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Cerebral Vascular Disease
Tissue Plasminogen Activator
The FDA approved the use of a tissue plasminogen activator (t-PA) in June 1996 to treat strokes. t-PA had already been approved to dissolve clots that occur in the coronary arteries (which cause an acute heart attack), but the FDA has delayed approving t-PA to treat ischemic stroke for many years. Millions of cases of death and permanent paralysis occurred because of the FDA's delay in approving t-PA in treating stroke caused by abnormal blood clotting in the brain's arteries. Physicians affiliated with the Life Extension Foundation were using t-PA in emergency rooms to treat ischemic stroke years before the FDA gave its official seal of approval.
t-PA (sold under the brand name Activase) should be administered immediately (or within 3 hours) after a stroke to dissolve the clot that is preventing blood from reaching a portion of the brain. t-PA is a natural clot-dissolving substance produced by the body and can literally "blow open" the blood clot in the brain that is causing the acute ischemic brain damage characteristic of a stroke. However, it is crucial that the attending physician review all of the inclusion and exclusion criteria associated with the use of t-PA in advance of its administration. Examples of exclusion criteria making t-PA absolutely contraindicated include an intracranial mass or hemorrhage; very low or high glucose; a previous stroke or head trauma within the last 3 months; current use of anticoagulant drugs; a seizure at the onset of the stroke; major surgery within the last 2 weeks; low platelets; gastrointestinal hemorrhage within the last 3 weeks; blood pressure greater than 185/110; or a previously known cerebral aneurysm (Adams et al. 1996).
One study has shown that 30% more stroke victims were able to regain full use of their faculties after receiving t-PA. In this study 45% of the stroke victims had a good result, defined as "complete regression or slight neurological sequelae." The subgroups with poor prognosis outcomes in three parameters showed a good outcome in 30% of those patients with each of these characteristics (Trouillas et al. 1998). Even today, patients may encounter extreme resistance from emergency room physicians who are reluctant to administer it (Alberts 1998), even if a patient's life is at stake. In some cases, surgery may be required to remove any blockage of blood vessels going to the brain because it is important to get the blood circulating to the brain.
While t-PA can dissolve the blood clot that causes a blood vessel blockage, there are other complications that occur during ischemic stroke that have to be addressed if permanent brain damage is to be prevented. Any interruption in blood flow causes an oxygen imbalance that results in massive free-radical damage. It is critically important to have antioxidants in your bloodstream when t-PA is administered to reduce the free-radical damage that will occur when blood flow is restored (Ozmen et al. 1999).
Heparin
Heparin is a natural polysaccharide normally found in mast cells. Heparin increases the activity of antithrombin III, preventing the conversion of fibrinogen to fibrin. Heparin must be administered parenterally (by IV) because it is not absorbed in the GI tract. Because of this, heparin may be used in acute care situations, but not usually in stroke prevention.
Silent Strokes
Debilitating strokes depicted on television shows or in movies have severe symptoms. Most strokes, however, are not as dramatic. Often the symptoms are minor and transient and may be ignored or dismissed as unimportant. Over time these silent strokes lead to memory loss and other neurological problems. According to one study, by the time people reach their 70s, one in three has a silent stroke every year (Leary 2001).
Of particular concern to stroke victims is that silent strokes occur frequently, causing neurological damage days or weeks after the initial crisis. A 2001 study found that one fourth of stroke survivors had at least one silent stroke during the 2 years following their initial stroke (Corea et al. 2001).
The Underlying Causes
We usually consider a heart attack a life-or-death health event. Strokes have been given less attention, but the realization that stroke is an acute event has now led to stroke being referred to as a brain attack. Thrombotic strokes are a major cause of brain attacks and are caused in part by atherosclerosis, hypertension, and procedures that cause abnormal arterial blood clot formation (thrombosis), such as atrial fibrillation and heart valve replacement.
As with almost all cardiovascular disease, strokes are generally the result of several underlying diseases which result in stopping or reducing the flow of blood to the brain.
The majority of strokes occur when a blood clot blocks the flow of oxygenated blood to a portion of the brain. This type of stroke, caused by a blood clot blocking or "plugging" a blood vessel, is called ischemic stroke. An ischemic stroke can be caused by a blood clot that forms inside the artery of the brain (a thrombotic stroke) or by a clot that forms somewhere else in the body and travels to the brain (an embolic stroke). In healthy individuals, blood clotting is beneficial. When you are bleeding from a wound, blood clots work to stop the bleeding. In the case of ischemic stroke, abnormal blood clotting blocks large as well as small arteries in the brain, cutting off blood flow and resulting in a clinical diagnosis of ischemic, thrombotic, or embolic stroke.
Ischemic strokes account for 80% of all strokes and occur as either an embolic or thrombotic stroke. Thrombotic strokes represent 52% of all ischemic strokes. Thrombotic strokes are caused by unhealthy blood vessels becoming clogged with a buildup of fatty deposits, calcium, and blood-clotting factors such as fibrinogen and cholesterol. We generally refer to this as atherosclerotic disease. Simplistically, what happens with a thrombotic stroke is that our bodies regard these buildups as multiple, infinitesimal, repeated injuries to the blood vessel wall. Our own bodies react to these injuries, just as they would if we were bleeding from a small wound, and they respond by forming blood clots. Unfortunately, in the case of thrombotic strokes, these blood clots get caught on the plaque on the vessel walls and reduce or stop blood flow to the brain. That is when we experience a brain attack.
Two types of thrombosis can cause a stroke: large vessel thrombosis and small vessel disease. Thrombotic stroke occurs most often in the large arteries, magnifying the impact and devastation of disease. Most large vessel thrombosis is caused by a combination of long-term atherosclerosis followed by rapid blood clot formation. Many thrombotic stroke patients have coronary artery disease, and heart attacks are a frequent cause of death in patients who have suffered this type of brain attack.
The second type of thrombotic stroke is small vessel disease which occurs when blood flow is blocked to a very small arterial vessel. Little is known about the specific causes of small vessel disease, but it is often closely linked to hypertension and is an indicator of atherosclerotic disease.
In an embolic stroke, a blood clot forms somewhere in the body (usually the heart) and travels through the bloodstream to the brain. Once in the brain, the clot eventually travels to a blood vessel small enough to block its passage. The clot lodges there, blocking the blood vessel and causing a stroke.
Risk Factors
The risk factors for thrombotic stroke are the presence of hypertension, atherosclerosis, high LDL-cholesterol, excessive blood-clotting factors (such as fibrin and fibrinogen), heart valve defects, diabetes, and aging. High serum levels of homocysteine, fibrinogen, or C-reactive protein may be the strongest predictive risk factors.
A 30-year study of male twins showed that elevated blood pressure in midlife predisposed men to an increase in stroke later in life. Men with even mildly elevated blood pressure 25 years before showed smaller brain volumes and more strokes compared to their twin brothers who did not have the elevation in blood pressure (DeCarli et al. 1999). This study in the journal Stroke emphasized the importance of aggressively treating elevated blood pressure even if it is not grossly abnormal (refer to the Cardiovascular Disease protocol for information about blood pressure control therapies and diets).
Uncontrollable Risk Factors
Increasing age. The chance of having a stroke more than doubles for each decade of life after age 55. While strokes are common among the elderly, substantial numbers of people less than 65 also have strokes.
Gender. Overall, men have about a 19% greater chance of a stroke than women. Among people under age 65, the risk for men is even greater when compared to that of women.
Family history. The chance of a stroke is greater in people who have a family history of strokes.
Race. African Americans have a much higher risk of death and disability from a stroke than Caucasians, in part because African Americans have a greater incidence of high blood pressure.
Diabetes mellitus. Diabetes is an independent risk factor for stroke and is strongly correlated with high blood pressure. While diabetes is treatable, having it still increases a person's risk of a stroke. People with diabetes often also have high cholesterol and are overweight, increasing their risk even more.
Controllable Risk Factors
High blood pressure. High blood pressure is the most prominent risk factor for stroke. In fact, stroke risk varies directly with blood pressure. More widespread treatment of high blood pressure is a key reason for the decline in the death rates for strokes.
High blood levels of homocysteine, C-reactive protein, or fibrinogen. The safe ranges of these blood indicators will be described later in this protocol, along with steps that can be taken if excess levels of these stroke risk factors are detected.
Heart disease. A diseased heart increases the risk of a stroke. In fact, people with heart problems have more than twice the risk of a stroke as those with a heart that works normally. Atrial fibrillation (the rapid, uncoordinated beating of the heart's upper chambers), in particular, raises the risk for stroke. Heart attack is also the major cause of death among survivors of a stroke.
High cholesterol. High cholesterol can directly and indirectly increase stroke risk by clogging blood vessels and putting people at greater risk of coronary heart disease, another important stroke risk factor.
Sleep disordered breathing. Sleep apnea is a major cardiovascular and stroke risk factor, increasing blood pressure rates, which may cause stroke or heart attack. Studies also indicate that people with sleep apnea develop dangerously low levels of oxygen in the blood while carbon dioxide levels rise, possibly causing blood clots or even strokes to occur. Diagnosing sleep apnea early may be an important stroke prevention tool.
Prior stroke. The risk of a stroke for someone who has already had one is several times that of a person who has not.
Carotid artery disease. The carotid arteries in your neck supply blood to your brain. A carotid artery damaged by atherosclerosis (a fatty buildup of plaque in the artery wall) may become blocked by a blood clot which may result in a stroke. If you have a diseased carotid artery, your healthcare provider may hear an abnormal sound in your neck (called a bruit) when listening with a stethoscope.
Transient ischemic attacks (TIAs). TIAs are mini-strokes that produce stroke-like symptoms, but no lasting damage. They are strong predictors of a stroke. A person who has had one or more TIAs is almost 10 times more likely to have a stroke than someone of the same age and sex who has not.
TIAs are extremely important stroke warning signs. Do not ignore them!
High red blood cell count. A moderate or marked increase in red blood cell count is a risk factor for stroke. The reason is that more red blood cells thicken the blood and make clots more likely.
Lifestyle Factors
Cigarette smoking. Studies have shown cigarette smoking, including secondhand cigarette smoke, to be an important risk factor for stroke. The nicotine and carbon monoxide in cigarette smoke damage the cardiovascular system in many ways. The use of oral contraceptives combined with cigarette smoking also greatly increases stroke risk.
Excessive alcohol intake. Excessive drinking (an average of more than one drink a day for women and more than two drinks per day for men) and binge drinking can raise blood pressure; contribute to obesity, high triglycerides, cancer, and other diseases; and cause heart failure, leading to stroke.
Weight. Excess weight puts a strain on the entire circulatory system. It also makes people more likely to have other stroke risk factors such as high cholesterol, high blood pressure, and diabetes
Other potential risk factors
Geographic location. Stroke is more common in the southeastern United States than in other areas. These are the so-called stroke belt states. The age-adjusted death rates from a stroke are much higher in these states than in the rest of the country.
Season and climate. Stroke deaths occur more often during periods of extremely hot or cold temperatures.
Socioeconomic factors. There is some evidence that people of lower income and educational levels have a higher risk for stroke.
Certain kinds of drug abuse. IV drug abuse carries a high risk of stroke from cerebral embolisms. Cocaine use has been closely related to strokes, heart attacks, and a variety of other cardiovascular complications. Some of them have been fatal even in first-time cocaine users.
Recognizing stroke symptoms and realizing that the symptoms require immediate emergency treatment can save your life!
Prevention
There are conventional drugs that can be prescribed to reduce the risk of a second stroke:
- Appropriate treatment of hypertension (high blood pressure) clearly reduces the risk of stroke. Refer to the Hypertension section of the Cardiovascular Disease protocol for information about controlling blood pressure that your physician may be overlooking.
- Low-dose aspirin is considered first-line therapy for the stroke prevention in those with high risk.
- Anticoagulant drugs such as Coumadin (warfarin) interfere with the initiation of the coagulation cascade and significantly reduce the risk that a blood clot will form. Coumadin is so side-effect prone that it is reserved for extremely high-risk individuals such as those with mechanical aortic valve replacements.
- Antiplatelet drugs such as Ticlid (ticlopidine) or Trental (pentoxifylline) inhibit platelet aggregation, thereby reducing the risk of a new blood clot forming in the brain.
The use of anticoagulant drugs involves frequent blood testing and adjusting of dose because the anticoagulating response to these drugs varies between individuals. These drugs do not do anything to the clots that may already have been formed. The side effects of anticoagulant drugs mandate careful monitoring, and some people avoid these drugs because of the risk of serious side effects.
A more benign approach is to combine aspirin with nutrients like ginkgo biloba, melatonin, fish oil, garlic, and green tea extract that are relatively free of side effects. A discussion of the pros and cons of Coumadin versus aspirin therapy can be found in the Thrombosis Prevention protocol. Those at very high risk for developing a blood clot often have to take Coumadin. |