Atherosclerosis and cardiovascular disease take a huge toll on our society. More than 81 million Americans suffer from some form of cardiovascular disease, making it the leading cause of death in the country. As of 2006, cardiovascular disease was responsible for at least one in every 2.9 deaths in the United States (American Heart Association: Heart Disease and Stroke Statistics 2010).
Despite the fact that cardiovascular disease is the single most deadly disease in the United States, most individuals, including most mainstream physicians, have a flawed fundamental understanding of the disease. The fact is, long before any symptoms are clinically evident, vascular disease begins as a malfunction of specialized cells that line our arteries. These cells, called endothelial cells, are the key to atherosclerosis and underlying endothelial dysfunction is the central feature of this dreaded disease.
Not every person who suffers from atherosclerosis presents with the risk factors commonly associated with the condition, such as elevated cholesterol, but every single person with atherosclerosis has endothelial dysfunction. Aging humans are faced with an onslaught of atherogenic risk factors that, over time, contribute to endothelial dysfunction and the development of atherosclerosis.
Maturing individuals must address all of the underlying factors that contribute to endothelial dysfunction if they are striving to protect themselves from the ravages of vascular disease. Regrettably, mainstream medicine has failed to identify and correct all of the cardiovascular disease risk factors. This means that people wishing to stave off atherosclerosis must take matters into their own hands to ensure that all underlying causes are effectively neutralized.
In the antiquated view of mainstream medicine, blood vessels have been thought of as stiff pipes that gradually become clogged with excess cholesterol circulating in the bloodstream. The solution that physicians recommend most often is cholesterol-lowering drugs, which target only a very small number of the numerous factors that contribute to cardiovascular disease.
Conventional medicine’s preferred method of reestablishing blood flow in clogged vessels is through surgery (coronary artery bypass graft surgery) or by insertion of catheters bearing tiny balloons that crush the plaque deposits against the arterial walls (angioplasty), followed by the implantation of tiny mesh tubes (stents) to keep the blood vessels open. However, the grafts used to reestablish blood flow often develop plaque deposits themselves. The same was true for balloon angioplasty; in their early years, up to half of all angioplasty procedures “failed” when the arteries gradually closed again. Even today, with the use of improved stents, the failure rate is considerable and many people have to undergo repeat angioplasty or even surgery.
Endothelial Dysfunction: The Underlying Cause of All Vascular Diseases
The cause and progression of vascular disease is intimately related to the health of the inner arterial wall. Blood vessels are composed of three layers. The outer layer is mostly connective tissue and provides structure to the layers beneath. The middle layer is smooth muscle; it contracts and dilates to control blood flow and maintain blood pressure. The inner lining consists of a thin layer of endothelial cells (the endothelium), which provides a smooth, protective surface. Endothelial cells prevent toxic, blood-borne substances from penetrating the smooth muscle of the blood vessel.
However, as we age, a barrage of atherogenic factors, if left unchecked, damages the delicate endothelial cells. This damage leads to endothelial dysfunction and ultimately allows lipids and toxins to penetrate the endothelial layer and enter the smooth muscle cells. This results in the initiation of an oxidative and inflammatory cascade that culminates in the development of plaque deposits. Subsequently, these plaques begin to calcify and, over time, become prone to rupture. If a plaque deposit ruptures, the result is oftentimes a deadly blood clot.
If people do not take steps to correct the endothelial dysfunction occurring in their aging bodies, the consequence will be a worsening of the epidemic of arterial disease that currently kills 35% of Americans and 30% of all people worldwide (American Heart Association: Heart Disease and Stroke Statistics 2010). Sadly, mainstream medicine continuously fails patients by prescribing drugs that address only a very small number of risk factors that contribute to the pathogenesis of vascular disease.
Numerous factors that directly contribute to endothelial dysfunction have been identified and aging individuals can easily assess their risk for vascular disease through blood testing. The results of these blood tests can then be used to develop targeted intervention strategies to modify levels of risk factors that do not fall within an optimal range. Atherogenic factors that all aging individuals must be aware of include:
- Elevated LDL cholesterol. LDL is dangerous because it can penetrate the endothelial wall and contribute to the creation foam cells, which form the core of a plaque deposit. Oxidized LDL cholesterol (LDL that has been exposed to free radicals) within the endothelium also triggers an inflammatory process that accelerates vascular disease. Life Extension recommends keeping LDL cholesterol levels below 80 mg/dL.
- Low HDL cholesterol. HDL protects against vascular disease by transporting cholesterol from the blood vessel wall back to the liver for disposal through a process known as reverse cholesterol transport. If HDL levels are low, then reverse cholesterol transport becomes inefficient, allowing for increased accumulation of cholesterol in the vessel wall. HDL levels of at least 50-60 mg/dL are recommended for optimal vascular protection.
- Elevated triglycerides. Triglycerides interact with LDL cholesterol to form a particularly dangerous sub-type of LDL known as small-dense LDL. Small-dense LDL particles penetrate the endothelial layer and contribute to plaque formation much more efficiently than larger, more buoyant LDL particles. Life Extension recommends keeping fasting triglycerides below 80 mg/dL to limit the formation of small-dense LDL particles.
- Oxidized LDL. The oxidation of LDL results in severe vascular damage. Thousands of studies now reveal how oxidized LDL contributes to the entire atherogenic process from start to finish. Commercial blood tests are not yet available at affordable prices to measure oxidized LDL. Aging individuals should assume their endogenous antioxidant levels (superoxide dismutase, catalase, and glutathione) are being depleted and that the oxidation of their LDL is progressively worsening (Matsuura, 2008). Many of the nutrient suggestions in this protocol afford considerable protection against LDL oxidation.
- Hypertension. High blood pressure is known to aggravate endothelial dysfunction and leading researchers have identified the endothelium as an “end organ” for damage caused by high blood pressure. Life Extension suggests a target optimal blood pressure of 115/75 mmHg (or lower).
- Elevated C-reactive protein. Inflammation is central to the endothelial dysfunction that underlies vascular disease. An effective way to measure inflammation is through a high-sensitivity C-reactive protein (CRP) blood test. Studies have shown that higher levels of CRP are associated with increased risk of stroke, heart attack, and peripheral vascular disease (Rifai N 2001; Rifai N et al 2001). Stroke patients with the highest CRP levels are two to three times more likely to die or experience a new vascular event within a year than are patients with the lowest levels (Di Napoli M et al 2001).
- Elevated Lp-PLA2. Like CRP, Lp-PLA2 is a marker of inflammation. However, Lp-PLA2 is a much more specific measure of vascular inflammation than CRP. Lp-PLA2 is an enzyme secreted by inflamed vascular plaque, thus the quantity of it in circulation correlates with the amount of inflamed plaque in the blood vessels. Levels of Lp-PLA2 above 200 ng/mL are indicative of heightened levels of vascular plaque buildup.
- Elevated omega-6:omega-3 ratio. High levels of pro-inflammatory omega-6 fatty acids relative to anti-inflammatory omega-3 fatty acids create an environment that fosters inflammation and contributes to vascular disease. It has been shown that lowering the omega-6:omega-3 ratio significantly decreases atherosclerotic lesion size and reduces numerous measures of inflammation (Wan, 2010). Life Extension recommends maintaining a blood omega-6:omega-3 ratio of less than 4:1.
- Elevated glucose. High circulating levels of blood glucose (and insulin) cause microvascular damage that accelerates the atherogenic process, partly by contributing to endothelial dysfunction (Beckman JA et al 2002). It has been shown that a fasting blood glucose level of greater than 85 mg/dL significantly increases risk of cardiovascular related mortality (Bjørnholt, 1999). Life Extension suggests keeping fasting blood glucose levels below 86 mg/dL.
- Excess insulin. As we age, we lose our ability to utilize insulin to effectively drive blood glucose into energy-producing cells. As glucose levels rise in the blood, the pancreas compensates by producing more insulin. As “insulin resistance” worsens, even more insulin is secreted in attempt to restore glucose control. Excess insulin is associated with a significantly greater risk of heart disease (Bonora, 2007). Life Extension suggests keeping fasting insulin below 5 mcIU/mL.
- Elevated homocysteine. High homocysteine levels damage endothelial cells and contribute to the initial pathogenesis vascular disease (Riba R et al 2004). Homocysteine levels are associated with risk of heart disease (Haynes WG 2002; Guilland JC et al 2003). To keep homocysteine-induced endothelial damage to a minimum, levels of homocysteine should be kept below 7-8 µmol/L.
- Elevated fibrinogen. When a blood clot forms, fibrinogen is converted to fibrin, which forms the structural matrix of a blood clot (Koenig W 1999). Fibrinogen also facilitates platelet adherence to endothelial cells (Massberg S et al 1999). People with high levels of fibrinogen are more than twice as likely to die of a heart attack or stroke as people with normal fibrinogen levels (Wilhelmsen L et al 1984; Packard CJ et al 2000). In a review which included data for over 154,000 patients, every 100 mg/dL increase in fibrinogen levels was associated with a significantly increased risk of developing coronary heart disease, stroke, and with vascular related mortality. In one study, those patients with the lowest one-third fibrinogen levels (mean 236 mg/dL) were much less likely to suffer a stroke, develop cardiovascular disease, or die of other vascular related causes when compared to those with the highest one-third fibrinogen levels (mean 374 mg/dL) (Danesh, 2005). This risk goes up even more in the presence of hypertension (Bots ML et al 2002). Fibrinogen levels should be kept between 295 to 369 mg/dl.
- Insufficient vitamin D. Vitamin D protects against vascular disease via several different mechanisms, including reducing chronic inflammatory reactions that contribute to the pathology of the disease. It has been shown that low vitamin D levels are associated with increased cardiovascular mortality (Dobnig, 2008). Life Extension suggests maintaining a 25-hydroxy vitamin D blood level of 50 – 80 ng/mL.
- Insufficient vitamin K. Vitamin K is essential for regulating proteins in the body that direct calcium to the bones and keep it out of the arterial wall. Low vitamin K status predisposes aging humans to vascular calcification (Adams, 2005; Beulens, 2009; Schurgers, 2007), chronic inflammation (Morishita, 2008), and sharply higher heart attack risks (Geleijnse, 2004). Vitamin K blood tests assess levels of vitamin K to maintain healthy coagulation, but at this time are not used to identify optimal levels to reduce heart attack risk. However, there is a substantial amount of evidence that suggests that supplementation with vitamin K (as K1, MK-4 and MK-7) easily corrects the vitamin K deficits that are so common among Americans today (Nouso, 2005; Lin, 2005; Braam, 2004; Berkner, 2004; Gunther, 2004).
- Low testosterone and excess estrogen (in men). Numerous studies link low testosterone (and excess estradiol) with increased heart attack and stroke risk (Wranicz, 2005; Abbott, 2007; Tivesten, 2006; Dunajska, 2004). Testosterone is intimately involved in the reverse cholesterol transport process, which removes cholesterol from the arterial wall by HDL. Excess estrogen is linked with higher C-reactive protein and a greater propensity for abnormal blood clots to form in arteries, causing a sudden heart attack or stroke (Stork, 2008; Zegura, 2006). Men should keep their free testosterone in a range of 20 – 25 pg/mL and their estradiol levels between 20 – 30 pg/mL (Jankowska, 2009).
- Insufficient CoQ10. Supplemental CoQ10 alters the pathology of vascular diseases and has the potential for prevention of vascular disease through the inhibition of LDL cholesterol oxidation and by the maintenance of optimal cellular and mitochondrial function throughout the ravages of time and internal and external stresses. The attainment of higher blood levels of CoQ10 (> 3.5 micrograms/mL) with the use of higher doses of CoQ10 appears to enhance both the magnitude and rate of clinical improvement (Langsjoen, 1999).
- Nitric oxide deficit. Nitric oxide is an important messenger molecule required for healthy cardiovascular function. Nitric oxide enables blood vessels to expand and contract with youthful elasticity and is vital to maintaining the structural integrity of the endothelium, thus protecting against vascular disease. Even when all other risk factors are controlled for, the age-related decline in endothelial nitric oxide too often causes accelerated vascular disease unless corrective measures are taken. Commercial blood tests are not yet available at affordable prices to assess nitric oxide status. Aging individuals should assume they are developing a nitric oxide deficit in their inner arterial wall (the endothelium) and follow simple steps outlined in this protocol to protect themselves (Yavuz, 2004; Cai, 2000; Nitenberg, 2006).