, also, often challenged as a worthy source of calcium. It's high phosphorous content and a lack of magnesium is thought to impede calcium absorption. Furthermore, evidence incriminates milk in type 1diabetes. Antibodies the body makes to milk are closely related to antibodies that destroy islet cells (insulin producers) in the pancreas in cases of juvenile diabetes.

Salmon (with bones), sardines, clams, and oysters, sesame seeds, blackstrap molasses, prunes, figs, vegetables, as dandelion greens, mustard greens, broccoli, cabbage, kale, turnip greens, collards, asparagus, and watercress are considered (by many) safer, surer sources of calcium.

THE INTERELATIONSHIP OF FACTORS ACTING ON ABSORPTION: The importance of providing a milieu conducive to nutrient utilization cannot be overstated. For example, in an alkaline medium, calcium forms insoluble and non-absorbable calcium phosphate. Hydrochloric acid lowers the pH of the digestive tract, providing a favorable environment for absorption.

Nutrients also play a role, either supporting or opposing absorption of dietary essentials. For example, the amino acid lysine (found in milk, eggs, fish, limas beans, potatoes, soy products, cheese, and yeast) is needed for calcium absorption. Other calcium enhancers include vitamin D (sunshine), vitamin A, vitamin C, smaller doses of magnesium, and exercise.

Too much zinc can reduce calcium absorption, and too much calcium can interfere with zinc utilization. Diets high in protein and sugar alter calcium uptake; coffee, alcoholic beverages and phosphorous-rich soft drinks, also, promote increased calcium excretion. Oxalic acid (found in almonds, beet greens, cashews, chard, cocoa, rhubarb, soybeans, and spinach) retards calcium absorption by binding with calcium in the intestines, producing insoluble, non-absorbable salts. (Oxalic acid is problematic only if the diet is persistently structured around these foodstuffs.) A union of iron and calcium interferes with full utilization of both minerals. A deficiency in vitamin B6 and overstated amounts of magnesium can hinder calcium absorption. Calcium and tetracycline form an insoluble complex that impairs both mineral and drug absorption.

L-CARNITINE
Energizer, hypolipidemic, aids weight loss, improves circulation, increases exercise tolerance, beneficial treatment in angina, diabetes, congestive heart failure, and cardiac arrhythmias

Robert Crayhon, nutritionist, considers carnitine the single most important nutrient in his practice. Carnitine, a coenzyme similar to the family of B vitamins, is essential for the burning and transport of long-chain fatty acids, the fuel for cardiac energy. Up to 70% of energy produced by the muscles comes from the burning of fats. To expect normal functioning of heart muscles, the transport of carnitine into tissues is critical.

Lysine and cofactors yield about 25% of the carnitine the body needs for optimal performance. The remaining 75% can come from the diet, if food selections are made with a slant toward carnitine-rich foodstuffs, i.e., protein foods, especially mutton, lamb and beef. Interestingly, protein foods, those frequently shunned on a "heart healthy diet," raise HDL cholesterol and increase carnitine levels.

Carnitine is, often, effective in reducing the incidence of cardiac arrhythmias and angina attacks. According to data reported in Drugs Exp Clin Res, patients receiving L-carnitine experienced fewer premature ventricular contractions at rest and improved cardiac output. (Cacciatore et al., 1991) But, if oxygen levels decrease, carnitine, also, decreases and the patient may be in jeopardy from two prospectives.

Patients with stable angina, who were evaluated by means of a stress test, were able to exercise longer before abnormalities were detected while on 900 mg of orally administered L-carnitine. Individuals acting as controls in the study and receiving a placebo experienced distress at 6.4 minutes into the test, while those receiving carnitine supplementation extended the period of symptom-free exercise to 8.8 minutes. The results indicate that carnitine may be an effective alternative to anti-anginal medications i.e., beta-blockers, calcium channel antagonists and nitroglycerine, though never discontinue these medications without consulting with your physician.

Carnitine, 40 mg/kg/day, administered to individuals displaying heart trauma, substantially lessened coronary damage and the risk of occlusion. Arterial plugs were less likely to form as carnitine modulated lipids, with less of the objectionable and more of the beneficial fats produced. After 4 months of carnitine therapy, total cholesterol levels reduced by about 20%, triglycerides by 28%, and HDL increased by 12%. Triglycerides and HDL were more responsive to carnitine supplementation if the diet contained no more than 40% of calories from carbohydrates.

Carnitine is of value in treating congestive heart failure (CHF). A group of 60 men and women (ages 48-73) were selected for a carnitine heart study, having failed conventional treatment. Thirty of the patients were given LPC (L-propionylcarnitine (500 mg/3 times daily) for 180 days, along with their drug regime. At 30 days into the trial the patients were evaluated for improvement in exercise tolerance and left ventricular ejection fraction. Both parameters showed significant improvement at the one-month interval, but improvement was even more pronounced at the 90 and 180-day mark. Exercise tolerance improved by 16.4% at 30 days, 22.9% at 90 days, and 25.9% at 180 days; left ventricular ejection fraction progressively increased by 8.4%, 11.6%, and 13.6% throughout the trial. Note: L-carnitine has been approved by the FDA, under the name Carnitor, as a therapy for congestive heart failure.

Glycosylated hemoglobin, HbA1c, (a hemoglobin molecule chemically linked to glucose) is a test used to evaluate glucose levels over the previous 6-8 weeks. The test measures gycosylation of hemoglobin in the red cells over their lifetime of 90-120 days. HbA1c, for a non-diabetic, is normal at 4% to 6%; for a diabetic, the goal is to maintain HbA1c less than 7%. (7%=an average of 150 mg/dL of glucose.) Carnitine assists in stabilizing blood glucose levels, so that peaks and valleys are less troublesome.

Individuals, who are at increased cardiac risk because of obesity, may find value in carnitine supplementation. Carnitine, especially when combined with omega-3 fatty acids and a decrease in carbohydrate consumption, promotes weight loss. If used for obesity, begin with 500 mg and gradually increase dosage to 2 gram/day. If morbidly overweight, larger doses, i.e., up to 4 gram/day may be required. Hypothyroidism, a contributing factor to both obesity and coronary artery disease, frequently, parallels carnitine deficiencies.

Some practitioners report better cardiac management when using L-carnitine fumarate, a less hygroscopic but more bio-available form of the vitamin-like nutrient. Others prefer LPC (L-propionylcarnitine) for the treatment of angina. Acetyl-L carnitine is touted because of its ability to energize, a result of extremely efficient utilization. Because of the energizing effects of acetyl-L carnitine, Robert Crayhon, author of The Carnitine Miracle, suggests it be taken no later than 3 p.m. to preserve a restful night's sleep.

Suggested carnitine dosage: as with most supplements, dosage is subjective. Some individuals notice increased energy with 1 g of carnitine or 500 mg of acetyl-L-carnitine/day. Clinical studies frequently use from 1500 to 3000 mg daily. Because increased energy production begets a greater generation of free radicals, carnitine should always be used with an antioxidant program.

CARNOSINE…NEWER BOOST TO CARDIOVASCULAR HEALTH
Antioxidant, protects against strokes, and reduces AGEs

In January 2001, the Life Extension Foundation hailed carnosine as a substance capable of slowing many of the processes involved in aging, including cardiovascular degeneration. Carnosine, a combination of the amino acids alanine and histidine, accomplishes this, in part, by playing a duel role in regard to proteins, i.e., yielding a protective effect through antioxidant activity and, also, participating in the repair or removal of damaged proteins. For example, carnosine quenches the destructive potential of the deadly hydroxyl radical and impacts protein degradation that occurs as a result of collagen cross-linking and the formation of advanced glycosylated end products (AGEs).

Glycation is a reaction that occurs when proteins react with glucose. A series of reactions follow (including the oxidation process), terminating in the formation of an advanced glycosylated end product (AGEs), a protein the body cannot break down. These processes decrease vascular tone and resiliency and are factors that influence the progression of cardiovascular disease and hypertension. Glycated proteins produce 50-fold more free radicals than non-glycated proteins; carnosine may be the most effective anti-glycating agent known.

Russian scientists set out to determine the effect of carnosine upon rats programmed to develop strokes. The first experiment focused upon carnosine as a revitalizer in hypoxic animals, i.e., those exposed to low oxygen levels. When oxygen-deprived animals were revitalized with normal levels of oxygen, the carnosine treated rats were able to stand after 4.3 minutes, as compared to 6.3 minutes in the untreated group.

In the second study, a stroke was simulated in the animals by arterial occlusion. The scientists found that carnosine acts as a neuroprotector in the ischemic (lack of oxygenated blood) brain. Rats treated with carnosine displayed more normal electrocardiograms, less lactate accumulation (a common measure of injury severity), and better cerebral blood flow. Suggested dosage: 1000-1500 mg daily. By taking at least 1000 mg a day of supplemental carnosine, the enzyme carnosinase (an enzyme that degrades carnosine) is overwhelmed. Carnosine should not be used during pregnancy or lactation.

CHONDROITIN SULFATE
Anti-inflammatory, antioxidant, inhibits LDL oxidation

Chondroitin sulfate is extremely popular in relieving the sore joints of osteoarthritis. In 1968, Dr. Lester Morrison began a 6-year study to determine its value as a cardio-protective. Dr. Morrison divided 120 patients with coronary heart disease into two groups, one group receiving chondroitin sulfate daily and the other a placebo. Lifestyles were not altered during the test period, i.e., all participants continued with their prescribed medication and appropriately designed diets. At the conclusion of the study, there had been 6 fatal heart attacks in the group taking the chondroitin sulfate; in the control group (those not receiving chondroitin), 42 fatal heart attacks had occurred, reflecting a 600% reduction.

In another study, 60 patients were given chondroitin sulfate, and a control group received a placebo. After two-years evaluation, 83% fewer coronary events had occurred among those receiving the chondroitin sulfate. Scientists speculate that the decrease in cardiovascular deaths would be staggering if chondroitin sulfate were routinely used by larger numbers of the population.

Chondroitin sulfate offers cardio-protection though its antioxidant activity, i.e., protecting against copper induced LDL oxidation, and its ability to inhibit inflammation. Suggested daily dose: (1-3) 400 mg tablets.

CHROMIUM
Modulates blood glucose levels, lowers cholesterol, aid in weight management

Of the sixteen minerals currently deemed essential, none play a more important role in blood glucose control than chromium. The benefits of chromium, a trace mineral, are not restricted, however, to modulating errant blood glucose levels. Obesity, coronary heart disease, hypertension, and hyperlipidemia, often, have a common denominator, insulin insensitivity, a condition that can be promulgated by a chromium deficiency. Approximately 90% of the adult population has a dietary deficiency of chromium that, eventually, terminates in some form of ill health.

One hundred eighty-eight people with type 2-diabetes participated in a study to determine the worth of chromium picolinate (CrP) supplementation in controlling unstable blood glucose levels. The individuals were divided into the following three groups: 1) received only a placebo, 2) received 200 mcg daily of (CrP) or 3) received 1000 mcg daily of CrP. The group receiving the larger dose of CrP reported near normal blood glucose and insulin levels after just four months of treatment; the other trial participants failed to report substantial improvement. The conclusion of multiple studies is that whenever glucose or insulin enters the bloodstream, chromium, inevitably, is needed to regulate too little or too much of either.

It is important to note that the type of chromium selected can influence the end results. For example, if chromium is to be used to counter obesity, chromium nicotinate (CrN) appears superior to chromium picolinate (CrP). The expected weight loss in individuals using CrN is between 1 to 2 kg, whether an exercise program accompanies chromium usage or not. It appears that CrP, without a co-commitment exercise program could result in weight gain.

Typically, chromium decreases total cholesterol by 10%, increases HDL by 2%, and decreases triglycerides by 17%. Suggested dosage: 200 to 400 mcg in divided dosages is, usually, considered adequate for most individuals; higher (supervised) doses may be required if used for type 2 diabetes. (Turn to niacin in the Therapeutic Section to read about the boost chromium gives to niacin, requiring less of vitamin B3 in lipid management.)

READERS GUIDE TO CHROMIUM FOOD SOURCES, ENHANCERS, and ANTAGONISTS
Brewer's yeast, brown rice, meat, corn oil, black pepper, whole grains, corn, dairy products, clams, eggs, mushrooms, and potatoes are sources of chromium. Selenium, vitamin E, and essential amino acids enhance absorption of chromium; iron opposes it.

COENZYME Q10
Lessens the incidence of angina attacks, arrhythmias, cardiomyopathy, congestive heart failure, heart valve irregularities, hypertension, mitral valve prolapse, and periodontal disease, protects LDL cholesterol against oxidation, increases exercise tolerance, burns unwanted fat, supports healthy cholesterol and triglyceride levels, beneficial to smokers

Coenzyme Q10 (CoQ10) can be synthesized in the body, but individuals with periodontal disease, cardiovascular disease, or hypertension, frequently, have inadequate levels. A significant finding is that cholesterol-lowering medications (as statin drugs) reduce CoQ10 levels. In a Swedish study, cardiac patients with low serum levels of CoQ10 had a very high predictable rate of death within six months.

Hypertensive patients (109 enrolled in the study) demonstrated a significant improvement while supplementing with CoQ10. At an average of 4.4 months, 51% of the patients were able to discontinue their blood pressure medication, noting about a 10% reduction in systolic and diastolic blood pressure.

The heart strengthening benefits of CoQ10 make it of significant value in the treatment of congestive heart failure (CHF). Depending upon the degree of cardiac impairment, CoQ10 can be used independently or added to traditional medicine.

Mol. Aspects Med reported the results of administering CoQ10 (50 to 150 mg daily) for 90 days to 2664 patients with CHF. (Baggio et al., 1994) The percentage of patients experiencing symptomatic and clinical improvement follow: cyanosis (bluish skin color) 78.1%, edema 78.6%, pulmonary edema 77.8%, dyspnea 52.7%, palpitations 75.4%, sweating 79.8%, arrhythmia 63.4%, and vertigo 73.1%. Fifty-four percent of the patients observed a concurrent improvement in several symptoms, which could be interpreted as an index of improved quality of life. A one-year study (involving 640 individuals with CHF) showed that patients using CoQ10 were healthier and required less hospitalization. (Moriscot et al.,1993)

Elsevier Science Publ. (Amsterdam) reported that the ejection fraction (how fully the heart pumps the blood out), end diastolic volume index (the adequacy of the heart to fill with blood), cardiac index (the amount of blood pumped out, considering body size), stroke volume (amount of blood pumped out on each beat of the heart) and cardiac output (the amount of blood pumped out per minute) all improved while using CoQ10. (Judy et al., 1984) The improvement observed in left ventricular function may prove valuable in preventing left ventricular depression following coronary artery bypass and valvular surgery.

The following examples reflects the breadth of CoQ10's credits:

	Exercise tolerance, typically, improves after 6 months of CoQ10 supplementation from 41% to 59%.
	The frequency of angina attacks, i.e., a squeezing or pressure like pain in the chest, usually provoked by exercise, decreases by about 53%.
	A reduction in complications following a first heart attack and the incidence of second attacks are, often, attributed to CoQ10 therapy.
	CoQ10 assists in repairing the heart muscle after a heart attack.
	CoQ10 stabilizes cholesterol and triglyceride levels.
	Anecdotal reports of individuals spared the rigors of a heart transplant have been credited to CoQ10.

Mitral valve prolapse (MVP) is a slight deformity in the valve, separating the left atrium from the left ventricle. Mitral valve prolapse, also called floppy valve syndrome, is a common condition associated with a heart murmur. Mitral valve prolapse is, often, asymptomatic but can produce chest pain, arrhythmia or leakage of the valve, leading to congestive heart disease. Four hundred children with MVP (ages 8-16) received CoQ10 (0.6-3.4 mg/kg/day). This dosage was effective in controlling symptomatic complaints, as well as improving stress-induced cardiac dysfunction. Relapse was common, however, among those who were noncompliant concerning dosing.

CoQ10, acting as a powerful antioxidant, can inhibit oxidation of LDL cholesterol. CoQ10 accomplishes this by attaching to LDL particles circulating in the bloodstream. Were there more riders (CoQ10) than carriers (LDL) the oxidation of LDL would be less worrisome.

CoQ10's antioxidant activity extends to protect the cells and lungs of smokers. By aiding oxygen delivery, reducing platelet aggregation, and regressing free radical activity, the brain and heart have, significantly, greater protection. In fact, CoQ10 assists other antioxidants in performing with greater efficiency. Recent studies indicate that CoQ10 is required for vitamin E to function to its full antioxidant potential.

Periodontal disease, a risk factor regarding heart health, responds to CoQ10 supplementation. Gingival pocket depth, swelling, bleeding, redness, pain, exudates, and looseness of teeth were significantly improved, using 50 mg of CoQ10 per day. (The herbs, goldenseal and echinacea, should accompany CoQ10 supplementation to further reduce oral infection.)

For the dieter, CoQ10 is "good news." Together with a well-planned dietary and exercise program, CoQ10 assists in shedding unwanted pounds.

CoQ10's ability to energize the heart is probably its chief attribute. The heart is one of the most metabolically active organs in the body, pumping approximately 2,000 gallon of blood through 65,000 miles of blood vessels, beating 100,000 times each day. The mitochondria (considered the powerhouse of the cell) are represented in large numbers (up to 2,000 mitochondria in each heart cell), providing the high-energy needed to fuel this unbelievable performance. The heart cells have more CoQ10 than any other cells, a supply critical to ATP production and cardiac function.

Despite the large body of clinical evidence demonstrating CoQ10 efficacy, tragically, the majority of cardiac physicians still disregard its potential. Dosage suggestions: 30 to 400 mg/day, depending upon the amount of cardiac support required. (Use CoQ10 in divided doses with meals containing fat; use larger doses under physician supervision.)

READERS GUIDE TO COQ10 FOOD SOURCES
Coenzyme Q10 appears in beef, mackerel, salmon, sardines, peanuts, and spinach.

CONJUGATED LINOLEIC ACID (CLA)
Aids in fat loss, reduces cholesterol and triglycerides, assists in utilization of beneficial fats, increases insulin sensitivity and antioxidant protection

Some researchers regard the principal causal factor of obesity to be a conjugated linoleic acid (CLA) deficiency. CLA can be obtained from dietary choices, as turkey, lamb, beef, and some fatty dairy products, but the current trend away from meats and fats has caused levels of CLA to meaningfully drop.

CLA has been reliable in regard to reducing body fat, while preserving lean body mass. CLA appears to benefit the dieter by increasing basal metabolic rate and impacting the distribution of fat, especially abdominal obesity. (Recall that apple-shaped bodies are considered vulnerable in regard to heart disease.) A Norwegian human study found that CLA-supplemented subjects lost up to 20% of their body fat in three months without changing their diet, while the control subjects, on an average, gained a slight amount of body fat during the same period.

CLA appears to modulate fat receptivity by encouraging insulin sensitivity. This mechanism allows fatty acids and glucose to migrate easily through muscle cell membranes and not into fat cells, a process that impacts the initiation and progression of heart disease, diabetes, and Syndrome X. CLA, also, has antioxidant activity and hypolipidemic properties, as well as the ability to inhibit the production of inflammatory leukotrienes by lowering levels of arachidonic acid.

Some question whether linoleic acid and CLA accomplish the same tasks. Though the two acids are related, they appear to oppose one another on factors that influence cardiac performance. While the linoleic acid cascade has a greater tendency to stimulate fat formation, CLA appears to inhibit it. Cholesterol is more likely to be oxidized by various factors working off the linoleic cascade, whereas CLA appears to stabilize cholesterol.

Laboratory animals, supplemented with CLA for 36 weeks at a dose 50 times higher than the suggested upper-range for human consumption, completed the study without signs of toxicity. Suggested dosage: three to six 500-mg capsules daily, in divided doses.

Curcumin
An anti-inflammatory, blood thinner, and hypocholesterolemic, inhibits platelet aggregation, protective to smokers

Curcumin, not to be mistaken for the herb cumin, is the yellow pigment of turmeric (Curcuma longa), found in mustard and curry powder. Curcumin has gained popularity because of its anti-inflammatory and blood thinning properties. Yet, its cardio-protection extends to altering blood lipid levels, particularly cholesterol. Rats fed 0.1% curcumin along with a cholesterol diet, had about one-half the blood cholesterol as rats fed equal amounts of cholesterol but without curcumin. (Lower dose curcumin appears more effective than higher doses in reducing LDL oxidation and triglycerides.) Curcumin addresses another of the cardiac risks (inflammation), by inhibiting leukotriene formation, promoting fibrinolysis, and discouraging platelet aggregation.

Curcumin is such a powerful antioxidant it is considered a protective for smokers, lessening free radical attack and cellular damage. Recommended dosage: 400 to 600 mg three times a day.

DHEA…Dehydroepiandrosterone + Nettle Leaf Extract
Anti-inflammatory, anti-lipidemic, increases hormonal levels, beneficial in diabetes and syndrome X

Low levels of DHEA hormones, the most abundant steroid in the human body, are correlated with inflammation and heart disease in men. DHEA delivers much of its protection by acting as a prohormone, meaning it can bolster lagging estrogenic or androgenic hormones. In fact, DHEA's value as an anti-lipidemic appears due, in part, to its ability to increase estrogen and testosterone levels. (Read about testosterone as a cardioprotective in the Therapeutic Section.) Studies show that DHEA even reduced the expected atherosclerotic build up in rabbits fed a high-cholesterol diet. Other antiatherogenic properties of DHEA include inhibiting the activity of fibroblasts, i.e., cells that proliferate at the site of chronic inflammation.

DHEA, by incorporating into HDL and LDL cholesterol, protects against their oxidation. With aging, cholesterol-bound DHEA becomes scarce, and compared to younger people with adequate levels of DHEA, oxidation rockets. Another hindrance involving antioxidant defenses occurs as superoxide dismutase, a powerful antioxidant, becomes lethargic as DHEA levels dwindle.

The Massachusetts Male Aging Study determined that in a sample analysis of 1,167 men, those with serum DHEAS (DHEA sulfate) in the lowest quartile at baseline (<1.6 microg/ml) were 60% more likely to incur ischemic heart disease. (Feldman et al., 2001) DHEA supplementation appears to deliver dramatic cardiac advantage to men; the bonus does not appear to extend to include women.

A study involving improved glucose control among diabetic rats (supplemented with DHEA) indicates it may be of benefit to diabetic patients. Syndrome X may, also, be responsive to DHEA, considering the inverse relationship between DHEA and insulin. In fact reducing carbohydrates to less than 40 g per day (recommendations reminiscent of the Syndrome X diet) resulted in a 34% increase in DHEA. Scientists ponder whether DHEA may be the missing link in the insulin resistance/hyperinsulinemia epidemic. Insulin appears to deliver its blow to DHEA by inhibiting production and stimulating clearance. (Nestler et al., 1992)

The inflammatory process in heart disease gives DHEA new dimension. Current studies show that increased inflammation in the elderly is correlated with a DHEA deficiency. For example, pro-inflammatory cytokines, i.e., interleukin-1B, interleukin-6 (IL-6) and tumor necrosis factor (TNF) rise with age resulting in higher levels of C-reactive protein and fibrinogen. DHEA suppresses the activity of IL-6 and the TNF, a process that inhibits inflammation and clot formation. JAMA reported that circulating IL-6 is a strong independent marker of increased mortality in unstable coronary artery disease patients, and identifies those who benefit most from a strategy of early invasive management. (Lindmark et al., 2001) Turn to C-reactive protein and Link Between Inflammation and Infection in Heart Disease (in this protocol) to learn more about the inflammatory process in heart disease.

Nettle leaf extract, also, appears effective in suppressing tumor necrosis factor alpha, plus interleukin-1B cytokines. Nettle leaf extract contains a variety of natural cyclooxygenase inhibitors, further reducing inflammation and the threat of heart disease. By contrast, the Archives of Internal Medicine reported that the use of non-steroidal anti-inflammatory drugs actually increased the likelihood of congestive heart failure from 2.5% to 26.3% in elderly patients. (Page et al., 2000)

Suggested DHEA dosage and caveats: 15 mg to 75 mg, taken early in the day. (50 mg represents a typical daily dose.) Blood tests are valuable at the onset and again 3-6 weeks into therapy to assist in assigning appropriate dosages. (Optimal DHEA levels for men are between 400-560 mcg/dL; for women the range is considered ideal at 350-430 mcg/dL.) Antioxidants, as green tea, vitamin E, and N-acetyl-cysteine, should accompany DHEA supplementation, though the threat of potentiating free radical activity appears roused only at much higher doses than what are needed to provide desired effects.

Because DHEA invigorates hormonal systems it is not recommended for men with prostate cancer or women with estrogen dependent cancer, without physician approval. (DHEA can be converted into testosterone and estrogen) Before starting DHEA therapy, men should know their serum PSA (prostate specific antigen) level and have passed a digital rectal examination. DHEA does not cause prostate cancer, but since DHEA can cause an increase in testosterone levels, the presence of an undetected cancer should be ruled out before initiating the therapy. Suggested nettle leaf extract dose: 300 mg used three times a day. Nettle leaf extract, also, exerts a diuretic action making it beneficial for hypertensive individuals and those with heart failure.

ESSENTIAL FATTY ACIDS
Inhibits platelet clumping, has antispasmodic activity, improves HDL/LDL ratio, lessens risk of second heart attack, stroke, and restenosis following angioplasty, inhibits cardiac arrhythmias, is hypotensive, reduces fibrinogen, Lp(a), C-reactive protein, total cholesterol, and homocysteine, improves insulin sensitivity, beneficial to dieters

The current mania, regarding low-fat diets, is contributing to deficiencies and imbalances of essential fatty acids, i.e., linoleic acid and alpha linolenic acid. The body cannot synthesize these fats and is dependent upon the diet for their supply.

Some individuals defend the premise that fats do little more than make you fat, and that they can be eliminated without upsetting metabolic processes. In truth, fats initiate the transmission of vital messages, in part, by programming activity in the omega-6 and omega-3 fatty acid cascades. Instruction received by prostaglandins (hormone-like substances produced from fatty acids), encourages some prostaglandins to oppose and others to neutralize, a process that holds the entire family in check.

Prostaglandins are found in virtually all cell membranes and control most metabolic functions. Vital as they are, when out of balance, they can prove the undoing of the host. For example, PGE2 is, generally regarded as a less desirable (even destructive) prostaglandin. (Though PGE2 can provoke an inflammatory response, the body does need some PGE2 to maintain the mucosal integrity of the intestinal wall.) On the other hand, PGE1 and PGE3 are good prostaglandins, meaning they decrease the likelihood of platelets clumping and dilate blood vessels, while exerting anti-inflammatory activity.

STANDARD AMERICAN DIET (SAD)
The standard American diet is high in saturated fats and arachidonic acid but, frequently, deficient in alpha linolenic acid, an omega-3 fatty acid. Many Americans have an omega-6 to omega-3 ratio of about 20:1. Clarifying our departure from primitive diets, ancient kinsmen maintained a ratio nearer 1:1. Mainstream recommendations for omega-6/omega-3 ratios are about 4:1, but a more ideal ratio appears to be nearer 2:1.

Dr. James Braley, M.D., cautions that a dietary departure from the omega-3 fatty acids can lead to an overproduction of PGE2, a pro-inflammatory, platelet-aggregating prostaglandin. For this reason, diet and supplementation should, most often, favor the lagging omega-3 fatty acids. (When the omega-3s are emphasized, arachidonic acid, the precursor to PGE2 goes down.)

Illustrative of the importance of having more good prostaglandins than bad, some researchers estimate that 30% or more of heart attacks occur as a result of smooth muscles in the walls of the coronary arteries going into spasm, causing disruption of oxygen supply to the heart. If oxygen cutoff is not long lasting, renewed delivery of oxygen begins and the spasm ceases. PGE1 dilates the blood vessels and PGE2 constricts the blood vessels. A dilated blood vessel is less prone to spasm. Compounding the problem, PGE2 is often released during heart spasm, further constricting the blood vessels.

Figure 5 illustrates the Omega-6 and Omega-3 cascades and the enzymes, delta-6-and delta-5-desaturase that spur sequential movement through the series. Recall that off arachidonic acid, the parent of PGE2, leukotrienes (a compound considered 1000 times more inflammatory than histamine) is formed.

Figure 5
Simplified View of The Omega-6 and Omega-3 Cascades

Omega-6-Series Omega-3-series

Cis-Linoleic acid (Cis-LA) Alpha-Linolenic acid (ALA)

__delta-6-desaturase__

Gamma-Linolenic acid (GLA)

Dihomogammalinolenic acid (DHGLA)

Prostaglandin E1

__delta-5-desaturase__

Arachidonic acid Eicosapentaenoic acid (EPA)
+ Docosahexaenoic acid (DHA)
Prostaglandin E-2

Prostaglandin E-3

A functional delta 6-desaturase enzyme is crucial in the control of blood pressure. An example of this occurred when two trial groups, selected from 25 non-obese participants with mild to moderate hypertension, were given either linoleic acid and alpha linolenic acid or their reduced forms, i.e., GLA (360 mg/day) and EPA (180 mg/day). The first group was delta-6 desaturase dependent; the second group was not. After 8 to 12 weeks, the group receiving the GLA and EPA had reduced their blood pressure by about 10%. Those in the first group, who lacked the activity of delta-6 desaturase necessary to supply GLA and EPA, experienced no hypotensive benefit. (Hiroyasu et al, 2001a) Diabetes, hypercholesterolemia, and nutritional deficiencies (zinc, vitamin B6, and magnesium) can inhibit delta-6 desaturase activity. Individuals with a sluggish delta-6 desaturase enzyme will need to use the fatty acid that appears downstream from the enzyme. (Figure 5 illustrates this sequence.)

MODULATES LIPIDS, BUT SO MUCH MORE…
Dr. Julian Whitaker suggested (in the summer of 2001) that grinding whole raw flaxseeds, sources of omega-3 fatty acids and lignans, and adding them to any cold food reduced cholesterol levels up to 100 points. Hundreds of studies indicate omega-3 fatty acids increase the beneficial HDL cholesterol while lowering total cholesterol and triglycerides, but raw flaxseeds appear to deliver exception anti-lipidemic qualities.

Women receiving 2.4 g/d of eicosapentaenoic acid (EPA) and 1.6 g/d of docosahexaenoic acid (DHA) reduced their triglycerides by 26%. Typically, both men and women observe an increase in HDL2, the most beneficial of the HDL subtypes, after 6 months of omega-3 fatty acid supplementation. Recall that individuals achieving longevity frequently display elevations in HDL2b cholesterol, representative of better cardiac function.

Evening primrose oil, high in gamma linolenic acid (GLA), has been shown to decrease LDL cholesterol, sometimes by as much as 50 mg. After 4 months, 12 hyperlipidemic men reduced their triglyceride levels by an average of 48% and increased their HDL cholesterol by 22%, taking 240 mg/day of GLA supplements. GLA inhibited platelet aggregation and combinations of evening primrose oil and fish oil decreased smooth muscle proliferation (a contributor to vascular closure).

Recent papers reported that eating coldwater fish (a good source of omega-3 fatty acids) 2 or 3 times per week could reduce the risk of sudden cardiac death by 30% to 40%. Obviously, there are mechanisms released through fish consumption that go beyond regulating cholesterol and triglycerides.

	Dr. Kilmer McCully, pioneer of the homocysteine/heart disease theory, determined that fish oil lowers homocysteine levels.
	Reports confirm that a diet that includes fatty fish results in a slight decrease in platelet adhesion and an increase in clotting time.
	Louisiana State University in Baton Rouge reported that fish oil decreases fibrinogen, a process that tends to thin the blood and make it less prone to clot.
	Omega-3 fatty acids have been shown to lower lipoprotein(a).
	Dr. Robert Atkins, a complementary physician with a background in cardiology, believes that fatty acids are natural defibrillators, lessening the incidence of cardiac arrhythmias and atrial fibrillation.
	Several years ago, the Life Extension Foundation reported that omega-3 fatty acids reduce the risk of second heart attack and stroke, by inhibiting cardiac arrhythmias, maintaining cardiac energy output, and reducing thrombosis.
	JAMA cited a 40% to 50% reduction in strokes among middle-aged women who did not use aspirin but ate fish four to five times per week. (Hiroyasu et al., 2001a)
	DHA reduced 24-hour blood pressure (5.8/3.3 mmHg systolic and diastolic) and daytime ambulatory blood pressure (3.5/2.0 mmHg). Another study showed that for every absolute 1% increase in body alpha-linolenic acid content there was a decrease of 5 mmHg in both systolic and diastolic blood pressure.
	DHA lowered norepinephrine, a gesture that protects the cardiovascular system by reducing vasoconstriction and blood pressure.
	Fish oils reduce C-reactive protein levels.
	It is theorized that EPA and DHA protect against the damaging effects of stress, another contributor to heart disease.

After angioplasty, 194 patients were randomly assigned to receive either 4.5 g/day of fish oil capsules (3,150 mg of eicosapentaenoic acid and 1,350 mg of docosahexaenoic acid for 6 months) or instructions to eat a low-fat (25% of total calories), low-cholesterol diet (100 mg per day) without fish oil. At the end of the trial, 36% of those not receiving the fish oil showed signs of restenosis (closure of previously opened arteries). The rate of restenosis in the fish oil group was about 19%. The study suggests, as do other trials, that high dose fish oil supplements may reduce the frequency of restenosis after successful coronary angioplasty. Dr. Mark Milner, M.D., lead researcher in the study, said, however, his preference for supplying omega-3 fatty acids was through fish consumption not fish oil. Milner cited increased numbers of intracerebral hemorrhages occurring among Eskimos whose diet contained large amounts of fish oil as the mitigating factor. (Milner et al., 1989)

BALANCE…ALWAYS THE KEY
The need for balance, regarding dietary fats, is clearly evidenced in a report appearing in the journal Circulation. (Hiroyasu et al., 2001b) It appears that very low levels of animal fat and protein increased the risk of hemorrhagic stroke in hypertensive women by 370% over women eating more dietary fat. The researchers also note that individuals with a very low intake of saturated fat may develop structural impairment of the arteries. Though saturated fats have been maligned for years, it now appears that some saturated fats, i.e., balance among the family of fats, are required for healthy arteries and a reduced risk of hemorrhagic stroke.

TRANS FATS
Technology can transform a benign fat into a dangerous food product. This occurs when fats are exposed to the hydrogenation process, i.e., saturating the oil with hydrogen to improve stability, taste, and odor. Heating oils at temperatures above 300 degrees F has the same effect.

Hydrogenation can turn liquid oils as corn, soybean, sunflower, sesame, and cotton into a semisolid shortening or margarine. This process changes a cis (a beneficial fat) to a non-functional form (a trans fat) that can no longer participate in prostaglandin production. Be aware that the harder the fat, the more trans fats it contains. This caveat includes Benecol, recommended by the AMA as a cholesterol-lowering margarine, which contains trans fatty acids from processed soybean oil. Hydrogenated fats, also, deliver serious blows by reducing activity in the omega-6 and omega-3 cascades (probably by inhibiting the enzyme, delta-6 desaturase); LDL cholesterol is raised but HDL cholesterol is lowered.

A study, involving 600 men (ages 64 to 87) determined that for every 2% increase in trans fatty acids (considering total energy intake), the risk of developing coronary heart disease increased over the next 10 years by 25%. (Oomen el al., 2001) The influence of different types of fats can, also, be observed in the progression of diabetes. For example, the risk of diabetes was not increased among 84,000 women whose intake of fats came chiefly from nuts, seeds, and avocados, but a 2% increase in trans fatty acids raised the risk by 39%. A 5% increase in polyunsaturated fats lowered the risk of diabetes by 37%.

In 1993, doctors at Harvard Medical School found that women who ate 4 or more teaspoons of margarine a day had a 50% greater risk of developing heart disease compared to women who ate margarine only once a month. Though the amount of trans fatty acids appearing in margarines and shortening has been reduced in the U.S., these damaging fats are still found in many other foods, as bakery items and fast food products. (Trans fats become a major part of American diets, when the 30 pounds of French fries consumed per capita are factored into dietary analysis.) Trans fats often hide on dietary labels as partially hydrogenated fat or vegetable oil. Learn to read labels and avoid them.

Growing public awareness regarding the dangers imposed by trans fats has prompted a reduction in their consumption. An example of the benefits of eliminating trans fatty acids from the diet comes by way of a study released from The Netherlands. An average 2.4% drop in fatty acid consumption appears to have prompted a 23% decrease in coronary deaths and saved, it is speculated, about 4600 lives.

BENEFICIAL TO DIETERS
Studies have shown that genetically obese people profit from essential fatty acid supplementation. The weight loss in these individuals is gradual but reliable, even among those considered intractably obese.

Evening primrose oil, rich in gamma linolenic acid, appears to stimulate brown fat cells, by producing PGE1. Brown fat is of particular advantage in maintaining a desirable weight because it uses extra calories to provide heat, preventing the deposit of unsightly white fat. Brown fat's energy-use capacity accounts for major differences between brown fat and white fat. Mitochondria, fat burning units, are abundantly dispersed throughout brown fat cells.

Brown fat is found primarily attached to large blood vessels in the thoracic cavity, along certain ribs, the nape of the neck, armpits, and between and below the shoulder blades. Individual differences in amounts of brown fat have been theorized to account for the ability (or inability) to maintain a desirable weight. Without sufficient amounts of brown fat, calories are not burned and, as a result, overweight individuals may actually gain weight on fewer calories. As a weight deterrent, it appears essential fatty acids most benefit those who are more than 20% overweight.

SYNDROME X (metabolic syndrome) AND DIABETES
Omega-3 fatty acids maintain flexible cell membranes. This is important, for healthy membranes contain large numbers of insulin receptors, increasing the surface areas available for insulin binding, important in diabetes and Syndrome X.

Metabolic syndrome-induced rats, i.e., those fed a high sugar diet, showed a significant increase in systolic blood pressure, blood insulin, triglycerides, and blood cholesterol levels. When an omega-3 enriched diet was fed for 6 weeks, the rats had a significant reduction in blood pressure, blood insulin, and triglyceride levels. Those rats receiving an omega-6 rich diet reduced triglycerides.

WHAT ARE THE GOOD FATS?
Individuals wishing to increase their consumption of beneficial fish and marine life should consider herring, mackerel, sea bass, salmon, cod, sardines, tuna (fresh), whitefish, coldwater halibut, and anchovy, varieties especially high in eicosapentaenoic acid (EPA). From the plant kingdom, walnuts and most beans are, also, sources of omega-3 fatty acids.

It should be noted that prothrombin times, usually, remain within a normal range when using the omega-3s. As the number of platelets decrease, platelet size, typically, increases; therefore, there is no overall decrease in platelet mass. The New England Journal of Medicine reported that the blood thinning functions of fish oil are small compared to aspirin, but other researchers caution that bleeding time could increase to inappropriate levels if baseline platelet activity was impaired or fibrinogen concentrations low. (Katan, 1995)

Olive oil, an omega 9-fatty acid (a monounsaturated fat) is an excellent choice for both salads and cooking. It is extremely difficult, however, to purchase oils in an ideal state; if shopping from a supermarket, a better choice appears to be extra virgin olive oil in a lightproof container. (Refrigerate the oil, once home.) Other sources of omega-9's are almonds, pecans, cashews, filberts, and macadamias. Omega-9's contribute primarily to the structural elements of phosphatides; phosphatides are essential to healthy cell structure.

Almond oil is currently reviewed better than canola oil (rape seed) by various practitioner/researchers. Canola oil is derived from seeds of a plant (considered, by some, toxic), belonging to the mustard family. Canola oil, when processed, appears to become rancid very quickly, and may over time increase the risk of respiratory illness and the incidence of heart disease. Refrigeration does not retard its oxidation. Canola oil proponents still uphold its value, but until more questions are answered regarding its safety, it seems wiser to select the tried and true olive oil.

According to Robert Erdmann, Ph.D., butter, in small amounts, is a better choice than margarine. He credits butter as not only being highly nutritious but, also, as being an under exploited form of alternative health therapy.

SUPPLEMENTAL OMEGA 6 AND OMEGA 3 FATTY ACIDS…WHAT TO BUY
To introduce the reader to various omega 6 and omega 3 fatty acids, the following examples are given: perilla oil, 1,000 mg capsules, provides 550-620 mg of alpha-linolenic acid, a precursor to EPA and DHA. Use three to six softgels daily. Flaxseed oil (1000 mg softgels) is a rich source of omega-3 fatty acids. Use one to six softgels per day. If fish oils are used, the dosage is 1200 to 2400 mg/day. Evening primrose oil is a source of gamma-linolenic acid (GLA). Use one to two 1300-mg softgels daily. Borage oil, also, supplies GLA. (A 1300 mg softgel supplies 300 mg of GLA). As a preventative, use 1-2 softgels per day and up to 5 softgels as a therapeutic. Administering a combination (3 grams) of eicosapentaenoic acid and the omega-6 fatty acid, GLA, appears to prevent arachidonic acid accumulation, a trigger in the inflammatory process.

FIBER
A hypolipidemic and antidiabetic agent, aid to weight loss, blocks iron absorption

The intake of dietary fiber among people living in Western countries is low (about 17g a day in the U.S.), according to the Third National Health and Nutrition Examination Survey (NHANES). This is unfortunate for soluble fiber offers significant protection against a number of risk factors associated with cardiovascular disease. For example, soluble fibers including mucilages, guar gum, psyllium powder, oat bran, and pectin reduce cholesterol levels. Guar gum (5 gram/meal), psyllium powder (5 grams/before meals), and pectin (10 gram/meal) reduce fasting and postprandial blood glucose, as well as insulin levels in both healthy and diabetic subjects. If taken with meals, soluble fibers (6 to10 g/day) reduce iron absorption from foods, important to those with hemochromatosis or iron overload. (To read about hemochromatosis as a contributor to cardiovascular disease, turn to Iron Overload in the section devoted to Traditional Risk Factors).

Illustrative of the benefit of fiber, 125 patients (average age 57 years) with type II diabetes were enrolled in a double-blind placebo-controlled six-week trial. (Rodriguez-Moran et al., 1998) The participants were advised to obtain 40% to 50% of total calories from carbohydrates, 1.0 g/kg per day of protein, and the balance of the diet from polyunsaturated fats. Patients were then randomly assigned to receive 5 grams of Plantago psyllium powder in 250 mL of water before meals or a placebo, three times a day. The following laboratory changes were observed during the course of the trial: mean plasma glucose levels dropped from approximately 175 mg/dL to 140 mg/dL, total cholesterol, triglyceride and LDL values dropped from 221 to 195, 186 to 137 and 146 to 118, respectively. HDL levels increased from 34 to 51. These dramatic results occur as fiber binds bile acids, cholesterol, and fats, preventing their absorption. Short chain fatty acids, a product of fiber fermentation in the colon, further inhibits cholesterol synthesis by the liver.

Studies published in the NEJM confirmed the value of a high fiber diet in improving glycemic control, reducing hyperinsulinemia and plasma lipid levels in patients with type 2 diabetes. (Chandalia et al., 2000) In a randomized, 6-week crossover study, 13 patients with type 2 diabetes mellitus were given diets containing either moderate or high amounts of fiber. During the first six week' s evaluation, the fiber allowance was 24 g (8 g of soluble fiber and 16 g of insoluble) an amount compliant with guidelines established by the ADA. The second six weeks of the trial, the patients were given 50 g of fiber (25 g soluble and 25 g insoluble). Foods, rich in fiber, were prepared in a research kitchen and included cantaloupe, grapefruit, raisins, orange, papaya, lima beans, okra, sweet potato, winter squash, zucchini, oat bran, and oatmeal.

The results indicated that more fiber was better than less. The diet supplying 50 g/day of fiber lowered plasma glucose by 10%, insulin concentrations by 12%, total cholesterol by 6.7%, triglyceride levels by 10.2%, VLDL by 12.5%, and LDL cholesterol by 6.3%. It is speculated that the decrease in triglycerides and VLDL may be due more to improved glycemic control than a direct relationship with the fiber. There was no significant difference between the two diets in terms of HDL cholesterol.

Fiber is of advantage to individuals who wish to lose weight, for bulk tends to render a feeling of fullness. Satiety negates the desire to overeat. An overweight individual should consider using bulk fibers stirred into an 8-ounce glass of water; drink the mixture about 20 minutes before meals.

Diabetics and those not accustomed to higher levels of fiber should, initially, use the substance cautiously. Fiber can, significantly, alter insulin or sulfonylurea requirements. Some individuals experience gastrointestinal distress until the GI tract becomes better acquainted with the new material. Suggested dosage: Begin with one teaspoon daily; gradually increase to one teaspoon, three times daily.

Readers guide to foods high in fiber: Grains are excellent sources of fiber, but many individuals find the addition of cereal grains problematic due to sensitivities. Vegetables and fruits (raw and with peel in tact) are pleasant fibrous additions to the diet.

GARLIC
Acts as a hypotensive, decreases fibrinogen, inhibits platelet aggregation, thins the blood, lowers cholesterol, protects against LDL oxidation, reduces the incidence of arrhythmias, modestly reduces blood glucose levels, protects against iron overload, is vasodilating

The consensus surrounding the benefits of garlic as a hypolipidemic is not unified. The Agency for Healthcare Research and Quality reported that garlic appeared to supply only short-term benefits in regard to lipid management. (Report Number 20) The report acknowledged that variations in garlic preparations could be distorting results.

The American Journal of Natural Medicine reported that 4,000 mg of fresh garlic (guaranteeing an alliin content of at least 10,000 mcg or a total allicin yield of 4,000 mcg), typically, lowered total cholesterol levels 10% to 12%, triglycerides by about 15%, LDL by 15%, while increasing HDL levels by 10%. (Murray, 1995a)

Healthy human volunteers given 600 mg/day of a garlic preparation providing 7.8 mg of alliin for two weeks had a 34% lower susceptibility to lipoprotein oxidation compared to controls. It should be noted that garlic could cause a transient elevation in blood lipids, as garlic unseats fats deposited in tissues. With continued garlic supplementation, lipid stores complete the breakdown process and blood cholesterol levels modulate.

While much of the research has focused on improving lipid levels, studies have isolated hypotensive factors in garlic, as well. In human studies, garlic decreased systolic pressure by 20-30 mmHg and diastolic by 10-20 mmHg. Garlic, a sulfur-rich plant from the lily family, exerts its hypotensive nature through the following mechanisms:

	Garlic modulates activity occurring in the sympathetic nervous system, which when aroused, increases blood pressure.
	Garlic inhibits the activity of the angiotensin-converting enzyme (ACE), an enzyme that increases blood pressure by catalyzing the conversion of angiotensin I to angiotensin II. This sequence constricts blood vessels, conserves water and sodium ions, and unless interrupted, results in an increase in blood pressure.
	Garlic increases the activity of nitric oxide synthase, an enzyme essential for nitric oxide synthesis. Nitric oxide, a relaxing factor, not only reduces blood pressure by acting as a vasodilator, it also lessens platelet aggregation, suppresses smooth muscle proliferation, reduces leukocyte adherence to vessel walls, and has antianginal/antispasmotic activity.

Garlic exhibits additional cardiovascular protection by thinning the blood and acting as a fibrinolytic. German researchers have reported successes in treating arrhythmias with garlic supplementation, lessening the incidence by 88%. Garlic modestly reduces blood glucose levels. EDTA/garlic capsules appear to decrease iron stores, while protecting tissue. Dosage suggestion: a garlic supplement equivalent to 4,000 mg of fresh garlic per day.

GINGER
Reduces cholesterol, thins the blood, prevents blood clots, is an anti-inflammatory

Ginger, Zingiber officinale, is reliable in treating a wide variety of cardiovascular complaints. Among ginger's protective properties is its ability to reduce cholesterol by promoting cholesterol excretion, impairing cholesterol absorption, and encouraging bile secretion and bile acid production. Ginger exerts some of its hypolipidemic effects by stimulating cholesterol-7-alpha-hydroxylase, a rate-limiting enzyme of bile acid synthesis.

J Ethnopharmacol reported the effects of administering ginger (200 mg/kg/ orally) to 61 cholesterol-fed rabbits. (Bhandari et al., 1998) The marked rise in cholesterol, triglycerides, lipoproteins, and phospholipids, which normally follows 10 weeks of cholesterol feeding, was significantly reduced by ginger. The favorable results obtained from ginger were comparable to the hypolipidemic effects of the drug Lopid, known generically as gemfibrozil.

Ginger reduces the likelihood of blood clot formation through the following mechanism:

	Ginger, ginkgo, turmeric, and garlic share a common trait, i.e., the ability to inhibit the platelet-activating factor, PAF. Adequate amounts of PAF are essential to coagulation and inflammatory processes; excesses are associated with blood clot formation, stroke, and heart disease.
	Thromboxane A-2, a platelet-aggregating factor, is inhibited more by ginger than either garlic or onions.
	Prostacylin, an inhibitor of platelet aggregation, is pressed into service by ginger, a process that further reduces the likelihood of blood clot formation.

All of these effects are similar, i.e., reducing the risk of a blood clot, while thinning the blood. A study, involving healthy volunteers, showed no irregularities, however, in blood coagulation among participants receiving 2 gram of ginger per day. Nonetheless, caution is indicated for those individuals with baseline disturbances in platelet numbers or prothrombin time. Also, the activity of prescribed blood thinners may be heightened if used in concert with ginger.

Ginger, also, appears to protect the heart during periods of inflammation. (Recall that inflammation is considered a potential trigger in heart disease.) Ginger's anti-inflammatory properties are due to interruption of the prostaglandin/leukotriene cascade, blocking certain prostaglandins, but leaving beneficial prostaglandins unaffected. Ginger root (gingerols) has been shown to inhibit cyclooxygenase pathways, sharing anti-inflammatory status with other popular Cox-2 inhibitors. Dosage suggestions: one to two 300-mg capsules, one to three times a day. Note: JAMA published an article raising a cautionary flag concerning the risk of cardiovascular events occurring among users of Cox-2 inhibitors (as Celebrex and Vioxx). (Mukherjee et al., 2001) The FDA has objected to claims and promotional activities by Pharmacia Corporation minimizing the potentially serious risk of significant bleeding associated with the concomitant use of Celebrex and warfarin. (Fort, 2001) It is hoped further prospective evaluations will characterize and determine the magnitude of the risks. In the interim, natural COX-2 inhibitors loom as a welcome alternative.

GINKGO BILOBA
Improves circulation and memory, reduces platelet aggregation and excesses of fibrinogen, has antioxidant and antiinflammatory activity, prevents capillary fragility, lessens angina attacks, dyspnea, and intermittent claudication, limits brain damage following stroke, increases insulin secretion, is a vasodilator

Ginkgo biloba is one of the oldest surviving species on earth. But, this ancient herb, renowned for its ability to retard aging, has survived the test of time and is yielding remarkable benefits for millions of Americans and Europeans. Heart, circulatory, and cognitive disorders are the principle reasons individuals rely upon ginkgo. Substantiation of its benefits follows:

	Ginkgo has won favor among the Chinese as a heart tonic, by lessening coronary demands for oxygen, thus reducing shortness of breath and angina pain.
	Ginkgo's antioxidant properties assist in strengthening blood vessel walls and improving tone and elasticity.
	Ginkgo is a vasodilator, making it useful in lowering blood pressure and treating many forms of heart disease. (120 mg/day at bedtime for three months reduced systolic blood pressure from 125 +/- 15 to 118 +/- 12 mmHg and diastolic from 86 +/-10 to 68+/- 10 mmHg.) (Kudola, 2000)
	Ginkgo is an anti-inflammatory, adding additional merit to its cardio-profile. Consult the section entitled Link Between Infections and Inflammation in Heart Disease (in this protocol) to comprehend the value of anti-inflammatories in a comprehensive cardiovascular program.
	Ginkgolide B infusions are comparable to standard anti-arrhythmic drugs, in controlling irregular heartbeats.

In more than 50 double-blind clinical trials, patients with chronic cerebral vascular insufficiency have responded to Ginkgo Biloba extract (GBE). Subjective improvement in vertigo, headache, ringing in the ears, and memory are, commonly, reported when dosing with GBE.

GBE also, significantly improves the supply of blood to the limbs. As resting blood flow and peripheral circulation improve, intermittent claudication, a cramp-like pain in the calves, diminishes. In fact, 40 mg of GBE twice a day is more effective at controlling intermittent claudication than pentoxyfilline (Trental). Improved limb circulation increases periods of pain-free walking by 75% to 110%. Trental increased pain-free walking distance by only 65%.

Varro Tyler, Ph.D., dean and professor emeritus at Purdue University, endorses ginkgo in his book Herbs of Choice, as a treatment for stroke. Ginkgo can, also, act as a prophylaxis against strokes by reducing fragility of capillaries and counteracting erythrocyte and platelet hyperaggregability. The nature of platelets is strongly influenced by the platelet-activating factor (PAF), which ginkgo inhibits.

The American Academy of Neurology reported that ginkgo reduced the extent of brain damage caused by artificially induced strokes in mice. (June-July 2000 Edition) Mice receiving low-dose GBE one week prior to stroke reduced the area in the brain affected by 30%. The journal Stroke concurred that Ginkgo biloba extract reduced stroke infarct volume, but noted the beneficial effect appears to be dose related; higher doses, actually, appeared to increase the risk of intracerebral hemorrhage. (Clark et al., 2001)

The J Clin Pharmacol reported a function of ginkgo biloba not frequently credited to the herb, i.e., an ability to increase insulin secretion. A study was undertaken to determine the effect of ginkgo biloba extract on glucose-stimulated pancreatic beta-cell function in normal glucose-tolerant individuals. Twenty participants (14 females and 6 males, ages 21-57 years) underwent a 2-hour 75-g oral glucose tolerance test before and after ingestion of ginkgo biloba extract (120 mg/day at bedtime). During the 3-month evaluation, both fasting plasma insulin and C-peptide (a biologically inactive residue of insulin formation) increased. Dr. Kudolo (principal researcher) believes the changes in the insulin/C-peptide response curves is due to increased production and secretion of insulin, as well as a ginkgo biloba-induced increase in the rate of insulin clearance (Kudolo, 2000) Note: Herbals that influence glycemic control by increasing insulin secretion would be contraindicated in cases of existing hyperinsulinemia. If insulin production declines to the point that hypoinsulinemia exists, herbs that encourage insulin release would then be appropriate.

High quality GBE is typically standardized to contain a minimum of 24% ginkgo flavone glycosides and 6% terpene lactones. Side effects are rare when using the standardized extract; however, concomitant use with an anticoagulant medication or administering GBE to individuals with prolonged prothrombin time may make ginkgo biloba inappropriate. (Ginkgo is not recommended for pregnant or lactating women.) Dosing suggestions: 120-240 mg daily. 120 mg/day assists in reducing excessive fibrinogen levels, i.e., greater than 300 mg/dL.

GRAPEFRUIT PECTIN
Hypocholesterolemic

Grapefruit pectin, a stringy white fiber, appears equal to or greater than most popularly prescribed drugs for lowering cholesterol. A major difference emerges, however, when side effects are compared. Grapefruit pectin has no known side effects, a vast departure from the potential risks associated with statin drugs.

The following animal study illustrates the cholesterol lowering effects of grapefruit pectin. Researchers fed an atherogenic diet to a group of guinea pigs for one year. One half of the pigs were then fed pectin. More than a 40% reduction in cholesterol occurred during a 6-week period, and at the conclusion of the study, the pectin-fed pigs had decreased their arterial plaque by 88%. It was concluded that grapefruit pectin and other food sources rich in soluble fibers are useful adjuvants in the treatment of hypercholesterolemia.

Human trials have also, been gratifying. Subjects participating in the studies used no other cholesterol lowering agents and did not alter their exercise or dietary regime. Still significant improvement in cholesterol levels resulted.

Dr. James Cerda, M.D, has developed a highly soluble protein-pectin-guar gum product for the purpose of cholesterol reduction. The pectin breaks down in the small intestine so that 100% of the fiber is utilized. Begin with less than one scoop (with meals) and gradually increase until 2 to 3 scoops are used daily. If using grapefruit pectin tablets, use 1000 mg with meals.

GUGULIPID
Lowers total cholesterol, LDL and triglycerides, increases HDL cholesterol, regresses plaque formation, opposes platelet aggregation, has fibrinolytic activity

Numerous studies have shown that gugulipid is beneficial to 70% of individuals with disorganized lipid profiles, i.e., those showing elevations in LDL, total cholesterol, or triglycerides. Human clinical trials showed gugulipid dropped total cholesterol levels 14-27% in a 4-12 week period and triglyceride levels by 22-30%. LDL cholesterol was reduced by an average of 17%, making the effectiveness of Gugulipid comparable to 20 mg of fluvastsin or 10 mg or pravastatin. Gugulipid therapy, typically, increases HDL by 20-36%, comparable to 2 gram of niacin. It outclasses the prescription drugs cholestyramine, gemfibrozil and lovastatin in reducing total cholesterol and triglycerides, while increases HDL production. In addition, Gugulipid regresses plaque formation, opposes platelet aggregation, and encourages fibrinolysis. All of this is accomplished without threat of side effects. (ACCM Health Sense August 2001 Vol VII Issue 8.) Suggested dosage: 500 mg three times per day, having a 5% guggulsterone content.

HAWTHORN BERRY (Crataegus oxyacantha)
Normalizes blood pressure, beneficial to dieters and those with congestive heart failure, prevents premature ventricular contractions and hypoxia, has diuretic and antioxidant potential, lowers cholesterol, acts as a vasodilator, ACE inhibitor, beta-blocker, and anti-inflammatory, increases exercise tolerance

Dr. James Duke, botanist, says that when hawthorn is evaluated chemically, it appears the herb covers most of the cardiovascular bases. For example, it contains a calcium-antagonist (magnesium), ACE inhibitors (procyanidins), beta-blockers (catechin, epicatechin, and procyanidins), plus numerous diuretics, cholesterol lowering compounds, anti-inflammatories, and antioxidants.

Hawthorn berry is considered a "smart herb" with adaptogenic qualities in regard to normalizing blood pressure. Hawthorn gains much of its hypotensive/weight management properties through its diuretic action, i.e., ridding the body of excess salt and water. Also, ACE inhibiting factors, contained in hawthorn, interrupt the renin-angiotensin sequence, resulting in lower blood pressure and improved cardiac output. Physicians compare the effectiveness of hawthorn to Captopril, a drug prescribed for congestive heart failure and hypertension that works by inhibiting the angiotensin-converting enzyme (ACE). (Hawthorn, though helpful in blood pressure management, should not be regarded as the sole therapeutic for hypertension.)

The bioflavonoid content of hawthorn appears responsible for much of the herb's cardiac potential, i.e., dilating blood vessels, enhancing vitamin C absorption, and protecting against vascular breaks or leaks. Bioflavonoids are powerful antioxidants that not only protect against free radical damage but, also, increase the flow of oxygen and blood to the heart. This reduces the effort and stress imposed upon the heart to circulate blood, and as an additional bonus, a reduction in blood pressure, usually occurs.

During the Middle Ages, hawthorn was used to treat dropsy, a condition now recognized as congestive heart failure (CHF). Today, European physicians still use hawthorn to treat early signs of CHF, relying upon the herb to strengthen the heart and the power of cardiac contractions. Drugs that have the ability to "power up" the heart can cause cardiac irregularities. It appears hawthorn can energize the heart without prompting arrhythmias.

Studies confirm the multiplicity of hawthorn's actions. For example:

	Hawthorn has the ability to protect the heart from premature ventricular contractions and hypoxia (a condition of low oxygen) that, commonly, leads to angina.
	Findings recorded in Phytomedicine indicate that 78 patients given hawthorn for 56 days increased their exercise capacity over 500%. Problem-free exercise occurs as the heart becomes stronger and less taxed by exertion.
	Hawthorn, also, reduces cholesterol levels and the size of existing atherosclerotic plaque.

Hawthorn is best-used long term because the active constituents do not produce rapid results. It may take 4 to 8 weeks for improvement in subjective complaints and increased exercise tolerance. Though, it is regarded as gentle and safe for chronic usage, a physician should evaluate the patient's drug list before adding hawthorn to the total package. Dosage suggestions: 250-900 mg daily.

HOMOCYSTEINE LOWERING NUTRIENTS AND ELIMINATION PATHWAYS
Homocysteine, a naturally occurring amino acid, is derived from methionine and produced in small amounts by the body. When homocysteine is not detoxified or reduced through metabolic processes, (i.e., remethylation or transsulfuration) and begins to accumulate, trouble is apparent. According to some experts, homocysteine buildup is now recognized as the single greatest biochemical risk factor for heart disease. (For an Introduction to Homocysteine, consult material appearing under Novel Risk Factors.)

Published literature emphasizes that folic acid, vitamin B12, vitamin B6, zinc, (nutrient co-factors) and trimethylglycine (a methyl donor) are critical to the remethylation of homocysteine. The remethylation process occurs as methyl groups are donated to homocysteine to transform it to methionine and S-adenosylmethionine (SAMe). (SAMe, the chief methyl donor, is crucial to the methylation process.)

Initially, methionine reacts with ATP to produce SAMe. SAMe is then used for methylation and a by product of this reaction, homocysteine, is recycled back to methionine. This cyclic dance continues faultlessly, unless something throws it out of sync.

Too much methionine will disrupt the delicate balance. Flesh foods and dairy products are rich in methionine and require greater amounts of nutrient co-factors to preserve the methylation process, particularly vitamin B6. Chronic inflammation, high intensity exercise, and age can, also, put the brakes on methylation. When this occurs, the cycle is broken and homocysteine detoxification stagnates. The problem comes full circle, as excessive amounts of homocysteine interfere with the methylation process.

Trimethylglycine (TMG), also, called betaine, emerges as one of the most important nutrients to prevent and reverse existing heart disease. TMG delivers its cardiac advantage by acting as a potent remethylation agent. Betaine supplementation (TMG) usually causes a substantial lowering of homocysteine but regular dosing must continue to sustain the improvement. The dosage varies from one to eight 500-mg tablets/day, depending upon the amount needed to maintain healthy levels, i.e., below 7 micromol per liter of blood.

Choline, another methyl donor, can act independently to lower homocysteine levels, but it only influences remethylation in the liver and kidneys, leaving the heart and brain less protected. Methylating factors, as vitamin B12 and folic acid, add additional protection.

The second means of homocysteine disposal is via the transsulfuration pathway, a sequence dependent upon vitamin B6. This pathway converts homocysteine to the powerful antioxidants cysteine and glutathione, but a deficiency of the B6-dependent enzyme, cystathione-B-synthase, can hamper this process. An alternative is to take larger doses of vitamin B6, but this course is not without risk. Chronic mega dose vitamin B6 supplementation (300 to 500 mg daily) can result in neurological symptoms that, typically, fade when the dosage is reduced or discontinued. Careful monitoring to determine the lowest vitamin B6 dose capable of controlling homocysteine levels is essential.

Some individuals lack the enzyme necessary to convert vitamin B6 into its active form. In this case, use the biologically active pyridoxal-5-phosphate to control elevations in homocysteine. Note: Vitamin B6 is, also, a reliable diuretic, making it of particular advantage to patients with high blood pressure and congestive heart failure.

Hyperhomocysteinemia, for most individuals, is a modifiable cardiovascular risk factor. In fact, about one half of individuals with hyperhomocysteinemia respond favorably to vitamin B6 supplementation; another 20% have a mutation in the gene, methylenetetrahydrofolate reductase, disrupting the conversion of folic acid to 5-methyltetrahydrofolate, an active contributor in the methyl donation pathway of folate. In this incidence, it is necessary to use 5-methyltetrahydrofolate supplementation to remove the metabolic block. (Additional information regarding 5-methyletrahydrofolate appears in the Genetic Section under Traditional Risk Factors in this protocol.)

Researchers selected 421 patients, mildly hyperhomocysteinemic, to determine their response to vitamin B6 (250 mg daily). After 6 weeks of vitamin B6 supplementation, 56% of the patients had normal homocysteine levels. Non-normalized homocysteine concentrations were treated with a combination of supplements, i.e., vitamin B6 (250 mg daily) and/or folic acid (5 mg daily) and/or TMG (6 gm daily) solely or in combination. The more aggressive treatment normalized homocysteine levels in 95% of the remaining cases.

A Polish study showed that administering folic acid (5 mg/day), vitamin B6 (300 mg/day), and B12 (1000 microgram/day) over an 8-week period reduced benchmark homocysteine levels by one-half (from 20 to 10 micromoles/liter) and also reduced thrombin, an intermediate in the production of fibrinogen. (Undas, et al., 1999) It has been theorized that properly administered folate might prevent as many as 30,000 premature deaths, annually. Individuals with low folate status, regardless of age or sex, have a 69% increase in the risk of fatal coronary heart disease compared to individuals with higher levels, i.e., > 13.6 nanomoles per liter.

The NEJM reported that treatment with a combination of folic acid, vitamin B12, and pyridoxine significantly reduced homocysteine levels and decreased the rate of restenosis and the need for revascularization of the target lesion after coronary angioplasty. The researchers concluded that this inexpensive treatment, with minimal side effects, should be considered as adjunctive therapy for patients undoing coronary angioplasty. (Schnyder et al., 2001)

The American Journal of Clinical Nutrition reported that a chemical component of coffee and black tea (chlorogenic acid) can raise serum homocysteine levels. (Olthof et al., 2001) Individual's hyperhomocysteinemic may wish to restrict high intake of these beverages. Conversely, a diet rich in fruits and vegetables may reduce the risk of heart disease (7% to 9%) by reducing blood levels of homocysteine. Foods not exposed to the milling process have a more reliable nutrient bank and are capable of delivering more homocysteine-lowering vitamins and minerals. On the other hand, supplemental nicotinic acid (1 gram per day) actually raised homocysteine levels 1.5 mg/dL and depleted S-adenosylmethionine (SAMe), a key methyl donor.

Administering homocysteine-lowering nutrients is so individualized that testing is essential to determine adequate dosages. To assume that homocysteine is not a threat (because you have the B vitamins in your supplemental protocol) is not a guarantee that the dosage is appropriate to render protection. Dosage suggestions: the following daily supplements (used alone or in combination) have demonstrated homocysteine lowering effectiveness: 500 to 9000 mg of TMG, 800 to 5000 mcg of folic acid, 1000 to 3000 mcg of vitamin B12, 250 to 3000 mg of choline, 250 to 1000 mg of inositol, 30 to 90 mg of zinc, 100 to 500 mg of B6 and 200 to 800 mg of SAMe. (SAMe is of value in lowering homocysteine levels only if folic acid and vitamins B6 and B12 are also present. Without nutrient cofactors, SAMe will eventually breakdown into homocysteine). Note: JAMA reported that pretreatment with vitamins E and C (before an oral methionine load to experimentally increase homocysteine) blocked the damaging effects of hyperhomocysteinemia. Parameters monitored were coagulation, glucose, circulating adhesion molecules, blood pressure and endothelial function. (Nappo et al., 1999)

READERS GUIDE TO FOOD SOURCES, ENHANCERS and ANTAGONISTS TO HOMOCYSTEINE-LOWERING B VITAMINS: It should be noted that medications to treat congestive heart failure commonly result in multiple deficiencies in B vitamins, disrupting disposal systems for homocysteine clearance. (Sinatra, 2001) Also, the B vitamins are considered unstable when exposed to the heating process, but the following foods represent the most nutrient dense choices.

VITAMIN B6 appears in most foodstuffs but the best sources are brewer's yeast, wheat germ, pork, organ meats (especially liver), whole grain cereals, legumes, potatoes, bananas, and oatmeal. Other sources include most beans and fish, avocadoes, and egg yolk.

Complimentary nutrients in regard to vitamin B6 absorption are all other B vitamins, vitamin C, magnesium, potassium, zinc, and high-quality protein.

Antidepressants, alcohol, coffee, exercise (to excess), estrogen therapy, and oral contraceptives appear to either increase the need for vitamin B6 or reduce its status. Diuretics and cortisone drugs block its absorption, and theophylline, an oral bronchodilator, antagonizes pyridoxal phosphate synthesis. (Ubbink et al., 1996)

VITAMIN B12, the most complex of the B vitamins, should be of special interest to vegans who, after chronic abstinence from animal products, can become seriously deplete in this nutrient. Most vitamin B12 deficiencies occur, however, not because of inadequate dietary consumption but rather because of poor absorption. It is important to note that neither man nor animal is able to synthesize or manufacture vitamin B12 in the body. Production of B12 is dependent upon simpler forms of plant life, such as fungi and bacteria. Animal derivatives, i.e., eggs, fish/marine life, beef/pork, and milk/dairy products are good sources of vitamin B12, but liver and kidney represent the very best sources.

Nutrients considered B12 enhancers are others of the B complex (especially folic acid and vitamin B6), vitamin C, iron, potassium, sodium, and calcium.

Medications to treat gout, anticoagulant drugs and potassium supplements may block the absorption of vitamin B12 from the digestive tract. For optimal B12 utilization, also, avoid coffee, alcohol, and laxatives. The intrinsic factor, a substance secreted by the gastric mucosa, is essential for the absorption of B12, transporting cyanacobalamin (vitamin B12) across the membranes of the ileum (the distal end of the small intestine).

FOLIC ACID rich foods are liver, kidney beans, lima beans, and fresh, green leafy vegetables (especially, spinach, asparagus, and broccoli). Other sources include most fish, beets, cabbage, eggs, whole grains, and citrus fruits. Fortification of enriched grain products with folic acid was associated with a substantial improvement in folate status in a population of middle aged and older adults. (Jacques et al., 1999)

Folic acid is most efficient when combined with vitamin B12, biotin, pantothenic acid, and vitamin C. According to the Committee on Dietary Allowances, heat and oxidation (occurring during cooking and storage) can destroy as much as half of the folate in foods.

Sulfa drugs interfere with the bacteria in the intestines that manufacture folic acid and Aminopterin and Streptomycin totally destroy folate. Methyltrexate (an anti-cancer drug) depletes folate, causing a transient elevation in homocysteine and phenytoin (an anti-epileptic drug) interferes with folate metabolism. Oral contraceptives, alcohol, coffee, and smoking are, also, considered folic acid antagonists.

MAGNESIUM
Reduces blood pressure, is a calcium antagonist and beta blocker, tempers sympathetic nervous system, beneficial in arrhythmias and mitral valve prolapse, increases the number and sensitivity of insulin receptors, has anti-diabetic properties, encourages the methylation process, prevents toxic buildup of homocysteine, reduces iron and calcium levels, is a vasodilator, opposes platelet aggregation

Magnesium, a potent vasodilator, may prove a better hypotensive, in some individuals, than calcium. Fifty-percent of magnesium-depleted patients are hypertensive, a condition often remediable with supplementation.

The Encyclopedia of Natural Medicine reported that magnesium supplementation lowered blood pressure by 12/8 mmHg in 19 of 20 subjects compared to 0/4 mmHg in a placebo group. (Murray et al., 1991) Magnesium reduces blood vessel contractibility by regulating levels of bradykinin, angiotensin II, prostaglandins, serotonin, epinephrine, norepinephrine, and dopamine; as a result, vessels vasodilate and blood pressure decreases.

Besides being a hypotensive mineral, magnesium is absolutely essential to proper cardiac function, allowing relaxation of the heart and supporting normal heart rhythms. In a study of patients admitted to coronary care units experiencing arrhythmias, 100% had complete resolution when administered intravenous magnesium over a 5-hour period. Dr. Bart Chernow, a surgeon at Sinai Hospital in Baltimore, reports that magnesium injections following bypass surgery reduced heart rhythm irregularities by 50%, without side effects. After 3 months of oral supplementation, platelet-dependent thrombosis, typically, is reduced by 35% in 75% of patients.

Calcium channel blockers are popular as anti-arrhythmics and antispasmodics. (To read more about calcium channel blockers, consult the section devoted to beta-blockers and calcium channel blockers, appearing in this protocol.) By relaxing arterial smooth muscles and reducing stress on the myocardium (the thick middle layer of the heart), magnesium yields, essentially, the same results as a calcium channel blocker.

Magnesium, also, replicates the activity of a beta-blocker, blocking the excitory nature of chemicals and lessening the "fight or flight" response of the sympathetic nervous system. Beneficial as magnesium is as a natural beta-blocker, beta-blockers should not be abruptly stopped and magnesium commenced; without a gradual withdrawal of the drug, a rebound could occur, provoking a heart attack.

Magnesium status is integral in both drug and nutrient therapies. If digitalis is administered in the absence of adequate levels of magnesium, a heart attack may result. Emphasizing potassium to correct a potassium deficiency, without adequate magnesium, may result in an erratic heartbeat, similar to that observed during digitalis dosing.

In mitral valve prolapse (MVP), the valve separating the left atrium from the left ventricle protrudes into the left atrium. Forty patients with MVP were investigated and low magnesium levels were a significant finding, suggesting it plays an important role in the disturbance. Numerous studies indicate that magnesium lessens MVP symptoms, i.e., non-anginal chest pains, palpitations, fatigue, and breathing difficulties. Note: Low magnesium levels, also, are correlated with angina attacks in men. It appears as magnesium status drops, the frequency of angina attacks increase. (Satake et al., 1996)

Too much calcium in the bloodstream may be a forerunner to aortic stenosis, i.e., a narrowing of the valve between the left ventricle and the aorta. Magnesium hinders the absorption of calcium; therefore supplementing with at least 500 mg/day could inhibit excesses of calcium hardening the cusps of valves. For a comprehensive look at aortic stenosis, consult the section of this protocol dedicated to valvular disease. Note: Magnesium oxide, also, appears to reduce excesses of iron accumulating in the body. The dangers of hemochromatosis are discussed in the section entitled Traditional Risk Factors.

Magnesium plays an important role in the prevention and treatment of Syndrome X and diabetes. It benefits these conditions by increasing the production and release of insulin and increasing the number and sensitivity of insulin receptors.

Magnesium, by encouraging the methylation process, reduces toxic buildup of homocysteine. As long as disposal pathways for homocysteine clearance are functional, homocysteine does not promote atherosclerosis.

Unfortunately, the test used by the majority of physicians to measure magnesium levels is worse than useless, according to Dr. Sherry A. Rogers, an environmental medicine specialist. Dr. Rogers refers to this test as "the most dangerous test in medicine" for if it is used, it too often shows misleading normal levels. The assumption that adequate amounts of magnesium exists when, in fact, deficiency states exist, may be a fatal mistake. The Journal of the American Medical Association published a study reporting that about 90% of practicing physicians never think to check magnesium levels, even in patients who are severely depleted. (Whang et al., 1990) Note: Magnesium deficiency is better detected by measuring mononuclear blood cell magnesium, as opposed to serum levels.

Dosage suggestions: 500 to 1500 mg daily of magnesium bound to succinate, citrate, or aspartate. Magnesium oxide, in larger doses, can cause a loose stool.

READERS GUIDE TO MAGNESIUM-RICH FOODS, ENHANCERS and ANTAGONISTS: Magnesium is found in many foods but particularly in nuts, grains, legumes, dark-green vegetables, and most fish. Good sources per kcal are spinach, broccoli, tomato juice, navy and pinto beans, sunflower seeds, tofu, halibut, cashews, artichoke and black-eyed peas. (Whitney et al., 1998)

Magnesium enhancers include the B-complex (especially vitamin B6), vitamin C, calcium, essential fatty acids and amino acids. The body's requirement for magnesium increases if using alcohol, taking higher levels of zinc and vitamin D, or exposed to fluoride, unrelenting stress, or tobacco. Dietary fats and fat-soluble vitamins, cod liver oil, calcium (large amounts), iron, and excesses of protein decrease magnesium absorption. Oxalic acid foods, as rhubarb, spinach, tea, almonds, chard, and cocoa, also, hinder its absorption. Diuretics and chronic diarrhea can seriously deplete many minerals, including magnesium.

NIACIN (Vitamin B3)
Lowers Lp(a), reduces fibrinogen, normalizes blood lipids, acts as a vasodilator

Nicotinic acid and nicotinamide are types of the vitamin niacin; though related, they are different in their therapeutic delivery. Clin Rev Spring reported that though nicotinamide is often marketed as a superior lipid-lowering version of niacin, it actually has little effect in lowering lipids. (Segrest, 2000) It is nicotinic acid that modulates most all lipid parameters, i.e., lowering total cholesterol levels, LDL, VLDL, Lp(a), and triglycerides, while increasing HDL cholesterol. Nicotinic acid has, in fact, won favor with the FDA, adding it to a list of other remedials capable of lowering triglycerides.

Because of niacin's broad-spectrum effectiveness against hyperlipidemia, niacin can act independently or in concert with other drugs. Dr. B. Greg Brown, of the University of Washington (Seattle) reported to the American Heart Association that a combination of a statin drug (which lowers LDL cholesterol) and niacin (which raises HDL cholesterol) brought the progression of atherosclerotic disease to a standstill. Simvastatin (Zocor) plus niacin increased HDL levels 30% over baseline, while Zocor alone increased HDL only 7% to 10%. Jere P. Segrest, M.D., Ph.D., states that nicotinic acid can act independently, accomplishing what no drug can currently do, i.e., lowering lipoprotein(a). Niacin, typically, reduces Lp(a) levels by about 35%.

Niacin has properties that are the opposite of those of nicotine. Nicotine, a toxic substance in tobacco, is a vasoconstrictor (narrows blood vessels); niacin is a vasodilator, i.e., it widens blood vessels. Niacin's vasodilating quality makes it beneficial in the treatment of hypertension and various forms of heart disease.

Researchers at Auburn University found that small amounts of niacin in combination with chromium lowered cholesterol levels by an average of 14%. This finding is valuable, since niacin has some significant side effects, making it less justifiable in large doses. Articles appearing in the American Journal of Cardiology and in the Journal Cardiovascular Risk confirmed niacin's hypolipidemic value and, also, reported that low-dose niacin was effective in reducing plasma fibrinogen levels in subjects with peripheral vascular disease. (Philipp et al., 1998) (Ma et al., 1999)

If used independently, 1 to 3 grams of niacin is, sometimes, required to lower cholesterol levels, a dosage that can cause side effects ranging from nuisance complaints to significant endangerments. Allergic-like reactions i.e., itching and flushing, are common, but niacin can, also, disrupt liver function causing elevations of liver enzymes. (Sustained-release niacin preparations are regarded as more hepatotoxic, GI tract disturbing, and less effective in raising HDL levels than regular or crystalline forms.)

Other risks associated with niacin:

	Fasting serum glucose increases in about 30% or more of patients treated with high-dose niacin. This occurrence is most observed in those insulin resistant and with a predisposition for type 2-diabetes.
	Individuals who are insulin resistant can experience an increase in uric acid while dosing with niacin, a rise that can bring on a gout attack.
	In a recent study, nicotinic acid (1 gram per day) raised homocysteine levels 1.5 mg/dL.
	Niacin can deplete S-adenosylmethionine (SAMe). The lack of sufficient detoxification (due to SAMe depletion) explains many of the adverse effects associated with niacin dosing.

Considering these negatives, large dose niacin may be too great a price to pay for the benefits. If a decision is made to use high-dose niacin, some practitioners report that an aspirin taken 30 minutes before the dose, markedly, reduces some of the lesser side effects, i.e., the allergic-like symptoms.

READERS GUIDE TO VITAMIN B3 SOURCES, ENHANCERS, AND ANTAGONISTS: The richest sources of niacin are organ meats, brewer's yeast, and peanuts. Lean meats, poultry, and fish are, also, reliable sources. Milk and eggs contain smaller amounts of niacin, but represent excellent sources of tryptophan (the precursor to niacin). In addition, the niacin yield per kcal is good in the following foods: spinach, tomato juice, shrimp, chicken breast, lean ham, tuna, and mushrooms.

Vitamin B3 enhancers (in regard to absorption) are the B-complex (especially B1, B2, and B6), vitamin C, magnesium, zinc, protein, and essential fatty acids. Antagonists to niacin absorption are alcohol, coffee, excess sugar, antibiotics, and steroids.

OLIVE LEAF EXTRACT
Hypotensive, anti-diabetic, vasodilating, helpful in some types of arrhythmias, protective against LDL oxidation

Olive leaf extract (Olea europaea) though historically regarded as a medicinal for fever and malaria, is, also, valuable in the treatment of cardiovascular disease. Olive leaf extract has been shown, in both laboratory and clinical settings, to have anti-diabetic, hypotensive, and vasodilating properties. Researchers documented that an aqueous extract of olive leaves inhibits the angiotensin converting enzyme (ACE), the enzyme that converts angiotensin I to angiotensin II. The vasoconstricting nature of angiotensin II terminates in an increase in blood pressure, a sequence that olive leaf extract disrupts. It is estimated that oleuropein, one of the medicinal properties of olive leaf, reduces blood pressure by about 25%.

European scientists confirmed that olive leaf extract increases blood flow to coronary arteries and relieves arrhythmias. Chelation therapy, in conjunction with an aggressive supplemental program that relied heavily upon olive leaf extract, has proved remedial among select senior subjects who have suffered multiple heart attacks and arrhythmias. In addition, olive leaf protects LDL cholesterol against oxidation and inhibits the production of thromboxane A2, a compound that stimulates platelet aggregation and vasoconstriction. Suggested dosage: One to two 500-mg olive leaf extract capsules, administered three times daily with meals.

PANTETHINE
Reduces cholesterol, discourages platelet clumping, and has antioxidant activity

Pantethine, a biologically active, intermediate form of pantothenic acid (vitamin B5) and a precursor to co-enzyme A, is a powerful natural pharmaceutical that reduces cholesterol, increases heart muscle contractility, slows the heart rate, and has antioxidant activity.

Patients (24) with irregularities occurring in either total cholesterol or subsets of cholesterol received 300 mg of pantethine 3 times per day. Clin Ther reported that pantethine reduced mean serum cholesterol levels up to 17%, triglycerides by 48%, and increased HDL cholesterol by 15% after 1 year's usage. (Aresenio et al., 1986) A decrease in thromboxane A2 and the resultant platelet clumping was observed during pantethine supplementation. Other studies showed that discontinuing pantethine and switching to a placebo prompted a rapid return to baseline lipid levels. Dosage suggestions: 300 mg three times a day.

PHTHALIDE
Lowers blood pressure

A study conducted at the University of Chicago Medical Center showed that a natural compound, 3-n-butyl-phthalide found in carrots, celery, cilantro, parsley, and parsnips, have a dramatic effect upon hypertension. In fact, after just seven days, phthalide dropped blood pressure by about 30%. One cannot be delicate about consuming these vegetables, however, for it takes about ¼ of a pound/day to reduce blood pressure.

Phthalide influences blood pressure by relaxing arterial muscles, dilating blood vessels, and inhibiting stress hormones.

POLICOSANOL
Hypocholesterolemic, protects LDL cholesterol against oxidation, inhibits thromboxane and proliferation of vascular cells, discourages blood clot formation, has anti-platelet aggregating activity, increases exercise tolerance

Policosanol, derived from sugar cane, is a new face on the cholesterol scene in the U.S., but a popular hypocholesterolemic in other countries. The main ingredient in sugar cane is octacosnol, a long-chain fatty alcohol found in the waxy film that covers the leaves and fruit of plants.

Policosanol represents an effective alternative to lowering cholesterol. For example, 10 mg/day of policosanol (over a 6 to 12 week period) lowered LDL cholesterol 20%, total cholesterol by 15%, and raised the beneficial HDL cholesterol by 7% to 28%. Doubling the dose (20 mg/day) resulted in the following lipid improvements: LDL cholesterol reduced about 28%, total cholesterol about 20%, and HDL increased by 7% to10%. Triglycerides were unaffected. During the course of the trial, participants continued on a low-cholesterol diet.

Policosanol's hypolipidemic effects are comparable to many cholesterol-lowering drugs. Rev Med Chile published the results of a head to head study classing drug therapy against policosanol. (Prat et al., 1999) See Figure 6:

Policosanol, also, outclassed the drugs, in regard to increasing levels of the beneficial HDL cholesterol. Yet, a combination of policosanol and gemfibrozil (Lopid) was a more effective hypocholesterolemic than either used singularly. In fact, policosanol even upgraded the efficiency of bezafibrate, a once touted fibrinogen-lowering drug that yielded disappointing results in The Bezafibrate Infarction Prevention Study. (Behar, 1999) Bezafibrate in union with policosanol dramatically reduced LDL and total cholesterol. In addition, policosanol appears to replicate another of the objectives of statin drugs, i.e., reducing the proliferation of cells. (A telltale sign of a diseased vessel is that the smooth lining of the vessel becomes thickened and overgrown with cells.)

When comparing the value of a drug to a natural alternative, safety factors must be considered. Usually, the protractions off of a nutrient, in contrast to a drug, are not side effects but side benefits. For example, the oxidation of LDL cholesterol (a particularly destructive form of cholesterol that creates chronic inflammation) is inhibited by policosanol. As less inflammation and blood vessel destruction occur, fewer foam cells appear. Conversely, if the oxidation of LDL is not inhibited, metalloproteinase enzymes are aroused, further damaging the vasculature by interfering with the protective nature of HDL cholesterol.

Policosanol combines well with aspirin to inhibit the formation of clots, with each influencing the activity of different platelets. This synergistic approach provides more comprehensive protection against platelet aggregation. Another factor in blood clot formation, thromboxane (a blood vessel constricting hormone-like chemical) is repressed after a couple of weeks of policosanol therapy.

Policosanol users can expect an improvement in exercise tolerance. When patients with heart disease were given 10-mg/day of policosanol, exercise capacity and oxygen uptake increased but ischemia (a deficiency of blood due to functional constriction or actual obstruction of a blood vessel) decreased. Improvement in treadmill-ECG tests confirmed that policosanol benefits heart patients, but healthy, physically active individuals, also, reported increases in exercise tolerance and strength.

Policosanol does not appear to interfere with other heart medications. It may, however, potentiate the effects of propranolol, a beta-blocker used to treat hypertension. The 10 mg dose has had more than 2 years clinical testing with no significant ill effects reported, except in some patients an unexpected weight loss occurred. Note: policosanol has undergone as many clinical trials as most drugs. Suggested dosage: Some individuals will need only 5 to 10 mg to maintain healthy levels of cholesterol; others will require 20 mg a day.

POLYENYLPHOSPHATIDYLCHOLINE (PPC)
Hypolipidemic, improves exercise tolerance, lessens angina attacks

Phosphatidylcholine, the main component of lecithin (a soy product) has a long history as a preventive in arteriosclerosis, cardiovascular disease, and brain derangements. Polyenylphosphatidylcholine (PPC), a newer, polyunsaturated soy derivative, has shown extraordinary promise in managing hypercholesterolemia. It appears that PPC delivers its value by traversing into cholesterol, where direct modulation of the substance occurs. PPC, also, decreased postprandial triglycerides, LDL, and apoB, a protein component found in low-density lipoprotein (LDL), very low-density lipoprotein (VLDL), and intermediate-density lipoprotein (IDL) cholesterol.

Russian researchers compare PPC to niacin in the treatment of angina and hyperlipidemia. While nicotinic acid is a reliable hypocholesterolemic, clusters of annoying symptoms (flushing and itching) and less benign side effects (liver disruption and GI disturbance) discredit mega-dose usage in some individuals. Conversely, PPC therapy has no contraindications, side effects, or drug interactions.

PPC has a positive effect upon HDL levels, particularly the most protective of the HDL family HDL2b. Individuals attaining longevity often display HDL differentials favoring HDL2b, suggesting this subfraction renders, among other health benefits, greater cardioprotection. Another of the restorative capacities of PPC are reports of increased exercise tolerance.

Alcohol, in moderation, appears to prevent atherosclerosis. Heavy drinking has the opposite effect, in part, by promoting oxidation of LDL cholesterol. Administering PPC at 2.8 g/1000 kcal to baboons made alcoholic for experimentation lessened the expected ethanol-induced increase in LDL oxidation. Suggested dosage: two 900-mg capsules daily.

POTASSIUM
Reduces blood pressure, maintains fluid balance, encourages parasympathetic nervous system, increases insulin sensitivity

Potassium, considered by some the major electrolyte, is found almost exclusively in the intracellular fluids of the cell. Sodium is found in the extracellular fluids, but it is equilibrium between potassium and sodium that determines fluid balance and blood pressure regulation. A high potassium-low sodium intake reduces the blood vessel constricting effects of adrenaline, a hormone elicited by the sympathetic nervous system; lower blood pressure results.

Thirty-seven adults, with mildly elevated blood pressure, participated in a study to determine the hypotensive nature of minerals. Potassium (2.5 gram/day), administered for 8 weeks, reduced systolic pressure by an average of 12 mmHg and diastolic blood pressure by about 16 mmHg. The addition of magnesium offered no further advantage. (Patki et al., 1990) The major benefit of potassium, typically, occurs during the third month of usage and continues thereafter.

Hypertensive individuals over 65 years of age may find particular value in potassium, since medications are not always as effective among senior subjects. Administering 2.5 grams/day of potassium over 4 weeks to 18 untreated elderly hypertensive patients resulted in a systolic drop of 12 mmHg and a diastolic reduction of 7 mmHg. (Fotherby, 1992) All entered the study with systolic blood pressure >160 mmHg and diastolic pressure >95 mmHg. The results were impressive considering the brevity of the study and the fact that potassium's value is cumulative, meaning a greater response is seen with longer supplementation.

The hypotensive nature of potassium benefited a group of rats made stroke prone for experimentation. The rats were divided into two groups. Only 2% of the potassium-supplemented group suffered a fatal stroke, compared to 83% of the untreated group. (Staff of Alternative Medical News, 1995)

Most physicians are aware of the importance of reestablishing potassium levels after administering a diuretic drug for hypertension or congestive heart failure. Patients are commonly told to replace potassium by consuming potassium-rich foods, even though retention of potassium from foodstuffs is poor. The New England Journal of Medicine reported that if every milligram of potassium in a banana were retained, it would require eating an entire stock of bananas every day to offset the potassium lost during diuretic therapy. (Cuneo et al., 1985)

Several factors influence potassium levels. For example, insulin therapy appears to cause a potassium deficiency. (Conversely, a diabetic supplementing with potassium may observe increased insulin secretions and responsiveness, reducing insulin requirements.) Physical exertion (producing heavy perspiration) or diarrhea and vomiting (resulting in loss of body fluids) can cause a mineral depletion. Always replace minerals, for if not replaced, heart function can quickly depreciate. Symptoms of potassium deficiency are weakness, fatigue, mental confusion, and heart disturbances.

Suggested dosage: potassium intake should be between 1.9 grams and 5.6 grams/day. If diet does not provide adequate amounts of potassium (widely available in fruits and vegetables), supplementation becomes essential. Individuals taking digitalis, potassium-sparing diuretics, and the angiotensin-converting enzyme inhibitor should not "self dose" without consultation with a physician.

READERS GUIDE TO POTASSIUM FOOD SOURCES, ENHANCERS, AND ANTAGONISTS: Fruits, as apricots, bananas, dates, oranges, figs, strawberries, and raisins are excellent sources of potassium. Most vegetables (acorn squash, artichoke, potato skins, yams, spinach, broccoli, carrots, green beans, and tomatoes) also provide potassium. Other sources include dairy products, meat, cereals, and legumes.

Potassium enhancers (regarding absorption) are vitamin B6, calcium, magnesium, and essential fatty acids. Antagonists to potassium include excesses of sodium, sugar, stress, alcohol, and coffee, plus steroids, diuretics, and laxatives.

PROANTHOCYANIDINS
Antioxidant, reduces platelet aggregation, protects endothelium against white blood cell adherence, increases exercise tolerance, beneficial to smokers, is a weak ACE inhibitor

Many names, aptly, describe the flavonoids found in pine bark, grape seed, citrus peel, lemon tree bark, peanuts, and cranberries. The scientific community once referred to this entire family as pycnogenols, a term now considered outdated. Today pycnogenols are recognized by terms, such as proanthocyanidins, oligomeric proanthocyanidin complexes (OPCs) or procyanidolic oligomers (PCOs). In the United States, Pycnogenol is a registered trademark for Horphag Ltd. of Switzerland, identifying a PCO derived from French maritime pine trees.

Much discussion as to whether pine bark or grape seed extract delivers the most medicinal advantage, still leaves the question unresolved. Dr. Michael Murray states that while both are excellent sources of proanthocyanidins, grape seed extracts are available that contain from 92% to 95% PCO content; pine bark extracts vary from 80% to 85%. Dr. Murray adds that an overwhelming majority of the published clinical and experimental trials over the past 20 years have been performed using the grape seed extract, not the extract of pine bark.

Reports from the Institute of Pharmaceutical Chemistry (Germany) indicate that PCOs lower platelet aggregation in heavy smokers without increasing the risk of bleeding. Smokers were given oral doses (200 mg/day) of pine bark extract for 8 weeks. Tests confirmed that the platelet aggregation index was reduced to levels closely challenging those found in non-smokers, in part, by inhibiting the synthesis of thromboxane, a compound derived from inflammatory prostaglandins that increases platelet aggregation.

PCOs are diverse, considering defensive mechanisms that influence the heart's performance. For example:

	Pycnogenol exhibits a weak inhibition of ACE (the Angiotensin-Converting Enzyme). This means that the production of angiotensin II (a vasoconstricting compound) is blocked and sodium and water retention decreases. These actions decrease blood pressure and improve cardiac output; a decrease in heart size usually follows.
	PCOs protect the endothelium from leukocyte adherence, a process that lessens the threat of occlusion.
	PCOs increase intracellular vitamin C levels, a function that strengthens capillary and blood vessel walls.
	PCOs appear to offer about 50 times more antioxidant protection than vitamin C or vitamin E, an action that assists in shielding LDL cholesterol from the cardiac damaging oxidation process.
	PCO extracts have been shown to lower blood cholesterol levels, even shrinking the size of cholesterol deposits appearing in the arteries of laboratory animals.
	Electrocardiograms and stress tests confirm the benefits of PCO. PCO treated patients had less myocardial ischemia, cardiovascular deterioration, and increased treadmill endurance compared to non-treated patients.

Peter Rohdewald, Ph.D., reported that nitric oxide (NO) became the molecule of the year in 1993 when, among other functions, it was determined that NO was a powerful vasodilator. NO is produced in the endothelial cells from arginine, a process controlled by the enzyme endothelial nitric oxide synthase. Scientists became additionally excited when it was determined that PCOs stimulate endothelial nitric oxide synthase, producing more nitric oxide. This action counteracts the vasoconstricting effects of the stress hormone adrenaline and also diminishes the threat of platelets clumping.

Studies indicate that PCO may be an alternative to aspirin. Among 180 post stroke patients receiving 500 mg/day of aspirin for 2 years, 21% were forced to stop medication because of side effects and a > 41% increase in bleeding time. John D. Folts (University of Wisconsin) reported that encapsulated flavonoids benefited laboratory monkeys, reducing the incidence of platelet aggregation and blocked arteries with efficiency equal to or greater than aspirin. Adrenaline, a stress hormone released from the adrenal medulla, can completely wipe out the positive effects of aspirin, but adrenaline (epinephrine) has no degrading effect on flavonoids. PCOs offer neither GI toxicity nor an effect on coagulation, suggesting a better risk/benefit ratio compared to aspirin (Watson, 1999)

Research cited in the Lancet showed an inverse relationship between flavonoid intake and the risk of heart attack, i.e., the more flavonoids ingested, the less the incidence of heart disease. (Hering et al., 1993) PCOs provide some of the most beneficial classes of plant flavonoids available.

Suggested PCO dosage: for most individuals 50-100 mg daily appears adequate. Therapeutic doses are 150-300 mg/day. Note: While proanthocyanidins do not prolong bleeding time when used independently, if used with anticoagulant drugs, caution is advised.

RED YEAST
A hypolipidemic

Red yeast, a by-product of rice fermentation, has become popular among users of natural medicine as a hypolipidemic. It is possible that the hype pertaining to red yeast's ability to lower cholesterol levels has masked red yeasts true character. Historically, red yeast has been used in China for 2000 years to make rice wine and to improve digestion. In 1977, Professor Akira Endo (Japan) discovered that a strain of the yeast produces substances that block metabolic pathways responsible for cholesterol production.

Its therapeutic value as a hypolipidemic is due to monacolin K, an inhibitor of HMG-CoA reductase. (Walker, 1997) Inhibition of HMG-CoA reductase, a rate- limiting enzyme, disrupts the cycle that terminates in the endogenous production of cholesterol. The blocking of cholesterol biosyntheses by red yeast (monacolin K) stimulates hepatocytes to form greater numbers of LDL receptors. This, according to Varro Tyler, Professor Emeritus Purdue University, promotes an increased influx of LDL cholesterol from the plasma to participate in bile acid synthesis, with a resulting decrease in plasma LDL cholesterol levels. Cumulative results from various studies indicate red rice yeast, typically, lowers total cholesterol levels by about 18% and LDL levels by about 23%.

The user may not be aware that the major active constituent of red yeast, monacolin K, is the popular hypocholesterolemic prescription drug, lovastatin. Red yeast and lovastatin deliver the same hypolipidemic value but also, the same side effects, i.e., the possibility of gastritis, abdominal discomfort, elevated levels of liver enzymes, muscle pain, tenderness, and weakness. Red yeast is not appropriate for users with either established or suspected liver disease or pregnant women. (Cholesterol plays a major role in fetal development.) If red rice becomes the hypolipidemic of choice, the suggested dosage is 4 capsules daily (each capsule containing 600 mg).

SELENIUM
Prevents ventricular tachycardia, is a hypolipidemic, improves diabetic symptoms, congestive heart failure, and cardiomyopathy

Cardiomyopathy is defined as any disease that affects the structure and function of the heart. For example, the heart may become disabled as fibrous tissue partially replaces the heart muscle; the fibrous tissue, degrades the heart's performance and the blood no longer moves efficiently. The World Health Organization recognizes cardiomyopathy as a selenium deficiency. Selenium supplementation appears valuable in the treatment of cardiomyopathy, often sparing the patient grave illness and surgery. A selenium deficiency, often, accompanies congestive heart failure, as well.

P.V. Luoma, researcher, noted that 97 mcg of selenium per day increased the ratio of HDL to LDL cholesterol, while inhibiting platelet aggregation. It is purported that a 1% increase in HDL reduces the risk of a heart attack or stroke by 4%.

Selenium limits the incidence of ventricular tachycardia, i.e., 3 consecutive ventricle complexes, with the heart rate more than 100 beats per minute, from 91% in the control group to 36% in the selenium treated group.

H. Korpela, in a 6-month double-blind trial involving 81 heart attack patients, found that 100 mcg of selenium reduced the number of cardiovascular events to one nonfatal heart attack, while the group not receiving the selenium suffered four fatal heart attacks and two nonfatal heart attacks. (Korpela et al., 1989)

Selenium brought blood glucose levels, malondialdhyde (a breakdown product of peroxidized polyunsaturated lipids), and glutathione concentrations to near control values in almost all diabetic patients. Suggested dosage: 200-300 mcg daily.

READERS GUIDE TO SELENIUM FOOD SOURCES, ENHANCERS, AND ANTAGONISTS: Selenium values are dependent upon the soil content from which the foodstuff was harvested. But, whole grains, milk products, meat, seafood, wheat germ, broccoli, onions, tomatoes, Brazil nuts, brewer's yeast, garlic, salmon, tuna, and eggs are classed as selenium sources.

Selenium enhancers include most antioxidants and essential fatty acids. Antagonists to selenium absorption are heavy metals (mercury and cadmium), excesses of iron, saturated and trans fats, unresolved stress, and indulgences in alcohol and tobacco.

SOY PROTEIN
Reduces cholesterol and enhances thyroid function (an integral gland in the heart's performance)

Historically, cultures using dietary soy have better cholesterol levels and less heart disease. Some researchers consider the representation of amino acids in soy the factor that most affects cholesterol dynamics. Yet, saponins, a soapy material found in soy, along with fiber, protease inhibitors, isoflavones, tocotrienols, lectins, and select vitamins/minerals are, also, considered hypocholesterolemic. The synergism of many phytonutrients appears to be blocking the absorption of cholesterol, increasing the conversion of cholesterol to bile salts, and degrading the activity of HMG-CoA reductase.

Diets based on animal protein raise cholesterol and lower thyroxine levels compared to a plant-based diet. The hypocholesterolemic effect of soy includes increasing concentrations of thyroxine (a hormone secreted by the thyroid gland) when added to an animal protein diet. An increase in thyroxine, typically, precedes a decrease in cholesterol.

Clinicians examining a group of heart attack victims, younger than 40 years of age, found two common abnormalities: (1) elevations in serum cholesterol and (2) reductions in basal metabolic rate (symptoms common to hypothyroidism). Confirmation of the fact that an increase in plasma thyroxine concentrations precedes reductions in plasma cholesterol illustrates the importance of a healthy response from the thyroid gland. Attempts to reduce cholesterol levels without factoring in the possibility of a poorly functioning thyroid gland diminish the chance of success. Conversely, remarkable improvement in blood lipids can be expected if hypothyroidism exists and is treated as the primary condition provoking the hypercholesterolemia. It may be life saving for the patient to recommend a thyroid evaluation if it is not suggested by the physician.

The New England Journal of Medicine published a summary of 38 studies involving 730 people, and found that eating an average of 47 g of soybeans per day reduced total cholesterol levels by 9.3%, LDL by 12.9%, and triglycerides by 10.5%. HDL levels were unchanged. (Anderson, et al., 1995)

Nurturing the thyroid gland is always "good medicine." This can be accomplished through dietary and supplemental selections (if the condition is mild) or by administering thyroid extract. Suggested soy dosage: 47 gm (slightly less than 4 tablespoons daily). To read more about the role of the thyroid gland in heart disease, consult Hypothyroidism in the section describing traditional risk factors.

TAURINE
Has hypotensive and diuretic activity, tempers sympathetic nervous system, beneficial in congestive heart failure and arrhythmias, has digitalis-like mentality

Taurine is the most important and abundant of the amino acids in the heart, surpassing the combined quantity of all the others. Under high stress conditions, i.e., hypertension and many forms of heart disease, the need for taurine increases to compensate for either an accompanying impairment of taurine metabolism or increased requirements. Dr. H. Kohaski and colleagues (Japanese researchers) suggest that entry-level taurine may have been low and, as the stress of hypertension progresses, taurine levels drop even lower.

Taurine has a diuretic action that benefits hypertensive individuals, as well as patients with congestive heart failure. Taurine elicits much of its diuretic action by preserving potassium and magnesium and by promoting sodium excretion.

Taurine, also, reduces blood pressure, by acting as an antagonist to the blood pressure-increasing effect of angiotensin, a circulating protein that is activated by renin, a hormone secreted by the juxtaglomerular cells of the kidneys in response to a drop in blood pressure. When both blood and urine taurine levels decrease, renin is activated and angiotensin is formed. As a result blood vessels vasoconstrict, water and salt are retained, and blood pressure increases. Taurine suppresses renin and breaks the renin-angiotensin feedback loop. Dr. Robert Atkins, a complementary physician with a creditable cardiology background, amplifies the positive results of the scientific literature, stating that taurine would be his choice were he selecting a single nutrient to treat hypertension.

Dr. Y. Yamori (a Japanese researcher who established an amino acid/stroke association) studied a strain of rats, genetically susceptible to strokes. Yamori found the rats had a much lower incidence of stroke, dropping from 90% to 20%, if their diet was supplemented with methionine, taurine and lysine.

A study in the Japanese Circulation Journal reported that 3 gm of taurine, administered daily to patients suffering from congestive heart failure, was more effective than 30 mg of CoQ10. (Azuma et al., 1992) The Japanese, who widely use taurine in the treatment of various forms of heart disease, found that 4 gm of taurine, given for four weeks, brought relief to 19 out of 24 patients with congestive heart failure. Taurine appears to act much like the drug digitalis, increasing the contractility of cardiac muscle and the force of the pumping action.

Some forms of cardiac irregularities are helped by taurine because it regulates membrane excitability. Taurine protects potassium levels inside heart cells, which, when imbalanced, can cause electrical instability and cardiac arrhythmias. Normalization of the sympathetic nervous system, i.e., regulating the outpouring of epinephrine and the production of beta-endorphins (natural opiates) are cardiac regulating functions of taurine. (Reports indicate, however, that taurine should not be relied upon to treat ventricular tachycardia.) Dosage suggestions: 1500 to 4000 mg daily.

TESTOSTERONE…Drugs and Natural Sources
Modulates cholesterol levels, dilates blood vessels, improves circulation, lessens angina attacks, reduces blood pressure

Testosterone, a muscle-building hormone, appears to do far more than promote the development of male secondary sexual characteristics. There are, in fact, many testosterone-receptor sites in the heart that play a role in maintaining heart muscle protein synthesis and strength. (Bricout et al., 1994)

If testosterone levels are adequate, cholesterol is more easily managed and blood has an easier route as it flows through dilated vessels. One study showed that circulation to the heart improved by 68.8% in those receiving testosterone therapy. (Wu et al., 1993) A testosterone delivery patch applied to men with low testosterone increased exercise time on a treadmill by 37% (control group 15%) due to greater dilation of blood vessels. Improved emotional health (important to the heart) and a decrease in the incidence of angina attacks reflect the benefits of upgrading testosterone levels. (English et al., 2000)

Typically, fibrinogen, triglycerides, and insulin levels are higher if testosterone levels are low. (Marin, 1995) The elasticity of the coronary arteries diminishes, contributing to the development of arteriosclerosis. Blood pressure increases, but the growth hormone decreases, further weakening the heart muscle. Abominal fat, the most dangerous form of obesity, increases.

Physicians who check for testosterone deficiencies or testosterone/estrogen imbalances have, in some cases, been able to discontinue cardiac and hypertension medications. Improved EKGs confirm subjective reports of improvement. Since testosterone testing is noninvasive, the risk/benefit ratio swings heavily in favor of testing. Note: There are no safe limits for hormone imbalances, considering physical and emotional health. For information about safely increasing testosterone levels, refer to the Male Hormone Modulation Protocol (or Female Hormone Modulation Protocol).

THIAMINE (VITAMIN B)
Beneficial in some forms of cardiac arrhythmias, palpitations, enlarged heart, elevated venous pressure, and congestive heart disease

Cardiac arrhythmia refers to a deviation from the normal pattern of the heartbeat. Arrhythmias can be caused by a variety of underlying medical conditions that should be addressed by a qualified cardiologist. Arrhythmias are not always clinically significant, for rather benign events can spur healthy hearts to enter irregular patterns of beating. Yet, arrhythmias should be taken seriously and a diagnosis made as to the causative factors provoking the deranged beat. Stress, electrolyte imbalance, ischemia, hypoxia, ventricular enlargement, occlusions, an insulin rush, or derangement in the autonomic nervous system can drive a heart into irregular rhythms.

Since thiamine has proved correctional for some types of arrhythmias, there may be linkage between irregular heartbeats and beriberi, a disease caused by a deficiency of or an inability to assimilate thiamine. Cultures that depended upon rice, a high-carbohydrate food, as a dietary mainstay found the milling process, i.e., the removal of the brown coat rich in thiamine, their undoing. Beriberi swept through the population with epidemic force.

A thiamine-deficient individual cannot digest carbohydrates efficiently; and as the dog chasing his tail, a high carbohydrate diet depletes thiamine. Excessive carbohydrates invite an insulin rush, a hallmark of Syndrome X. Excesses of insulin can act as an excitory, goading the heart into irregular rhythms. Administering vitamin B1, in union with a low carbohydrate diet, may reestablish normal heart rhythms in individual's carbohydrate sensitive.

Thiamine deficiencies can, also, cause palpitations, rapid rhythm, enlarged heart, elevated venous pressure, myocardial lesions, and congestive heart failure. In 1995, 30 patients with severe heart failure and taking furosemide (Lasix, a diuretic) were enrolled in a study. Though the furosemide was unsuccessful in improving their cardiac condition, 200 mg of thiamine (per day) dramatically improved heart function. (Shimon et al., 1995)

Suggested thiamine dosage: some patients may experience improvement from 200 to 250 mg per day; other individuals may require 500-1000 mg daily. (Single B vitamin supplementation should be accompanied by a full-spectrum vitamin B complex.)

READERS GUIDE TO VITAMIN B1 FOOD SOURCES, ENHANCERS, AND ANTAGONISTS: Lean pork, wheat germ, and grains are considered excellent sources of thiamine. All organ meat (especially liver), lean meats, poultry, egg yolk, fish, dry beans, peas, soybeans, peanuts, sunflower seeds, brewer's yeast, and brown rice represent other good thiamine choices.

Vitamin B1 enhancers are all others of the B complex, vitamin C, vitamin E, and manganese. Alcohol, coffee, tea, antacids, and excesses of sugar and refined carbohydrates decrease thiamine absorption. Antibiotics, sulfa drugs, and oral contraceptives are, also, regarded as thiamine antagonists.

TOCOTRIENOLS
Antioxidant, decreases platelet aggregation, has "statin" mentality

Tocotrienols have been, until recently, the lesser-known half of vitamin E. The major functional difference between tocotrienols and tocopherols appears to be the ability of tocotrienols to more aptly decrease cholesterol synthesis in the liver. Free Rad. Biol. Med. reported that both tocotrienols and tocopherols appear to be potent antioxidants, with some research demonstrating higher antioxidant activity and less oxidative damage when supplementing with tocotrienols. (Serbinovat, et al., 1991)

Cholesterol lowering drugs, referred to as statin drugs, i.e., Lipitor, Lescol, Mevacor, Pravachol and Zocor, operate at the level of 3 hydroxy-3 methylglutaryl coenzyme A (HMG-CoA) reductase. HMG-CoA reductase is a rate-limiting enzyme that participates in cholesterol synthesis. The cholesterol cascade occurs as follows: (1) the conversion of acetyl CoA to HMG-CoA, (2) HMG-CoA is reduced to mevalonic acid by the enzyme HMG-CoA reductase, (3) several steps convert mevalonic acid to squalene, and then to cholesterol.

A study published in J Biol. Chem. indicates that tocotrienols accelerate the degradation of the enzyme HMG-CoA reductase, altering the functionality of the enzyme responsible for cholesterol synthesis. (Parker, et al, 1993) Of the family of tocotrienols, gamma and delta, appear particularly effective in cholesterol control.

The statin drugs, though acting at the level of HMG-CoA reductase, approach the enzyme differently. Statin drugs do not degrade the enzyme but competitively inhibit its binding. Inhibition of the binding mechanism leads to a higher production of HMG-CoA reductase, which may explain the side effects, as liver toxicity, associated with statin usage.

Nutr. Biochem reported that after 4 weeks of tocotrienol supplementation, total cholesterol levels dropped up to 16% in 75% of patients. (Qureshi et al., 1997) Other studies showed a 21% reduction in LDL cholesterol. HDL levels do not appear to respond to tocotrienol supplementation, but apolipoprotein-B, a protein component found in LDL, VLDL, and IDL cholesterol is lowered. Platelet aggregation decreased by 15%.

Lipids reported that in 23 of 25 patients with carotid atherosclerosis, the disease was either halted or reversed with tocotrienol supplementation. (Tomeo et al, 1995) In a similar study, 25 patients (some with carotid stenosis >49%) received 650 mg of tocotrienols plus tocopherols. A control group of 25 patients, with comparable closure, received a placebo. Each group was evaluated every 6 months for the first year and every year thereafter with ultrasonography. In the placebo group, 15 patients showed worsening of the stenosis, 8 remained stable, and 2 showed some level of improvement. In the tocotrienol plus tocopherol group, 3 patients showed minor worsening, 12 remained stable, but ten patients showed regression of stenosis. Participants observed a simultaneous drop in triglycerides and LDL cholesterol.

The late Karl Folkers, a pioneer in CoQ10 research, observed that drugs affecting HMG-CoA reductase activity caused a simultaneous decrease in CoQ10 levels. The reason for this is that the HMG-CoA enzyme, also, plays a role in CoQ10 synthesis. Individuals using either statin drugs or tocotrienols may wish to increase their intake of CoQ10; a decrease in CoQ10 could negate any benefit garnered from a hypocholesterolemic.

According to Andreas M Papas, Ph.D., appropriate tocotrienol dosages are as follows: 100 IU mixed tocopherols and 100 IU tocotrienols if young and healthy and without a family history of heart disease; 200 IU of mixed tocopherols and 200 IU of tocotrienols for young adults with some cardiac risk factors or healthy people without risk factors up to 50 years of age; 400 IU of mixed tocopherols and 400 IU of tocotrienols for people who have a personal or family history of chronic disease. This dosage includes those who are elderly and stressed, or eat a poor diet.

VITAMIN A AND BETA CAROTENE
Lowers fibrinogen levels and heart disease risks, increases insulin sensitivity

Dr. Dexter Morris et al., at the University of North Carolina, followed the heart health of 1899 men who had elevated cholesterol. During the course of the 13-year study, the blood levels of beta-carotene were monitored. Patients with the highest beta-carotene levels had almost one third fewer heart problems than those with the lowest beta-carotene levels, even though cholesterol levels remained, virtually, unchanged.

Dr. J.E. Manson of the Women's Hospital in Boston reported that those taking 25,000 IU of beta-carotene daily had 22% fewer heart problems and strokes than those taking less than 10,000 I.U. daily. Dr. Monika Eichholzer, scientist at the University of Bern, Switzerland, reported similar findings after following 2974 people for 12 years. Those with the lowest intake of beta-carotene increased their risk of heart problems 150% compared to those with the highest intake.

High vitamin A and beta-carotene serum levels have been reported to reduce fibrinogen levels in humans and animals. Animals fed a vitamin A deficient diet have an impaired ability to break down fibrinogen, but when injected with vitamin A, they produce tissue plasminogen activators that break down fibrinogen, reducing the risk of clot formation.

Vitamin A is beneficial to individuals with Syndrome X, diabetes, and suppressed HDL levels. A study involving 52 patients indicated that vitamin A increased insulin sensitivity, while increasing HDL cholesterol. (Since beta-carotene must be converted in the body to vitamin A, an adaptation some individuals lack, diabetics appear to do better using vitamin A rather than beta-carotene.)

The protection of beta-carotene is not absolute. In fact, if the individual is consuming greater amounts of alcohol, beta-carotene may, actually, increase the risk of intracerebral hemorrhage, according to data released in Arch Neurol. (Leppala et al, 2000)

A blend of phytoextracts, i.e., alpha-carotene, beta-carotene, lutein, and lycopene appear to offer more broad-spectrum protection than using beta-carotene alone. Individuals participating in the Toulouse Study who had higher blood levels of lutein, also, had a lower incidence of coronary artery disease. (Howard et al., 1996) In 1985, the Life Extension Foundation advised members that lutein offered additional protection by entering LDL particles and retarding its oxidation.

Some individuals are susceptible to vitamin A toxicity, even when the dosage is low. This occurs because of a challenged liver and less detoxification mechanisms. Beta-carotene, on the other hand, is regarded as non-toxic. To read more about vitamin A toxicity, consult Appendix A. Appropriate dosage for most individuals: 25,000 IU of beta-carotene or 10,000 to 20,000 IU of vitamin A daily.

READERS GUIDE TO SOURCES OF VITAMIN A, ENHANCERS, AND ANTAGONISTS: The richest source of preformed vitamin A is foods of animal origin, i.e., liver, fish liver oil, milk and milk products, butter, and eggs. Plants contain no preformed vitamin A, but many vegetables and some fruits contain provitamin A carotenoids (the red and yellow pigment of plants). Green foods (asparagus, broccoli, collards, dandelion greens, kale, mustard greens, spinach, Swiss chard, turnip greens), and yellow foods (apricots, cantaloupe, carrots, papayas, peaches, pumpkin, sweet potatoes, and yellow squash) will help meet vitamin A requirements.

Enhancers to vitamin A absorption are vitamin C, zinc, calcium, magnesium, vitamin E, B complex vitamins, choline, and essential fatty acids. Vitamin A antagonists are antibiotics, laxatives, and some cholesterol-lowering drugs (as Questran). Coffee, alcohol, excess iron supplementation, sugar, tobacco, and mineral oil can also, interfere with vitamin A absorption.

VITAMIN C
Lessens risk of stroke and heart attack, strengthens blood vessels, reduces blood pressure, fibrinogen levels, Lp(a), inflammation, and C-reactive protein, promotes gingival healing, is a reliable antioxidant and diuretic, highly beneficial to smokers and those exposed to secondhand smoke

Linus Pauling, a Nobel Prize winner, showed that the body, often, forms atherosclerotic plaque to repair a wound inflicted upon an artery. When adequate amounts of vitamin C are available, an injured artery is repaired without involving atheromatous materials. In the absence of adequate levels of vitamin C, Lp(a), acting as a surrogate for vitamin C, must participate in the repair. Lp(a) does what it must, but the health of the artery is compromised, as plaque is added to the vessel. If ascorbate levels had been adequate, Lp(a) would not have been necessary; without adequate vitamin C, the need for Lp(a) is enormous.

VITAMIN C LOWERS Lp(a)
Kathie M. Dalessandri, M.S., M.D., inspired by a report appearing in the Archives of Internal Medicine relating to the ability of vitamin C to lower Lp(a), wrote the journal about her own experience. Dr. Dalessandri, a general surgeon in Point Reyes Station, California, was displeased with her own Lp(a) levels. She was well aware of the dangers associated with Lp(a), particularly when linked with other risk factors as, a family history of heart disease. Dr. Dalessandri (53 years old at the time) was taking hormone replacement therapy and niacin, but the niacin became problematic and had to be discontinued. After reviewing the literature, she decided upon 3 g/d of both ascorbic acid and L-lysine monohydrochloride, as a natural regime against the elevated Lp(a). Dr. Dalessandri reports that her Lp(a) dropped 14 mg/dl, a reduction of 48% after 6-months. She was, also, pleased that she was able to take vitamin C and lysine without side effects.

Matthias Rath, M.D., in his book, Eradicating Heart Disease, says that animals don't have heart attacks and strokes because their bodies manufacture vitamin C, a genetic adaptation human's lack. Most mammals produce impressive amounts of vitamin C, the human equivalency of 2,000 to 13,000 mg daily. Under periods of stress the same animal's needs for vitamin C may skyrocket, but the body complies by producing prodigious amounts. Man cannot adapt to stress with the same efficiency as lower animals because of a lack of L-gulonolactone oxidase, an enzyme needed to produce vitamin C from glucose. Dr. Rath states that because of this genetic flaw and inadequate dietary vitamin C, cardiovascular disease can emerge as a form of early scurvy.

Jack Challem, co author of Syndrome X, believes that hypoascorbemia (low levels of vitamin C) helped lay the genetic foundation for various risks contributing to cardiovascular disease. For example, too much glucose, which might otherwise be converted to vitamin C, has no other choice but to assume the role of insulin promulgator, advancing the host nearer diabetes.

An ascorbic acid deficit may contribute to the development of vascular lesions (wounds or injuries), by altering collagen metabolism. Vitamin C produces many collagen molecules, supporting a strong and elastic blood vessel wall. Over time, arterial collagen must be replenished. If vitamin C is not present in large enough quantities, collagen is not produced and blood vessels become thin and weak.

Canadian physicians report that arterial tissue levels of vitamin C are much lower in heart patients compared with controls. A five-year study, reported in the British Medical Journal, substantiated the Canadian study. (Nyyssonen et al., 1997) One thousand six hundred and five randomly selected Finnish men, aged 42 to 60 years, entered the study evidencing no signs of preexisting heart disease. After adjusting for other confounding factors, men who were deficient in vitamin C had 3.5 times more heart attacks than men who were not vitamin C deficient.

The risk of stroke increases significantly in vitamin C deficient individuals, according to a report appearing in the journal Stroke. (Tetsuji et al., 2000) The journal Epidemiology reported similar findings, i.e., 42% less cardiovascular mortality in individuals with high vitamin C intake. (Enstrom et al., 1992)

Vitamin C has been found to correlate negatively with hypertension. In a study of 170 healthy men and women (aged 19-70) plasma levels of vitamin C decreased as both systolic and diastolic blood pressure increased. A study carried out at Alcorn State University as a joint effort with the Beltsville Human Nutrition Research Center, showed a significant reduction in systolic blood pressure among 20 participants, using 1000 mg of ascorbic acid daily. At this dose, diastolic blood pressure was not affected. The value of vitamin C as a hypotensive nutrient may come by way of its antioxidant activity, possibly by protecting the body's supply of nitric oxide. (Free radicals appear to lower nitric oxide levels.) Depriving test animals of antioxidants, as glutathione, vitamin E, and vitamin C, resulted in oxidative stress and higher blood pressure.

The heart is one of the most vulnerable of all organs to free-radical oxidative stress. Vitamin C can respond to this risk by exerting its antioxidant properties, acting independently or by prompting the production of other antioxidants. As little as 500 mg/day of vitamin C increased red cell glutathione by 50%.

Vitamin C is beneficial in reducing fibrinogen levels. In a report published in the journal Atherosclerosis, heart-disease patients were given either 1000 mg or 2000 mg a day of vitamin C to assess its effect on the breakdown of fibrinogen. At 1000 mg a day, there was no detectable change in fibrinolytic activity or cholesterol. At 2000 mg of vitamin C a day, there was a 27% decrease in the platelet-aggregation index, a 12% reduction in total cholesterol, and a 45% increase in fibrinolytic activity. (Brodia, 1980)

Inflammation, a newer of the risk factors for heart disease, is reduced by vitamin C. Each winter (in most countries) there is a 15% to 30% increase in deaths from cardiovascular and respiratory disease. Researchers in the UK followed 96 men and women for one year to access the impact of winter stress upon the heart and circulatory system. It appears some of the increase in winter cardiovascular mortality may be related, not only to a rise in fibrinogen, but also to an increase in other inflammatory markers, as CRP. This cycle may be spurred as winter infections increase and vitamin C intake (because of less availability of fruits and vegetables) decreases. The conclusion of the study was that vitamin C might be able to influence cardiovascular risk and the resulting thrombotic tendency, by modulating the inflammatory response to infection. (Khaw et al., 1997)

Vitamin C appears to lessen the negative effects of many other risk factors, including stress, diseased gums, unhealthy diet, and smoking. Smoking, severely, depletes the body of vitamin C; vitamin C, on the other hand, destroys free radicals produced in smoke and protects against endothelial dysfunction. Even secondhand smoke breaks down blood antioxidant defenses and accelerates lipid peroxidation, which leads to an accumulation of LDL cholesterol. Vitamin C, also, protects non-smokers against the harmful effects of free radicals during exposure to passive smoke.

Dosage suggestions: 6 gram daily, in divided dosages. (A loose stool may result from higher doses of vitamin C. Should this occur simply reduce the dose to a level that is not problematic to the bowel.) Under periods of stress, a great deal more vitamin C can be taken without bowel derangement.

READERS GUIDE TO VITAMIN C FOOD SOURCES, ENHANCERS, AND ANTAGONISTS: Berries, citrus fruits, mangos, papaya, pineapple, avocados, and vegetables (asparagus, beet greens, broccoli, Brussels sprouts, collards, cauliflower, cabbage, dandelion greens, mustard greens, sweet pepper, spinach, Swiss chard, tomatoes, turnip greens, potatoes, and watercress are vitamin C rich sources. (Raw foods represent excellent choices, having escaped the rigors of processing and preparation.)

All vitamins and minerals work synergistically to enhance vitamin C absorption, particularly the bioflavonoids. Alcohol, coffee, sulfa drugs, antibiotics, analgesics, antidepressants, anticoagulants, oral contraceptives, and steroids can drain vitamin C from the body. Smoking seriously depletes vitamin C levels.

VITAMIN E
Prevents plaque formation, protects LDL from oxidation, strengths blood vessels, prevents blood viscosity, helpful in atrial and ventricular fibrillation, is an antioxidant and anti-diabetic nutrient, improves insulin sensitivity, protective to smokers, reduces CRP, has diuretic activity, beneficial to those with hemochromatosis

Dr. Richard Passwater commented, in June of 2001, that good research is timeless. The following is an example of an excellent study that should not be lost in the archives.

In 1974, Dr. Passwater enrolled 17,894 persons (ages 50 to 98) in a study to determine the effects of long-term vitamin E supplementation. He found the length of time the individual used vitamin E was more important than the amount of the nutrient used. The trend was especially apparent beyond nine years of usage. Taking 400 IU of vitamin E daily for 10 years or more, dramatically, reduced the occurrence of heart disease prior to 80 years of age. Among the persons taking vitamin E over 10 years, only 4 had heart disease out of a total of 2,508. Ordinarily, in a sample of that size, approximately 836 persons would be expected to suffer from heart disease.

An ongoing study involving a group of nurses, 87,245 women ages 34 to 59, (study begun in 1980) and 39,910 male health professionals ages 40 to 75 (study begun in 1986) showed a significant relationship between the use of vitamin E supplements and a reduced risk of heart disease. (Stamfer et al., 1998) (Rimm et al., 1993) Trial participants taking at least 100 IU daily of vitamin E (an extremely low dose) decreased their risk of heart disease by 40%. Impressive as these results are, a study appearing in the Lancet may have eclipsed all others when they reported that 2000 individuals with established heart disease (supplemented with 400-800 IU of vitamin E daily) reduced the incidence of non-fatal heart attacks by 77%, compared to a similar group not receiving vitamin E.

These dramatic results occur, in part, because vitamin E prevents white blood cells from adhering to arterial walls. Researchers from the University of Texas Southwestern Medical Center confirmed that when monocytes are suppressed from bonding to the artery, a primary step in arterial closure has been avoided. Also, vitamin E renders the blood less "sticky" and platelets less prone to clump, according to John F. Keaney, M.D., Boston University School of Medicine.

Individuals with poor lipid profiles, and suffering from edema, profit from vitamin E supplementation. Typically, vitamin E reduces total cholesterol by 15%, LDL by 8%, and thromboxanes by 25%. When children with dropsy were supplemented with 300 IU of vitamin E, their edematous tissues returned to normal.

Free radicals activate a gene that encourages overgrowth of smooth muscles in the blood-vessel walls, a process that contributes to closure. Vitamin E, a reliable antioxidant, has the opposite effect, i.e., it turns off the gene responsible for smooth muscle proliferation. Vitamin E's antioxidant powers extend to protect the cells and organs (particularly the lungs) from damage caused by smoking.

Animals, coronary artery occluded for experimentation, experienced a significant decrease in the ventricular fibrillation threshold; those supplemented with vitamin E observed no decrease in the threshold. French scientists confirmed the results of the animal studies, reporting that vitamin E is effective against both atrial and ventricular fibrillation. Ventricular fibrillation is a cardiac arrhythmia marked by rapid, disorganized depolarizations of the ventricular myocardium. The blood pressure falls to zero, resulting in unconsciousness; without defibrillation and resuscitation, death can promptly ensue.

A newer finding, relating to the functions of vitamin E is that high dose vitamin E lowers C-reactive protein (CRP). Administering 1200 IU of alpha-tocopherol (daily for three months) lowered CRP levels by 30%. CRP levels remained reduced 2 months post supplementation.

Vitamin E, usually, reduces blood glucose levels in diabetics by 12%, often lessening insulin requirements. Because of this, diabetic individuals wishing to use vitamin E should begin with 100 IU daily and gradually increase the dosage, allowing for the appropriate insulin adjustment.

According to Dr. Ishwarlal Jialal and Dr. Sridevi Deveraj (University of Texas Southwestern Medical Center at Dallas), diabetics have increased inflammation and are more prone to cardiovascular disease. Vitamin E lowered levels of interleukin-6, an inflammation-producing cytokine, by 50%. Vitamin E, by decreasing inflammation, may contribute to a reduction in cardiovascular disease in both diabetic and non-diabetic subjects. (For an in-depth review of CRP, consult C-reactive protein under Newer Risk Factors and Link Between Infections and Inflammation In Heart Disease in this protocol.)

Vitamin E appears to be decreased in patients with hereditary hemochromatosis or iron overload. Iron loading, in experimental studies, significantly decreases hepatic and plasma vitamin E, a shortage amenable with supplementation. Free radical index markers increase three- to fivefold in iron-loaded livers, but supplementation with vitamin E has been shown to reduce these levels by about 50%.

The type and blend of vitamin E used affects the end results. Studies have shown that alpha-tocopherol may not protect as aggressively against coronary heart disease unless it is combined with the gamma-tocopherol form. Both alpha-tocopherol and gamma-tocopherol can decrease platelet aggregation, inhibit blood clot formation, protect LDL cholesterol against oxidation, and increase endogenous SOD production (an enzyme with antioxidant activity); gamma-tocopherol, however, shows greater activity on each function.

Gamma-tocopherol, though the most abundant form of vitamin E, has a couple of factors working against its utilization. For example, gamma-tocopherol can be obtained from foodstuffs, but it is poorly retained, and much of it is excreted in urine after being metabolized by the liver. And a protein, referred to as alpha-tocopherol transfer protein, identifies and selectively chooses alpha-tocopherol over other forms of vitamin E. As a result, alpha-tocopherol is found more abundantly in lipids, blood, and body tissues. Unfortunately, this scenario does not allow for maximum protection against free radical attack.

Individuals relying upon the cardio-protective effects of vitamin E should make sure that part of their intake includes the gamma-tocopherol form, but the complexing process determines benefit. A union of alpha-tocopherol (80%) with gamma-tocopherol (20%) appears ideal; too much alpha-tocopherol may oppose the antioxidant qualities of gamma tocopherol. Suggested dosage: 400-1200 IU/day. Initially, blood pressure rose in approximately one-third of hypertensive individuals treated with vitamin E. Therefore if hypertensive, begin with 100 IU/day for one month and add 100 IU each month until 400 IU/day is reached. Comment: Pracon Inc., a hospital-outcomes analysis firm in Reston, Virginia estimated that health-care expenses could be reduced by $7.7 billion annually if consumers took vitamin E supplements.

READERS GUIDE TO VITAMIN E FOOD SOURCES, ENHANCERS, AND ANTAGONISTS: Vitamin E, the most widely available nutrient in foodstuffs, is found in wheat germ, whole grains (brown rice, cornmeal, oatmeal, and wheat), vegetable oils (soybean, corn, and cottonseed), egg yolk, butter, milk fat, meat (especially liver), dark green leafy vegetables, legumes, nuts, and seeds.

Vitamin E enhancers are vitamin A, the B-complex, vitamin C, magnesium, manganese, selenium, inositol, and essential fatty acids. Excessive fat intake should be avoided as well as birth control pills and mineral oil for optimal vitamin E absorption.

VITAMIN K
Reduces calcium overload, inflammation, CRP, risk of thrombosis, and progression to valvular stenosis, has a role in glucose management

Important as calcium is as a hypotensive and antiarrhythmic mineral, it has a detrimental side if it seeps into the arteries. Arterial calcification, common to the aging process, is a risk factor leading to the development of heart disease, atherosclerosis, and mitral and aortic valve stenosis. Harvard Medical School announced that about 25% of adults over 65 years of age have arterial calcification, increasing their risk of severe heart disease by 50%. (Harvard Heart Letter, 1999) The Framingham Heart Study determined, however, that the risks imposed by aortic calcification are not restricted to the senior population; 35-year-old men with aortic calcification had a 7 times increased risk of dying of a sudden heart attack.

Vitamin K appears to keep calcium in bones and out of arteries and valves. This is vitally important, for so interrelated is bone loss to cardiovascular disease, measuring bone density has become a predictive factor. A one standard deviation from the norm of bone density equals a three times increased risk of stroke. In 1999, the cumulative results of 8 years of research determined that severe kyphosis (humpback) increased the risk of dying from a lung-related disorder, as a blood clot, 2.6 times.

Rats given the anticoagulant drug warfarin (Coumadin), which depletes the body of vitamin K, developed extensive arterial calcification. Conversely, supplying adequate amounts of vitamin K (as much as10 mg daily) reduced calcium-induced atherosclerosis. (Vitamin K is not stored in the body, and is therefore nontoxic at higher doses.)

A group of animals, with induced atherosclerosis (diet based on vitamin D and cholesterol) were given either vitamin K (100 mg/kg of body weight) or vitamin E (57 IU/kg) to assess reversal of atherosclerotic persona. At the conclusion of the study, the control group, i.e., those not treated, showed aortic calcium of 17.5 u/mg; those receiving the vitamin K had approximately 1 u/mg of calcium and vitamin E reduced it even further. (For more information relating to the calcification process, consult the section devoted to valvular disease in this protocol.)

With age, levels of interleukin 6 (IL-6), a cytokine, increase. An imbalance results as IL-6 crowds out other cytokines, a process creating inflammation. Vitamin K reduces levels of IL-6, and as inflammation is reduced the risk of developing a blood clot decreases. Since C-reactive protein is synthesized in response to IL-6, it appears vitamin K may be valuable in reducing elevations in C-reactive protein.

Japanese researchers, also, found that a vitamin K deficiency can mimic the symptoms of diabetes; the pancreas, which produces insulin, has the second highest levels of vitamin K in the body.

High doses of vitamin K are contraindicated if using blood thinners. For more information regarding low-dose vitamin K supplementation among asymptomatic patients taking warfarin, please consult the section entitled Fibrinolytic Activity.

THE CALCIUM PARADOX
It is important to look at the ways calcium can become an atheromatous material. Most body stores of calcium are found in the bones and teeth and 1% in the bloodstream. This 1% performs so many vital functions, including cardiac health, that the body vigorously defends this minute percentage. If inadequate calcium is available, vitamin D is mobilized in the kidney and rushes to the intestinal wall to pull more calcium into the bloodstream. If inadequate amounts of vitamin D are available, the parathyroid gland delivers a message to bones to release calcium. Because the calcium mass in the bone is so great, it is easy for too much of the mineral to be extracted, overwhelming the amount needed in the blood. With no place to go, the excess calcium ties up in soft tissues, i.e., the lining of arteries and brain tissue.

Ineffective calcium regulation (leading to calcium excess) also affects arterial plaque, causing it to become harder but more brittle. (Harvard Heart Letter, 1999) This occurs as calcium deposits in the blood attach to cholesterol deposits on the walls of arteries, making an almost impenetrable union. (Shappell, 2000) This process further narrows the artery, causing symptoms ranging from fainting spells to sudden death due to abrupt changes in blood pressure. (Doss, 2001)

It is important to grasp that excesses of calcium (potentiating arterial disease) come, essentially, from the bone. Furthermore, the results of a test indicating adequate blood calcium levels, can be totally misleading for the supply may have been extracted from the skeletal system. Because secondary pathways, important in maintaining homeostasis, are not well regulated, it is imperative to maintain adequate calcium levels without summoning the parathyroid gland into service.

READERS GUIDE TO VITAMIN K FOOD SOURCES AND ANTAGONISTS: Though friendly bacteria in the intestines synthesize the majority of vitamin K, the total requirement cannot be met by bacterial synthesis alone. Vitamin K rich foodstuffs are liver, green leafy vegetables (especially broccoli, turnip greens, lettuce) and cabbage. Other sources are alfalfa, meats, egg yolks, blackstrap molasses, asparagus, Brussels sprouts, cauliflower, oatmeal, rye, safflower oil, soybeans, and wheat. Antibiotics increase the need for vitamin K and vitamin E (doses >600 IU) antagonize vitamin K activity.

ZINC
Important in weight and blood pressure management, regulates glucose/insulin levels, increases testosterone levels

Zinc, the second most abundant trace mineral in the body, is important in glucose and insulin management, as well as weight control. Individuals with the lowest dietary intake of zinc showed the greatest prevalence of coronary artery disease, diabetes, and obesity; conversely, as patients made dietary corrections to include more zinc in their diet, blood pressure, blood glucose, triglycerides, and central abdominal obesity decreased.

Zinc is a vital component of insulin, but its worth extends to the cellular receptors, where zinc increases insulin sensitivity. When zinc levels are too low, the pancreas cannot supply enough insulin to control blood glucose levels and the amount that is produced is less functional.

The emphasis is upon correcting a zinc deficiency (that may be contributing to diabetes) not dosing at will. The journal Diabetes reported that administering large doses of zinc sulfate (220 mg/90 mg actual zinc/three times a day) increased fasting blood glucose levels from an average of 177 mg/dL to 207 mg/dL. (Raz et al., 1989) Glycosylated hemoglobin levels, also, increased among a group of type I diabetics receiving 50 mg of zinc per day. (Cunningham et al., 1994) Considering these poor statistics, if a prediabetic or diabetic is using zinc, no more than 15 mg (the RDA) should be used per day without close blood glucose monitoring.

Zinc assists in controlling weight through various mechanisms. For example, if over-supplied, copper can increase fat stores and triglyceride synthesis. Zinc is a known antagonist to copper, meaning zinc can interfere with copper absorption. This is good news for the dieter, for as zinc crowds out copper fewer triglycerides appear in the bloodstream and less fat throughout the body. Zinc, also, benefits the dieter by influencing blood levels of leptin, a hormone secreted by fat cells that modulates metabolic rate and appetite. Zinc (30-60 mg daily) increases blood leptin levels, and, as a result, the feeling of satiety. With the help of leptin, the brain receives the signal that enough food has been consumed, and the dieter has the willpower to eat less.

Low levels of testosterone appear to advance the atherosclerotic process by increasing fibrinogen and cholesterol levels, as well as increasing blood pressure. For the cardiovascular patient with low testosterone levels, a healthier heart profile may emerge with zinc supplementation. The following study illustrates zinc's ability to increase testosterone levels. Twenty-two men with chronically low testosterone levels, were given 50 mg of zinc sulfate daily for 45 to 50 days to promote fertility. (All of the 22 had experienced infertility longer than 5 years.) The 22, initially low in testosterone, had a significant increase in testosterone during the zinc therapy. In fact, 9 out of the 22 wives became pregnant during the study. (Netter et al., 1981)

It appears that zinc therapy, though beneficial to most, is not risk free. Occasionally, emphasizing zinc without copper can lead to copper-deficiency anemia, lower levels of HDL, and higher levels of LDL cholesterol; for some, the lack of balance between the two trace minerals can result in an irregular heartbeat. (Klavay, 1975) Copper is not risk free either, for it can potentiate free radical activity.

Epidemiologic and metabolic data are convincing concerning the theory that an imbalance (in regard to zinc and copper) is a major factor in the etiology of coronary heart disease. For this reason, if consuming over 50 mg of zinc daily, 2 mg of copper is recommended several times a week. Since copper is widely distributed in select foods, as poultry, organ meats, shellfish, oysters, chocolate, nuts, dried legumes, and cereals, 2 mg a day can, usually, be obtained by favoring dietary selections from this list.

READERS GUIDE TO ZINC FOOD SOURCES, ENHANCERS, AND ANTAGONISTS: Zinc content is highest in flesh foods, as meats, poultry, liver, and oysters. Foods such as legumes and whole grain products are, also, sources of zinc, but larger amounts must be consumed to deliver significant amounts. Other good sources of zinc per kcal (according to Whitney, et al., 1998) are spinach, broccoli green peas, green beans, tomato juice, plain yogurt, Swiss cheese, tofu, shrimp, lean ground beef, lean ham, lean sirloin steak, crab, and turkey (dark meat).

Vitamin A, B3, B6, vitamin C, calcium, copper, magnesium, essential fatty acids, and amino acids enhance zinc absorption. Alcohol, oral contraceptives, excesses of copper and calcium, saturated and trans fats, steroids, obesity, and smoking interfere with zinc utilization. Diarrhea, kidney disease, cirrhosis of the liver, and diabetes can, also, contribute to zinc deficiency. Perspiration lowers the status of many minerals, including zinc. Zinc and iron oppose each other and should not be taken at the same time.

DOES SODIUM RESTRICTION LOWER BLOOD PRESSURE?

An evaluation of a hypertensive patient should include measuring plasma renin activity (PRA) to determine if renin is a factor in the pathogenesis of elevated blood pressure. Renin is an enzyme secreted by the juxtaglomerular apparatus of the kidney in response to many cardiovascular factors, such as a fall in blood pressure or plasma volume and/or sodium depletion. In an attempt to maintain homeostasis, renin is released to increase blood pressure. Renin increases blood concentrations of angiotensin I, which is converted to angiotensin II. Angiotensin II causes an increase in aldosterone secretion, a sequence that increases peripheral vascular resistance and blood pressure.

In order to stimulate renin release and prepare the patient for the PRA test, the individual is told to follow a diet very low in sodium for 3 days prior to the test. Patients with low renin levels respond best to salt depletion through sodium restriction and diuretic therapy. Those with high baseline renin levels will not respond to sodium restriction. Note: According to Jeff Bland, Ph.D., most individuals who suffer from essential hypertension are not salt sensitive. Putting those individuals on a rigorous salt restricted diet has little impact upon their hypertension. Conversely, if an individual is salt sensitive, sodium restriction will have a profound effect upon modulating blood pressure. This is an example of utilizing the correct dietary program for the right genotype.

Another rationale to support sodium as an attendant to essential hypertension involves hyperinsulinemia. Excesses of insulin enhance renal sodium retention and increase blood pressure. (Zavaroni et al., 1992) The finding that blood pressure increases or decreases when lesser or greater amounts of insulin are administered to obese, hypertensive patients supports Zavaroni's work. (Tedde et al., 1989) (Randeree et al., 1992) Tissue resistance also appears to play a role in hypertension by altering internal sodium and potassium levels. Disturbance in mineral distribution increases peripheral vascular resistance and subsequently blood pressure. (Zavaroni et al., 1992)

The most effective dietary treatment for hypertension appears to be weight loss and a dietary intervention to increase calcium, magnesium, and potassium intake. Results of the Dietary Approaches to Stop Hypertension Study (DASH), published in 1997, were that a diet rich in fruits, vegetables and low-fat dairy products, significantly, lowered blood pressure. These foods are excellent sources of potassium, magnesium, and calcium, accounting for the success of the diet. In the study, blood pressure reduced by 5.6 and 2.8 mmHg (systolic and diastolic pressures) making dietary intervention comparable to first generation anti-hypertensives. Weight loss and dietary manipulation appears to control hypertension in nearly one-half of individuals with high blood pressure.

CAN WHAT YOU DRINK MAKE A DIFFERENCE?

Alcohol
Endorsing alcohol consumption is difficult considering the number of health risks imposed by drinking. But, when considering the health of the heart and vascular system, statistics appear to flip in favor of moderate alcohol consumption. Studies involving atherosclerosis (disease authenticated by cardiac catheterization or autopsy) show less arterial closure among persons who consume moderate amounts of alcohol. A moderate drinker, in fact, decreases the possibility of heart disease by 30% to 50%. This is true for both men and women, particularly imbibers middle-aged or older.

Encouraging as this information is, the line is extremely narrow in regard to the amount of alcohol one can consume and still reap benefits. For example, teetotalers or occasional drinkers lose the alcohol advantage because of inconsistent consumption. Conversely, persons consuming three or more drinks per day experience a rapid rise in total morbidity, i.e., cardiomyopathy, hypertension, and hyperhomocysteinemia, as well as mortality. The bottom line indicates that non-drinkers, as well as individuals who aggressively imbibe, have a higher risk of succumbing from heart disease than an individual consuming one to two drinks per day. Unfortunately, current studies reflect too many inconsistencies to recommend the preferred type of alcohol yielding maximum cardiac protection. (Rimm et al., 1996) At this time, all drinks appear equally beneficial to the heart, if the intake is moderate.

It is speculated that about 50% of the protective nature of alcohol is due to alcohol's ability to increase HDL cholesterol. Another edge comes by reducing blood glucose and insulin levels, according to Diabetes Care. (Facchini et al., 1994) It appears no advantage is siphoned from alcohol in regard to lowering either blood pressure or LDL cholesterol levels, but the blood clotting mechanism is altered by alcohol consumption. It is debatable how alcohol accomplishes this. Perhaps, it is by influencing coagulation factors, as PAI-1, t-PA, and the activity of platelets.

Reports appearing in the Lancet added to the benefits obtained from alcohol, citing the antioxidants found in red wine and dark beer. (Maxwell et al., 1994) Antioxidants, regardless as to their source, always play heroic roles in heart health. Interestingly, alcohol is still able to convey a cardiovascular advantage, even in light of a poor diet or cigarette smoking.

Is alcohol the utopia we are all searching for? Probably not, considering the dangers imposed by excessive consumption. Persons with a personal or family history of alcoholism, those with hypertriglyceridemia, pancreatitis, liver disease, certain blood disorders, hypertension, as well as pregnant women are not candidates for either beginning or continuing to drink alcohol. Dieters should not forget that alcohol is a significant source of calories as well as carbohydrates. It is, also, important to recall that drug/alcohol interactions can be fatal. Yet, after acknowledging the negatives, if current consumers of alcohol all abstained from drinking, about 80,000 excess heart deaths would occur annually. Though the research is compelling, alcohol should never be considered a treatment for either Syndrome X or heart disease.

GREEN TEA
The pleasure of a cup of green tea is well confirmed, but it appears to accomplish far more than satisfy the palate. Published literature confirms the hypolipidemic nature of green tea, reporting decreases in triglycerides and LDL cholesterol, while increasing the beneficial HDL cholesterol. J Nutr Biochem, also, acknowledged that green tea suppressed the oxidation of LDL cholesterol, further deterring the atherosclerotic process. (Zang et al, 1997)

Some researchers liken green tea to aspirin because of similar therapeutic qualities. For example, green tea, like aspirin, inhibits thromboxane A2; inhibition of thromboxane A2 lessens the risks of blood clot formation and the dangers imposed by arterial constriction. Also, information published in Beyond Aspirin (Newmark et al., 2000), states that green tea contains salicylic acid, a natural-occurring Cox-2 inhibiting compound. At one time, the ability to inhibit cyclooxygenase and inflammation was considered a function common to aspirin, not green tea.

Heart attacks and strokes are less likely to occur if neither fibrinogen levels nor the activity of the platelet-activating factor (PAF) become excessive. Green tea lowers fibrinogen and is a PAF inhibitor. A 4-year study involving 5910 Japanese women (more than 40 years of age) showed twice as many strokes among trial participants who were not green tea drinkers compared to those who did drink green tea.

A cup of green tea appears beneficial to hypertensives through various mechanisms. The loss of arterial elasticity (arteriosclerosis) is one cause of high blood pressure. Youthful arteries expand and contract in compliance with the heartbeat to move the blood to peripheral sites. Damaged vessels are unable to participate in this ritual. Green tea (by inhibiting thromboxane) reduces arterial constriction, and consequently, blood pressure is reduced. Also many anti-hypertensive drugs act as an ACE (angiotesin-converting enzyme) inhibitor, meaning angiotensin pathways are disrupted. Without interruption of this feed back loop, blood vessels vasoconstrict, water is retained, and blood pressure increases. Green tea breaks this sequence, acting as a natural (though mild) ACE inhibitor.

Green tea reduces the expected glucose and insulin rise after a carbohydrate load (50 gram). High blood glucose and insulin levels predispose diabetes and cardiovascular disease. Also, catechin, the most prevalent polyphenol in green tea, appears to act as a natural calcium channel blocker (beneficial in arrhythmias and hypertension).

Green tea, an antioxidant, helps remove excess iron from the liver.
Individuals with hemochromatosis should drink the tea or use 4 to10 green tea extract capsules containing at least 250 mg of active polyphenols per capsule. Research suggests that decaffeinated green tea has a different therapeutic disposition than that containing caffeine and is more effective in reducing iron overload. Note: Caffeine drinks are not appropriate for sympathetic dominant individuals and those taking beta-adrenergic drugs.

Similar as green tea and aspirin are in their defensive mechanisms, it would not be wise for an individual, relying upon aspirin as a cardio-protective, to depend only upon green tea to the exclusion of aspirin.

Nuts….a heart food
According to a report published in the Am J Clin Nutr, one of the most unexpected and novel findings in nutritional epidemiology in the past 5 years has been that nut consumption protects against ischemic heart disease (IHD). (Sabate, 1999) Phytonutrients in nuts, as luteolin (a flavonoid), tocotrienols, fiber, fatty acids, amino acids, and vitamins/minerals appear to work synergistically to provide heart protection, lower blood pressure, reduce the risk of stroke, and increase longevity. The protective affect of nuts applies to men and women (both black and white), all ages, smokers, and sedentary individuals.

Of the tree nuts, walnuts are unique because they are a rich source of linolenic acid. Almonds are a good source of vitamin E and calcium; peanuts provide folate (important in controlling homocysteine) and resveratrol (inhibits blood clots and the inflammatory process). Most nuts are good sources of arginine and fiber.

The Adventist's Health Study reported that individuals who ate nuts 1-4 times per week had a 22% reduced risk of acute myocardial infarction. (Fraser et al., 1992) Eating nuts more than 5 times per week resulted in a 51% reduced risk compared to individuals who consumed nuts less than 1 time a week. Persons consuming nuts more than 5 times per week lowered their lifetime risk of IHD by 12% and men who developed the disease did so 5.6 years later than did men who consumed nuts infrequently.

Loma Linda University showed that eating a diet in which 20% of the calories came from walnuts improved lipid parameters more than the low-fat diet recommended by the American Heart Association. A nutritionist at Pennsylvania State University announced that a diet that provided 36% of its calories from fat, mostly from peanuts and peanut butter, lowered LDL cholesterol and triglycerides by more than 10%, whereas a standard low-fat cholesterol-lowering diet raised triglycerides by 15%. In neither the almond nor the peanut study did the participants gain weight.

AUTONOMIC BALANCING…RIGHT MESSAGES…GOOD RESULTS
Much of the data collected from the astute work of Dr. Nicolas Gonzalez, a New York physician dealing chiefly with cancer patients. Dr. Gonzalez uses autonomic balancing as part of a comprehensive nutritional approach to treat cancer. The concept of autonomic balancing extends, however, to include other diseases, including heart disease.

The autonomic nervous system, consisting of the parasympathetic (PNS) and the sympathetic divisions (SNS), play major roles in heart function. For example, when the PNS is active, heartbeat, blood pressure, and respiration rate tend to be decreased, as well as the activity of the adrenal glands. Conversely, when the SNS is dominant, the brain signals the adrenal glands (small organs located on top of the kidneys) to supply adrenaline, the stress hormone. Adrenaline rushes through the bloodstream to all tissues, organs and glands, heightening their responsiveness. Blood pressure, heart rate, blood glucose levels, respiration, and perspiration increases. It is referred to as the "fight or flight" division, for a general state of excitement and preparedness is evidenced.

If the individual is healthy, an adrenaline serge is inconsequential. But, if the heart is diseased or damaged, the sympathetic stimuli can be dangerous, even deadly. A sympathetic dominant/cardiac patient should avoid even short-term stimulation, for the heightened response may be just enough to push the system over the edge. Type A individuals, often, live with chronic stimulation of the SNS, a burdening handicap to long-term survival.

Though each of us is born with a propensity toward a sympathetic, parasympathetic or balanced response from the ANS, Dr. Gonzalez is finding that chemical pollutants and lifestyle abuses can shift balance and disrupt the natural tendency of the individual. If either division becomes abrasively dominant, the risks imposed upon the heart can be meaningful. For example, if the PNS is goaded into increased responsiveness, the risks are as genuine as if the SNS were exalted. A heart, receiving its instructions from the PNS, may become a bit passive and cardiac output lethargic. Unable to cope with a one-sided response from the ANS, the heart can make fatal errors. Drugs, supplements, and lifestyle should, always, complement the lagging system; never should selections prompt greater activity in an already overpowering division. A lack of homeostasis (internal balance) seriously bewilders the action of the heart.

The sympathetic and parasympathetic nervous systems are a two-neuron system, meaning that two sets of nerves interconnect in the ganglion. Minerals play an extremely important role in the message sent to organs and glands from the ANS. For example, Dr. Gonzalez explains that magnesium blocks transmission between the two nerves and the ganglion, and is regarded as the very best "turn-off" for sympathetic arousal. In the other hand, calcium rouses activity in the SNS. Potassium, though not a sympathetic toner, acts directly upon the PNS encouraging increased responsiveness. Exercise quiets the SNS, burning off sympathetic hormones, making stronger parasympathetic expression.

The pH of a parasympathetic dominant tends to be alkaline; the pH of a sympathetic dominant is acid. This principle may best explain the benefit some individuals enjoy when eating a predominantly fruit/vegetable diet, with protein sources limited to smaller amounts of fish and chicken. The alkalinity of a plant-based diet makes the response from the PNS stronger and the activity in the SNS more subdued. Conversely, red meat turns on the SNS and is beneficial to an individual with an overactive parasympathetic system. In fact, Dr. Gonzalez feels a cholesterol level between 210 to 220 mg/dL, is fitting for a parasympathetic, for the cholesterol then assumes the nature of a powerful antioxidant. Comment: It is important not to minimize the deliberation Dr. Gonzalez exercises in selecting an appropriate diet for a patient. Ultimately, there are 10 basic diets with tens of variations, ranging from strict vegetarian to red meat depending upon the degree of autonomic imbalance.

A cardiac patient should seek a physician who can determine metabolic type; assumptions concerning metabolic disposition is not adequate. A physician who can make this determination will, also, make cohesive choices, regarding pharmaceuticals, diet, and exercise, eliminating conflicting messages being delivered to the heart.

BETA-BLOCKERS

Since over expression of the beta-adrenergic system can result in an irregular heartbeat, scientists searched for drugs that could block its activity. Propranolol became the granddaddy of the family of beta-blockers and is one of the most prescribed drugs in America for arrhythmias, hypertension, and angina pectoris.

Beta-blockers bind to specific receptors on nerve endings in an effort to control blood pressure, anxiety, and arrhythmias occurring before or after a heart attack. The binding process blocks the effects of impulses transmitted by the adrenergic postganglionic fibers of the sympathetic nervous system. As beta-blockers compete with epinephrine (also known as adrenaline) for receptor sites, the excitory nature of epinephrine is disrupted. Beta-adrenergic receptors are located mainly in the heart, lungs, kidneys, and blood vessels.

Conventional cardiologists conducting propranolol studies reported satisfaction with beta-blockers, citing fewer second heart attacks among users and a 26% reduction in heart mortality. Many patients were less pleased with beta-blockers, describing clinical depression, erectile dysfunction, and fatigue, as compromising factors. Also, beta-blockers have been associated with an increased risk of developing diabetes, by impairing insulin sensitivity. A better choice for a hypertensive individual with a propensity for diabetes appears to be alpha 1-blockers, which actually improves insulin sensitivity. Newer beta-blocking drugs such as Toprol are now considered superior to propranolol.

CALCIUM CHANNEL BLOCKERS

The heart is controlled by tiny electrical impulses, not unlike a pacemaker, that regulate the heart. Calcium plays a key role in regulating the heart's response to these electrical signals. It flows between the heart cells and surrounding fluid through a sort of "chemical turnstile" or calcium channel. The more calcium that gets through the turnstile before the electrical signal is received, the more strongly the heart contracts, an effort that increases the heart's workload. Calcium channel blockers do not totally block movement through the turnstile, but it, significantly slows it down. For some, this process lessens the labor required of a damaged heart, signaling it to slow down and take it easy. Because calcium channel blockers dilate the arteries and reduce resistance to blood flow, they are, also, widely used to control hypertension.

The FDA first approved calcium channel blockers in 1982 for the purpose of treating arrhythmias. Popular as "blockers" are, the tide has been a bit turbulent for both calcium channel blockers and beta-blockers. It has been determined that Procardia, a calcium channel blocker, can actually potentiate a fatal heart attack. Nearly twice as many users are likely to die within 5 years compared to those treated with other drugs.

A few of the side effects associated with both calcium channel blockers and beta-blockers are congestive heart failure, lightheadedness, fatigue, hypotension (low blood pressure), shortness of breath, and bradycardia (heartbeat less than 60 beats per minute). The Lancet reported that calcium channel blockers, often hailed as an ace in cardiac pharmacology, increase the risk of developing cancer. (Pahor et al., 1996) Among the 5,000 men and women enrolled in a verapamil, diltiazem, and nifedipine study, the risk of cancer increased by 72%. In addition, Professor Bruce Psaty of the University of Washington reported that a study involving 2,600 hypertensive patients showed the risk of a heart attack increased up to 60% while taking calcium channel blockers. (Douglas, 1996)

Dispersed throughout the material are recommendations for natural products that mimic the activity of beta-blockers (L-carnitine, hawthorn, and magnesium) and calcium channel blockers (angelica, green tea, L-carnitine, magnesium, green tea, and proanthocyanidins) but with a wider window of safety, compared to drugs.

INVASIVE vs. NONINVASIVE TESTING AND HEART SURGERY
Facts to consider before a final decision is made

Invasive heart treatment ranks ninth among the top 10 causes of death. Because of the obvious seriousness of any procedure involving the heart, consenting to invasive testing and surgery should be made rationally rather than emotionally. The intent of this protocol is not to steer the patient in regard to cardiac testing and treatment, but rather to enlighten the reader concerning both options and risks. Fortunately, researchers have removed some of the uncertainties from the dilemma.

Detection of a heart problem can be made by several noninvasive tests, i.e., medical history, physical examination, electrocardiogram, stress tests, blood tests, and an echocardiogram. An echocardiogram provides a graphic outline of the movements of the heart structures, showing the valves and the action of blood flowing through them, the ability of the left ventricle to pump blood, the walls of the heart (considering thickness), and an assessment of the membrane around the heart (the pericardium) to look for accumulations of fluid. It does not show the coronary arteries well enough to determine blood circulation directly to the heart; for this evaluation the echocardiogram should be combined with a cardiac stress test. This combination will show the workings of the various parts of the heart during stress compared to rest.

Blood tests are valuable for they confirm or refute uncertainties arising from early stage diagnosis of a heart attack. Creatine kinase (CK), the most commonly used cardiac blood test, troponins, and a small fraction of the CK enzyme (CK-MB) are heart damage markers or cardiac enzymes measurable in the blood. CK-MB shows an increase above normal about six hours after the onset of a heart attack. It reaches its peak level in the blood in about 18 hours and, usually, returns to normal in 24-36 hours. The time frame may vary if the heart attack is classified as "big," with the peak level and the return to normal delayed in this incidence.

Blood tests to measure troponins, specifically T (cTNT) and troponin I (cTNI), cardiac muscle proteins, have been developed. These proteins control the interaction between actin and myosin, muscle proteins that contract or squeeze the heart muscle. Identifying troponins specific to heart muscle allowed the development of blood assays that can detect heart muscle injury with great sensitivity and specificity. The normally low level of cTNT and cTNI increases, substantially, within four to six hours of heart muscle damage. A peak occurs at 10 to 24 hours and can be detected for a week or more thereafter.

It is now considered possible to use troponin testing to identify individuals at either low or high risk for a coronary event. Even modestly elevated troponin levels are associated with larger numbers of tiny coronary artery blood clots, complex arterial lesions, and impaired blood flow through the vasculature. Compared to patients with the lowest levels of troponin T, those with the highest troponin T levels are almost 13 times more likely to die over a 37-month period, according to research appearing in the New England Journal of Medicine. (Lindahl, et al., 2000)

The type of troponin blood test used by most clinical laboratories is troponin I. If levels exceed 0.4 ng/mL, antiplatelet/antithrombotic therapy should be considered. This can be administered though drugs and/or selections made from the Therapeutic Section of this material.

Angiograms
An angiogram, referred to as cardiac catheterization, is a mechanism in which coronary arteries are luminated by injections of dye, a process that aids in diagnosing blocked arteries. A catheter is introduced through an incision into a large vein, usually of an arm or a leg, and threaded through the circulatory system to the heart. As the dye wends its way through the vasculature, blockages are detected by changes in flow rate at points of occlusion. An angiogram is a popular diagnostic tool, but it is not without risks, i.e., local infection, cardiac arrhythmia, and thrombophlebitis.

Data reported in JAMA debate the relevancy of widespread angiogram usage. (Graboys et al., 1987) A study chronicled 168 patients who were advised to have an angiogram to determine the need for either angioplasty or cardiac surgery. Eighty percent or 134 of the 168 patients, who were evaluated noninvasively, were determined not to need catheterization. From the 168 patients, an annual fatal heart attack of 1.1% was observed over a five-year period compared to a 5%-10% mortality rate from coronary bypass surgery and a 1%-2% mortality rate from angioplasty. The conclusion of the published report was that noninvasive testing to access the heart's performance is a better and safer determinant of a suitable therapeutic program than searching for blocked arteries. If the patient fails some of the noninvasive tests, the angiogram is warranted to determine the need for surgery.

MAGNETIC RESONANCE IMAGING (MRI)
Up to 70% of heart attacks occur in blood vessels that appear normal on an angiogram. The journal Circulation reported that plaque without any calcium deposits is not detectable by angiograms or CAT scans, but they are the most common cause of sudden death from a heart attack. (Zahi, et al., 2000) While calcification may lead to a more extensive form of heart disease, it is less likely to lead to a heart attack.

Fatty build-up on arterial walls, though not detectable by an angiogram, can result in a small fraction of plaque breaking free. The circulating particle ultimately results in a blood clot, increasing the risk of a heart attack or stroke.

A special type of MRI, with a sensitive screening technique, is promising in regard to detecting even slight build-up in coronary arteries, including plaque without calcium deposits. This is especially praiseworthy since coronary arteries are very small and the constant movement of the heart makes a clear image difficult. The newer technique, black blood imaging, "blacks out" the blood and produces an image of just the artery. Besides being of much greater advantage in diagnosing early stage heart disease, this process is non-invasive. It is hoped that this newer more responsible means of assessing the health of coronary arteries will become a part of a routine check-up.

Coronary Bypass Surgery
Blocked arteries are not always prognosticators of an impending heart attack. The Coronary Artery Surgery Study (CASS) demonstrated that heart patients with healthy hearts but with one, two, or three of the heart vessels blocked, did amazingly well without heart surgery. The number of blockages did not alter the 1% a year death rate observed in the study groups.

A study, conducted by researchers in Iowa and published in the New England Journal of Medicine evaluated the efficiency of arteries 96% blocked, diagnosis made by angiogram. (White et al., 1984) The researchers found that arteries blocked by 96% had a greater thrust of blood than similar arteries only 40% blocked. The conclusion of the report was that the degree of closure did not correlate to the briskness of blood flow. Dr. Michael Murray, N.D., states that the most critical assessment regarding the heart's performance is how well the left ventricular pump is working, not, necessarily, the degree of closure.

It appears that aggressive procedures to open the vessels do not influence the course of the disease, except in the most advanced stages of atherosclerosis. Bypass appears only helpful when the ejection fraction is less than 40%. Many bypass procedures are performed when the ejection fraction is greater than 50%, a percentage that appears adequate for meeting the demands of circulation. Harvard Medical School researchers suggest that as many as 85% of all bypass surgeries are not necessary.

Various studies suggest that patients electing not to have the surgery appear to live as long or longer than those having surgery. The National Heart, Lung, and Blood Institute reported similar results, citing 16,000 patients who underwent bypasses. Those individuals undergoing the surgery lived no longer and with no more quality than a matched group of patients treated without surgery.

Though coronary bypass surgery can bring relief to many patients, the procedure is weighted with danger and chance. Infections, problems with blood coagulation, nerve damage, and the possibility of a heart attack or stroke are risks that must be factored into the patient's final decision.

Dr. Steven Whiting, Ph.D., states that though the odds of surviving bypass surgery have improved since the operation was first introduced, the risk of experiencing a decline in mental function following surgery has remained consistent since the 1980's. Signals of this type of decline may include difficulty following directions, mood swings and short tempers. Many doctors have down played the importance of alterations in intellectual abilities that occur in about 50% to 80% of patients following bypass surgery, believing the decline temporary. It now appears a transient display of incompetency may predict an increased risk of intellectual instability several years later.

Researchers (reporting in the New England Journal of Medicine) followed 261 bypass patients for 5 years. Enrollees in the study underwent intellectual testing before and after surgery, as well at the 6 week, 6 month and 5 year interval. Intellectual function declined by 20% to 53% considering presurgical and postsurgical mental status. The decline was 36% at 6 weeks and 24% at 6 months. Five years after surgery, 41% of the patients had experienced neurocognitive impairment. The researchers concluded that an intellectual decline in patients following heart surgery was significantly associated with diminished mental abilities 5 years post surgery. (Newman, 2001)

It should also be noted that once a bypass operation has been performed, the risk of needing additional cardiovascular procedures, i.e., either angioplasty or further surgery, increases by about 5% every year. Conversely, if coronary bypass surgery or angioplasty is appropriately advised, the procedures definitely increase long-term survival and gives symptomatic relief to about 85% of patients.

ANGIOPLASTY
In 1977, Dr. Andreas Gruentzig introduced the procedure known as balloon angioplasty, and by 1980 balloon angioplasty had become a popular cardiac option. Angioplasty is used 3 to 10 times more often in the United States than in other developed nations.

Balloon angioplasty widens coronary arteries, by inserting a specially designed catheter (a long, thin, bendable tube) with a balloon on its tip into a blocked coronary artery. After centering the tip of the catheter in the blocked area, the balloon is inflated, stretching the artery and compressing the plaque. The arteries do not fully constrict, which leaves a larger opening than before. Unfortunately, the procedure is not always yield permanent benefits. Within 6 months, a new blockage occurs in 35% to 45% of the patients undergoing angioplasty.

Any procedure using an arterial catheter may cause plaque to be dislodged or the wall of an artery to be torn. According to the PDR Family Guide Encyclopedia of Medical Care, other concerns associated with angioplasty are arterial spasms and blood clots, fluid accumulation in the lungs, as well as kidney function.

After collaborating with several universities, Ian Gilchrist, M.D., associate professor of medicine at Penn State College of Medicine and cardiologist at the Penn State Milton S. Hershey Medical Center in Philadelphia, PA, announced that 82% of complications occur within 18 hours of angioplasty. Of the patients participating in the ESPRIT (Enhanced Suppression of the Platelet Receptor glycoprotein IIB/IIIA using Integrilin Therapy) trial, most complications occurred at the time of the procedure.

The intent of the ESPRIT study was to collect information pertaining to eptifibatide, an intravenous platelet inhibitor. The medication is designed to reduce blood clots that commonly cause complications during heart procedures. As an additional perk, the study defined when the majority of the 10% of angioplasty complications occur.

Dr. Gilchrist, presenting his findings before the Scientific Sessions of the American Heart Association, announced that 178 patients (from a total of 2,064 participants) experienced a heart attack, required additional surgery, or died, and 82% of those numbers experienced the trauma within 18 hours of the procedure. Gilchrist said that despite the use of stents or antiplatelet therapy, angioplasty complications are, nonetheless, common. (Gilchrist et al., 2000) The ESPRIT study targeted the period requiring greatest watchfulness.

The original focus of the trial, i.e., establishing the worthiness and dosage of eptifibatide (Integrilin) proved a landmark study, in itself. Dr. James Tcheng, associate professor of medicine at Duke University Medical Center, reported that eptifibatide reduced the risk of major complications during angioplasty by 40% in the first 48 hours following the procedure.

About 700,000 angioplasty procedures are performed annually in the U.S. and more than 80% involve placement of stainless steel coils (stents). For years, doctors have been adding glycoprotein IIB/IIIA inhibitors to prevent the complications that can occur with stent placement. The most frequently used drug for this purposed is abciximab. Dr. Tcheng said that because abciximab is expensive, about $l, 500 a dose, many doctors do not prescribe the therapy. In fact, only 25% of patients who would be eligible for IIB/IIIA are getting the treatment, suggesting that cost is a major deterrent to prescribing this preventive treatment. Conversely, eptifibatide dosing is about $400 per patient, Tcheng said, eliminating financial barriers that could lead to changes in medical practice.

A study involving 2,400 patients undergoing coronary intervention with stenting and receiving Integrilin (eptifibatide) was halted after an almost 50% reduction in heart attack or death at 30 days analysis. Given the dramatic reduction in clinically serious outcomes, it was unanimously determined that the placebo patients should not be denied access to the therapy. Dr. Tcheng, lead investigator for the ESPRIT study said, "We can now achieve a robust reduction in death or myocardial infarction associated with intracoronary stenting coupled with the reversibility and affordability of Integrilin."

Angioplasty is not an appropriate option for everyone, however. Patients with diabetes mellitus, who are in need of revascularization, have better survival odds with coronary artery bypass grafting (CABG) compared to percutaneous transluminal coronary angioplasty (PTCA), according to study findings published in the Journal of the American College of Cardiology. (Bari Investigators, 2000) According to Dr. Katherine M. Detre, of the University of Pittsburgh in Pennsylvania, "Diabetic patients did very much worse in both respects, heart attacks and mortality, when undergoing PTCA." For treated diabetics, the 7-year survival rate was 76.4% in the CABG group and 55.7% in the PTCA group. Among non-diabetics, the survival rates were 86.4% in the CABG group and 86.8% in the PTCA group.

DOES MULTIVESSEL STENTING IMPROVE ODDS?

More than 80% of patients worldwide are treated with endovascular prostheses during coronary procedures. So great are the numbers, Dr. Martin Leon, M.D., refers to the year 2000 as the era of the "stent frenzy." A stent is a rod or threadlike device inserted within a closed or partially closed artery to allow adequate blood flow through the vessel.

According to Korean researchers, the excitement regarding stents appears justified. In fact, research suggests that some patients with coronary artery disease may be excellent candidates for multi-vessel coronary artery stenting, instead of bypass surgery. Dr. Seung-Jung Park, et al., from the University of Ulsan (Seoul), reviewed observational data, considering 200 patients with multi-vessel coronary artery disease and normal left ventricular function. Half of the patients underwent bypass surgery and the other half had multi-vessel stenting. Complete revascularization, i.e., the restoration of blood flow, was achieved in 95% of the patients who had bypass surgery and in 69% of the stent group. Over a 21-month follow-up period, survival in the two groups was similar (99% for the stent group and 97% for the bypass group) but a higher incidence of angina recurrence and target lesion revascularization occurred in the stent group. (Sang-Wook et al, 2000)

WHAT IS BRACHYTHERAPY

Because restenosis (closure) is a major concern after angioplasty, strategies that will benefit patients prone to vascular re-closure are being developed. Vascular brachytherapy, the placement of radioactive sources intra-coronary, has dramatically lowered neointimal growth patterns after angioplasty trauma. A Scripps research team in LaJolla, Calif., headed by Dr. Paul S. Teirstein, inserted a ribbon of radioactive pellets into the artery for 20 to 45 minutes to help prevent the growth of scar tissue. The 3-year follow-up showed that new blockages occurred in only 4 of the 26 patients who received the radiation treatment, compared with 14 of the 29 patients who did not. Six of the radiation-treated patients died or had heart attacks or new blockages, compared with 16 of those who did not receive the radiation.

The one-time exposure to radiation did no apparent harm to heart tissue or the artery. The Journal of the American Heart Association reported that an assessment of the procedure at the 3-year interval indicated it was both safe and effective. (Teirstein et al, 2000) Dr. Teirstein cautions, however, that until much longer follow-ups demonstrate the benefits and safety of the radiation technique, it would be premature to recommend radiation therapy for the first line of treatment for patients with clogged coronary arteries. In the interim, major hospitals are gearing for brachytherapy, as an option for patients with chronic coronary artery disease, who are subject to adhesions following cardiac procedures.

CHELATION THERAPY
Is it a bona fide alternative to heart surgery?

Chelation therapy represents, to some, a safe, effective and relatively inexpensive treatment to restore blood flow through atherosclerotic vessels. The word chelation is derived from a Greek translation, meaning "claw-like," or capable of expunging accumulated atheromatous materials.

During chelation, ethylenediaminetetraacetic acid (EDTA), a synthetic amino acid, is intravenously infused, along with other nutrients to enact the extraction process. EDTA encircles and holds elements, passing them from the body in urine. With progressive treatments, accumulated pollutants are exhumed from body stores, along with materials that encourage free radical damage and cellular breakdown.

Historically, chelation had an inception quite different from that of an anti-arteriosclerotic. EDTA's first medicinal usage appears to have been around 1941, when it was used to extract lead accumulations. A decade later, Dr. Norman Clarke, director of research at Providence Hospital in Detroit, observed that patients treated for lead poisoning with chelation therapy, had a simultaneous cessation of angina attacks. This chance beginning introduced EDTA to a few cardiovascular physicians, who were searching for alternatives to remove plaque from diseased arteries, apart from heart surgery.

Chelation therapy has had many deterrents along its' controversial pathway. Even today, the American Heart Association, after reviewing the literature in regard to chelation and arteriosclerotic heart disease, announced that the scientific evidence did not demonstrate any benefit from the therapy. The American Medical Association compared its' effectiveness to that of a sugar pill.

Dr. Robert Atkins, a complementary physician with a background in cardiology, challenges, "No matter what they say, it could save your life." Dr. Atkins, having administered chelation therapy to about 10,000 patients, considers chelation a safe alternative to heart bypass surgery or angioplasty. He declares that at the very least chelation provides short-lived differences, but typically it produces permanent reversal of existing conditions, as heart disease.

Dr. Terry Chappell, former president of ACAM, enrolled 32 physicians, who were using the standard ACAM protocol, i.e., 20 to 30 treatments of EDTA, oral nutritional supplements, and lifestyle changes, to assess the cardiovascular value of the treatment. All of the participants in the study were appropriately diagnosed with vascular disease before the therapy began. Objective testing was done before and after each treatment. The results of Dr. Chappell's investigation were that chelation therapy (in union with supplements and lifestyle intervention) was yielding positive results. The patients, 1086 out of 1241 or 88%, reported subjective betterment; their doctors reported "significant clinical improvement."

The therapeutic reputation of chelation therapy has pyramided among certain cardiac physicians. Arteriosclerosis/atherosclerosis, angina pectoris, hypertension, transient ischemic attacks, circulatory disease, hemochromatosis, and Type II diabetes, are among the heart-related conditions currently treatable with chelation therapy. (The purpose of chelation in diabetes is to remove calcium deposits, normalize cholesterol levels, and decrease free radical activity.)

Dr. Morton Walker, author of the Chelation Way, reminds us that an aspirin is less than one-third as safe as intravenous EDTA. The LD-50 of aspirin is only 558 mg per kg in humans, while EDTA's LD-50 is 2000 mg per kg. NOTE: LD-50 stands for the pharmaceutical term "lethal dose 50," the dose of a substance that is fatal to 50% of test animals. Dr. Walker, a staunch advocate of chelation therapy, believes that the danger of death from bypass surgery is about 6000 times greater than from chelation therapy.

The success of chelation therapy appears directly related to the refusion of minerals withdrawn during the extraction process. A physician trained in autonomic balancing appears essential to the success or failure of the process.

Some physicians believe that, unless the patient is in immediate danger or great discomfort, oral chelation is an option to intravenous chelation therapy. Oral chelation takes longer to bestow equal benefits, i.e., reducing the damaging effects of free radicals and flushing out arterial plaque, but in time the body is cleansed and blood flow to all body regions appears improved. Drs. Edward Olszewer and James Carter reported that 75% of 2870 patients receiving oral EDTA chelation therapy experienced a marked improvement in geriatric symptomatology of vascular origin.

Chelators commonly complexed into a single oral formulary include: L-glutathione, L-carnitine, L-methionine, garlic, hawthorn, and orally administered EDTA.

CORONARY GENE THERAPY

Coronary gene therapy is another alternative to either angioplasty or coronary artery by-pass surgery, for high-risk patients. Gene therapy increases the options of individuals who have failed drug treatment and appear poor candidates for aggressive surgical procedures. A battery of tests confirms the acceptability of a patient wishing to be enrolled in the gene program.

During coronary gene therapy, x-ray imaging allows the gene for the human vascular endothelial growth factor, VEGF2, to be delivered, via a catheter inserted through a puncture in the inguinal (groin) region, to the heart. A needle is advanced out of the catheter and used to inject DNA into the inner wall of the heart, a sequence that produces the vascular endothelial growth factor and stimulates the growth of new blood vessels. Data reported in the New York Times, August 29, 1999 suggests that VEGF2 is capable of invoking the growth of new blood vessels, with some individuals experiencing re-growth in about 60% of the area previously occluded. Though the process is constantly being advanced and refined, many patients have, successfully, undergone the treatment since 1998.

Two concerns researchers have had about gene therapy are that the blood vessel growth factors could nourish the blood supply of undetected cancers and/or cause damaging overgrowth of vessels in tissues such as the retina of the eye. Dr. Timothy Henry, of Hennepin County Medical Center in Minneapolis, reported that among 106 patients enrolled in a VEGF trial, four patients in the placebo group had developed cancer compared with one patient in the low-dose VEGF group and none in the high dose group. Overall mortality was 3% in the placebo group, 6% in the low-dose VEGF group and 0% in the high dose group. The incidence of myocardial infarction was 3% in the placebo patients, 0% in the low-dose group and 6% in the high-dose VEGF group.

Currently, there appears no retinal damage in diabetic patients, who have undergone the procedure. These results are preliminary and inconclusive, but early assessments deem VEGF therapy a burgeoning alternative to either bypass surgery or angioplasty for coronary/vascular disease. For more information concerning coronary gene therapy contact St. Elizabeth's Medical Center of Boston at 1-888-311-GENE.

EVIDENCE THAT CARDIAC CELLS DIVIDE AFTER A HEART ATTACK

Most tissues and organs are equipped to deal with injury more efficiently than the heart. For example, the mending of broken bones and renewal of injured skin is so mundane they are taken for granted. Until recently, it was thought that myocytes (muscle cells) of the adult heart were incapable of self-renewal, i.e., once damaged, always damaged, without the hope of regeneration. Reports published in the NEJM indicate this may not be the case. (Beltrami et al, 2001)

Researchers looked at heart muscle cells from the hearts of 13 deceased patients, 4 to 12 days after their heart attack. These findings were compared to the hearts of 10 patients who had not died of cardiovascular disease. Samples of heart tissue were taken from the area near the site of the heart attack and from a more distant site from the damage. Scientists found that the number of myocytes multiplying in diseased hearts was 70 times higher in the border zone and 24 times higher in the remote area. The presence of cell division in the non-diseased portion of the heart suggests a continuous turnover of cells during the life span of the organism. It is now thought that cardiac muscle cells can reproduce, advancing the premise that this process may be a component of the growth reserve of the human heart. The ramifications of this research allows for the prospect of replacing damaged myocardium by stimulating the heart's own repair capacity.

The focus of current study is to identify the premature stem cells that give rise to multiplying myocytes, encouraging growth and repair in damaged areas. If, indeed, cardiac stem cells exist, the challenge will be to persuade these cells to move to regions of tissue damage to facilitate repair and reduce heart failure.

While these reports raise hopes for employing the body's capacity for self-renewal, the excitement must be tempered by the scope of the obstacles. While the hurdles to overcome are sizable, the current studies have advanced understanding by challenging dogma. Showing that cardiac muscles are capable of regeneration opens up remarkable pathways for healing an ailing heart.

SUMMARY
Review Of The Supplements For Preventive and Therapeutic Use

A brief reminder of the supplements introduced in the material follows. Obviously, all of the supplements are not applicable to any one individual. The selection of supplements should be made with a slant toward prevention and clinically confirmed weaknesses. Complexes of nutrients are available, lessening the quantity of individual supplements required in a comprehensive program.

The + in the margin (to the left of the supplement in the recall section) indicates the supplement has both preventive and therapeutic value in regard to heart disease. Individuals who are without clinically confirmed weaknesses will profit from a program centered upon prevention and should seek out areas coded with a +.

Individuals who have established heart disease should take solace in the quantity of the therapeutics presented and the documentation supporting their value. The supplement's mode of operation (appearing immediately below the introduction of the product in the Therapeutic Section) will be extremely helpful to a reader who has multiple cardiovascular risks.

Though natural medicine conveys tremendous possibilities for a heart patient, these options should not be charted without the help of a trained health care professional. Select a physician who respects all disciplines, i.e., an individual who understands that natural medicine can often circumvent a drug, delivering like, but safer, results. (Though the window of safety is, generally, judged wider when comparing natural medicine to drug therapy, mega dosages can change the disposition of a supplement, pressing it in some incidences to the rank of a drug; therefore, close professional supervision is essential to accomplish intent with safety.)

One heart, one life demands the best of all medical offerings; this means not structuring your program alone, but rather with the assistance of a broadly focused physician. Note: pregnant women should always seek the counsel of a qualified practitioner who understands the interactions of the supplement upon the fetus.

RECALL THAT:

	+ Alpha lipoic acid is an antioxidant, antidiabetic, inhibits protein glycation, beneficial in congestive heart failure and stroke prevention, hypercholesterolemia and hypertension. Suggested therapeutic dosage: 500 to 1000 mg daily. Preventive dose: 250 mg-500/day.
	Angelica (Angelica archangelica) is an anti-anginal, antiinflammatory, calcium antagonist, ACE inhibitor, and diuretic. Dosage:15 to 30 drops one to three times a day.
	L-arginine dilates blood vessels and reduces the atherogenesity of atherogenic foods. Mimics the actions of nitroglycerine. Suggested dose: 2 gram of L-arginine before bedtime.
	Artichoke (Cynara scolymus) lowers total serum cholesterol and triglycerides. Recommended dose: one capsule three times per day, containing 300 mg of artichoke standardized to contain 13-18% caffeoylquinic acid.
	+ Aspirin, one tablet (81 mg a day with a heavy meal), reduces fibrinogen levels, platelet aggregation, C-reactive protein, and inflammatory conditions. (Higher doses may be required to impact newer risk factors, as CRP.) Low dose aspirin is usually begun at about 50 years of age, according to the American College of Chest Physicians, if no physical condition precludes its usage.
	Bromelain is an anti-inflammatory, a hypotensive, reduces fibrinogen levels and atrial fibrillation, lessens risk of blood clots, relieves angina, particularly beneficial to smokers. Suggested dosage: 750 mg used 3 times per day on an empty stomach.
	Bugleweed (Lycopus virginicus) has diuretic and digitalic properties. Use 30 to 40 drops in a little water three to four times a day.
	Cactus (Selenicereus grandiflorus) lessens attacks of tachycardia, anxiety, and arrhythmias, faintness, dyspnea, valvular murmurs, angina, and endocarditis. Suggested dosage: 30 to 40 drop two to four times a day.
	+ Calcium reduces blood pressure, acts as an antiarrhythmic, reduces iron overload, and strengthens the bone around the gingiva (important in periodontal disease). Dosage: 1.5 gram daily. Preventive dosage: the body requires between 1000 and 2000 mg of elemental calcium/day; factor amount of dietary calcium (that obtained from foodstuffs) into amount required through supplementation.
	+ L-carnitine is an energizer and hypolipidemic, aids weight loss, and improves circulation, beneficial in angina and diabetic management. Most clinical trials use 1,500 to 3,000 mg daily. Preventive dosage: 600-1500 mg/day.
	Carnosine acts as an antioxidant, reduces glycation and the likelihood of a stroke. Suggested dosage: 1000 to 1500 mg/day. (Not recommended during pregnancy or lactation.)
	+ Chondroitin Sulfate is an anti-inflammatory, antioxidant, inhibits LDL oxidation. Suggested daily dose: one to three 400-mg tablets. Preventive dosage: 400 mg/day.
	+ Chromium, 300 to 400 mcg in divided doses/day, modulates blood glucose levels, decreases cholesterol, helpful in weight management. Preventive dosage: 200 mcg/day.
	+ Coenzyme Q10 reduces angina attacks, arrhythmias, congestive heart failure, periodontal disease, and heart valve irregularities, lowers blood pressure, is protective to smokers, and supplies energy to the heart. Dosage suggestions: 30-400 mg/day, depending upon the amount of cardiac support required. (Fats enhance absorption; higher doses require physician supervision.) Preventive dosage: 30 mg/day, if young and heart healthy.
	Conjugated linoleic acid (CLA) aids in weight loss and utilization of beneficial fats, reduces cholesterol and triglycerides, increases insulin sensitivity, has antioxidant activity. Suggested dosage: three to six 500-mg capsules used daily, in divided doses.
	Curcumin is an anti-inflammatory, blood thinner, hypocholesterolemic, protective to smokers, inhibits platelet aggregation. Recommended dosage: 900 mg two times daily.
	+ DHEA and nettle leaf extract suppress activity of pro-inflammatory cytokines (interleukin-1B, interleukin-6, and tumor necrosis factor alpha). Suggested DHEA dosage: 15 mg to 75 mg day, taken early in the day. (50 mg is a typical daily dose). Read about DHEA in the Therapeutic Section for caveats. Use 300 mg of nettle leaf extract three times/day. Preventive medicine: determine baseline DHEA levels and if indicated, dose with 50 mg/day.
	+ Essential fatty acids modulate blood lipids and body weight, improve heart function, lessen risk of restenosis and strokes, thin the blood, inhibit platelet clumping, have hypotensive and anti-inflammatory activity, reduce fibrinogen, homocysteine, and C-reactive protein levels, improve insulin sensitivity. Perilla oil, 1,000 mg capsules, provides 550-620 mg of alpha-linolenic a precursor to EPA and DHA. Use 3-6 capsules per day. Flaxseed oil, 1000 mg softgels, is a rich source of omega-3 fatty acids. Use one to six softgels per day. Blends of fish oils are available supplying varying amounts of EPA and DHA. Evening primrose oil is a source of gamma-linolenic acid (GLA). Use one to two 1300-mg evening primrose softgels daily. Borage oil, also, supplies GLA. Use 1-2 softgels (1300 mg) daily as a preventative and up to 5 softgels per day as a therapeutic dose.
	+ Fiber assists in weight management, is a hypolipidemic and antidiabetic. Daily dosage: begin with only one teaspoon until the system adjusts to the new material; increase to one teaspoon three times per day. It is essential to drink additional water when fiber is added to the diet.
	+ Garlic acts as a hypotensive, decreases fibrinogen, lowers cholesterol, protects against LDL oxidation, inhibits platelet aggregation, thins the blood, modestly lowers blood glucose levels, reduces damage associated with iron overload and the incidence of cardiac arrhythmias. Dosage suggestions: the equivalency of 4,000 mg of fresh garlic daily.
	Ginger reduces cholesterol, thins the blood, reduces the risk of blood clots, and has anti-inflammatory properties. Suggested dosage: one to two 300 mg capsules, one to three times per day.
	Ginkgo biloba improves circulation and memory, reduces platelet aggregation, arrhythmias, and fibrinogen levels, has antioxidant activity, prevents capillary fragility, lessens angina attacks, dyspnea, intermittent claudication, decreases the area in the brain plundered by a stroke. Suggested dosage: 120-240 mg daily.
	Grapefruit pectin is an effective hypocholesterolemic. If using the powder, begin with less than one scoop/day; gradually increase to 2-3 scoops. If using tablets, use 1-3 1000 mg/day with meals.
	+ Green tea acts as an anti-thrombotic, antioxidant, hypotensive, anti-inflammatory, and antagonist to iron excess. Drink several cups a day or use 4-10 supplemental capsules/day. Preventive: enjoy several cups /day.
	Gugulipid lowers cholesterol and triglycerides, regresses plaque formation, opposes platelet aggregation, and has fibrinolytic activity. Suggested dosage: 500 mg three times per day.
	Hawthorn berry (Crataegus oxyacantha) is an antioxidant, antihypertensive, diuretic, aid to weight loss, reduces hypoxia and premature ventricular contractions, lowers cholesterol, beneficial in congestive heart failure, acts as a vasodilator, ACE inhibitor, and calcium antagonist, increases exercise tolerance. Daily dosages: 250 to 900 mg/day.
	+ The following daily supplements (used alone or in combination) are effective in lowering homocysteine levels: 500 to 9000 mg of TMG, 800 to 5000 mcg of folic acid, 1000 to 3000 mcg of vitamin B12, 250 to 3000 mg of choline, 250 to 1000 mg of inositol, 30 to 90 mg of zinc, 200 to 800 mg of SAMe, and 100 to 500 mg of B6. (Use SAMe with other cofactors listed.)
	+ Magnesium reduces blood pressure, acts as a calcium channel blocker and antiarrhythmic, blocks sympathetic nervous system, beneficial in mitral valve prolapse. Use up to 1500 mg in divided doses throughout the day. Preventive dosage: 900 mg/day.
	Niacin lowers Lp(a) and fibrinogen, normalizes cholesterol levels. One to three gram of niacin per day may be needed to lower cholesterol. Lower doses of niacin may be effective if taken in union with chromium. If high dose niacin is to be used, liver function tests should be performed regularly.
	Olive leaf extract is hypotensive, anti-diabetic, vasodilating, helpful in some types of arrhythmias, protective against LDL oxidation. Use one to two 500 mg capsules three times a day with meals.
	Administering 300 mg of pantethine three times per day, typically, results in a significant improvement in lipid parameters.
	The University of Chicago Medical Center announced that foods containing phthalides appear remarkable in lowering blood pressure. Carrots, celery, parsley, parsnips, and cilantro (1/4 pound) lowered blood pressure 30% in one week.
	Policocosanol is hypocholesterolemic, protects LDL cholesterol against oxidation, inhibits thromboxane and the proliferation of vascular cells, discourages blood clot formation, has anti-platelet aggregating activity, increases exercise tolerance. Suggested dose: some individuals will need only 5-10 mg to maintain healthy levels of cholesterol; others will require 20 mg a day.
	Polyenylphosphatidylcholine (PPC) (administered in two 900 mg capsules a day) lowers blood lipids, reduces angina attacks, and improves exercise tolerance.
	+ Potassium reduces blood pressure, maintains fluid balance, and makes stronger the parasympathetic nervous system. Potassium intake should be between 1.9 grams and 5.6 grams/day. If diet does not provide adequate amounts of potassium, supplementation becomes essential.
	+ Proanthocyanidins are antioxidants and weak ACE inhibitors, protects endothelium against white blood cell adherence, reduces blood cholesterol and existing cholesterol deposits, beneficial to smokers. Daily dose: 50 mg is considered a preventive dose, 150-300 mg a therapeutic dose.
	+ Selenium is beneficial in cardiomyopathy, ventricular tachycardia, hyperlipidemia, congestive heart failure, and diabetes. Dosage: 200 to 300 mcg per day. Preventive dosage: 200 mcg/day.
	Soybeans boost thyroid performance and reduce blood lipids. Suggested dosage: 2 to 4 tablespoons daily.
	+ Taurine is hypotensive, quiets sympathetic nervous system, beneficial in congestive heart failure and arrhythmias, has blood thinning and diuretic properties. Suggested dosage: 1500 to 4000 mg in divided dosages daily. Preventive dosage: 500 mg/day.
	Testosterone modulates cholesterol, dilates blood vessels, improves circulation, lessens angina attacks, and reduces blood pressure. The objective is to restore testosterone levels to that of a healthy 21-year old.
	Thiamine (vitamin B1) reduces cardiac arrhythmias, palpitations, congestive heart failure, and elevated venous pressure. Some patients may realize benefit from 200 to 250 mg of thiamine per day; refractory cardiac arrhythmias may require 500 to 1000 mg per day.
	+ Tocotrienols inhibit platelet clumping, reduce cholesterol, have antioxidant potential. Suggested daily dosage: 100 IU mixed tocopherols and 100 IU tocotrienols if healthy and young, without a family history of heart disease; 200 IU of mixed tocopherols and 200 IU of tocotrienols for young adults with some cardiac risk factors or healthy people without risk factors up to 50 years of age; 400 IU of mixed tocopherols and 400 IU of tocotrienols for people who have a personal or family history of chronic disease. This dosage includes those who are elderly or stressed, and eat a poor diet.
	+ Vitamin A/beta carotene, 20,000 IU/day and 25,000 IU/day (respectively) modulates fibrinogen levels. Preventive dose 10,000 IU beta-carotene and 5,000 IU vitamin A.
	+ Vitamin C strengthens and dilates blood vessels, promotes gingival healing, lowers blood pressure, reduces fibrinogen, Lp(a), C-reactive protein, and atheromatous plaque, lessens damage inflicted by smoking, has diuretic activity. Suggested preventive and therapeutic dose: 6 gram daily, in divided dosages.
	+ Vitamin E assists in preventing plaque formation, protects LDL from oxidation, strengthens blood vessels, prevents blood viscosity, beneficial in atrial fibrillation, reduces the incidence of ventricular fibrillation, reduces C-reactive protein, is considered an anti-diabetic nutrient. Suggested preventive and therapeutic dosage: 400 to 1200 IU daily.
	+ Vitamin K prevents calcium from tying up in arteries, reduces inflammatory process, and risk of a blood clot. Suggested daily dose: 10 mg.
	+ Zinc, 30 to 60 mg/day, may increase testosterone levels, is beneficial to diabetics and those overweight. Because high doses of zinc can increase blood glucose levels, prediabetics and diabetics should use no more than 15mg/day, the RDA. Preventive dose for a non-diabetic: 30 mg/day.
	It would be helpful for a cardiac patient to consult a physician trained in autonomic balancing. Drug and nutrient cohesiveness eliminates mixed messages being delivered to the heart and vascular system.
	Laboratory testing to determine values of traditional and newer risk factors are valuable to all age groups. Testing becomes part an ongoing prevention plan for the healthy and a means of monitoring progress for those with established cardiovascular disease. Be sure that you are being tested using the latest in screening tools, i.e., technology capable of measuring the smaller, denser LDL particles (the form most susceptible to oxidation) and high-sensitivity CRP screening.
	There are many ways that you can improve your health odds. Become a participant in your health care program. Learn the medical terminology, request specific tests, suggest and reject various medicines
	Recall that the heart beats best when the host is peaceful and less stressful. Communicate a spirit of contentment and fearlessness to your inner self. Unresolved stress cannot be justified, when you realize the price of the aggravation may be life threatening.

PRODUCT AVAILABILITY: Alpha lipoic acid, L-arginine, Artichoke Leaf Extract, Aspirin, Beta Carotene, Bromelain, Calcium, L-Carnitine, Carnosine, Choline, Chondroitin Sulfate, Chromium, CoQ10, Conjugated Linoleic Acid, Curcumin, DHEA, Essential Fatty Acids, Fiber, Folic Acid, Garlic, Ginkgo biloba, Grape Seed-Skin Extract, Magnesium, Olive Leaf Extract, Policosanol, SAMe, Selenium, Soy Protein, Taurine, TMG, Tocotrienols, Vitamins A, B1, B3, B6, B12, C, E, and zinc are available by calling (800) 544-4440 or by ordering on-line.