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Stroke due to Atherosclerosis
What is Atherosclerosis? – Symptoms of Atherosclerosis – Brain Circulation and Stroke – Atherosclerotic Stroke Prevention – Prognosis
What is Atherosclerosis?
Atherosclerosis is a metabolic disorder caused by faulty regulation of lipid turnover. Cholesterol is typically blamed as a bad guy. In reality, cholesterol is an essential constituent of the cell membrane. Without cholesterol our cells would literally fall apart because cholesterol molecules maintain the integrity of all cell membranes.
Cholesterol is mostly made by the liver and only about 20% is supplied with diet. Basically, it is simply ridiculous to eat the egg white and throw out the yolk just because it has cholesterol. Diet does affect atherosclerosis, however. What matters is the composition and the amount of fats consumed together with cholesterol. Diets containing large amounts of saturated fat promote atherosclerosis. On the other hand, balanced diets, containing reasonable amounts of all sorts of fat, help to prevent one.
Please see my Dietary Fat article for more details.
Cholesterol and Atherosclerosis
Elevated cholesterol level and especially “bad cholesterol” are statistically associated with increased chance of atherosclerosis. In each particular person, however, it is not so simple. Severe atherosclerosis in association with pretty much acceptable cholesterol levels as well as lack of clinically significant atherosclerosis in people with bad cholesterol profiles are not uncommon.
Cholesterol lowering drugs prevent atherosclerosis by much more complex mechanism than by mere lowering of cholesterol level and normalizing HDL/LDL ratio. Some drugs developed by pharmaceutical industry don’t get approved by FDA because they normalize cholesterol numbers but have no effect on atherosclerosis progression.
Atherosclerosis starts in very young age. The majority of adults have at least some degree of atherosclerotic changes in the arteries. Cholesterol gets deposited in the arterial walls, causing degenerative changes, inflammation, and thickening of the wall. Artery wall area affected by cholesterol deposits is often called an atherosclerotic plaque. Blood clots may be formed on the surface of the plaque.
Tendency to develop atherosclerosis is often genetically predetermined. Normally, the body regulates the amount of cholesterol produced depending on the dietary supply. Some people are more sensitive than others to cholesterol in the diet due to faulty regulatory mechanisms. Life style, levels of emotional stress and physical activity are some of the contributing factors. Diabetes and hypertension increase severity of atherosclerosis.
Atherosclerosis may affect any artery, causing gradual narrowing of the blood vessel. The actual symptoms of this disease depend on the organ(s) affected.
Narrowing of the renal (kidney) artery often causes hypertension long before the kidney function suffers.
Narrowing of the leg arteries may cause intermittent claudication. It is when walking a relatively short distance causes tightness, pain, and fatigue in the leg muscles. The symptoms are relieved by rest.
Coronary (heart) artery disease is an atherosclerosis of the blood vessels supplying the heart muscle. It causes multiple heart issues, such as chest pain on exertion, heart attack (a permanent injury to some portion of the heart muscle), or heart rhythm abnormalities.
Most of body organs may sustain a significant reduction of blood flow (for hours) before any permanent tissue damage would develops. Brain is the least forgiving organ. Nerve cells tolerate shortage of oxygen and nutrient supply very poorly. Atherosclerosis of the arteries supplying the brain is frequently responsible for ischemic strokes.
Brain Circulation and Stroke
Brain is supplied by two large arteries on each side. Carotid arteries are in the front of the neck; they supply approximately 2/3 of the frontal part of the brain. Vertebral arteries approach the brain from the back of the neck and supply the rest of the brain. Even though each particular artery serves its own part of the brain, there is always a significant overlap between the supply areas.
At the base of the brain, there are direct connections between all four vessels called a Circle of Willis. Only about 1/3 of people have ideally formed Circle of Willis. The rest have one or more connections missing. The purpose of this structure is self-explanatory; if one artery fails, the rest will take care of the circulation.
It is not uncommon to accidentally find one of carotid arteries completely blocked without any sign of stroke. It usually happens when the artery is narrowing gradually. Tiny connections between branches of major arteries throughout the brain widen over time and form collateral circulation. People with completely formed Circle of Willis may have no stroke even with a rapid occlusion of one of the carotid arteries. Once I saw a man with complete occlusion of both carotid arteries. His vertebral arteries were finger thick. They were doing a good job by supplying the whole brain with blood. There were no strokes on the MRI.
Atherosclerotic plaques usually form gradually over many years. It takes a long time to narrow the vessels to the point when the circulation starts to suffer. These old calcified plaques often pose little immediate danger.
The most harmful are atherosclerotic plaques that are developing fast, have ulcer on the surface, or are falling apart. These plaques have low density and are often described as soft or hypoechoic on ultrasound studies. They don’t have to be very large to cause troubles. Fragments of these unstable plaques may travel with the blood flow and plug some brain artery causing an embolic stroke.
Atherosclerotic Stroke – Racial Differences
Strokes may be caused by atherosclerosis of large neck arteries supplying the brain, or it may affect smaller branches inside the skull. The distribution of atherosclerosis strongly correlates with the race.
Whites tend to have large artery disease (Carotid and Vertebral arteries).
Asians often have atherosclerosis of the smaller intracranial (inside the skull) arteries.
Intracranial atherosclerosis is also more common in Hispanics and Blacks than in whites.
Atherosclerosis Related Stroke Prevention
Stroke prevention treatment in atherosclerosis depends on multiple factors: artery(s) affected, severity of stenosis, age, sex, history of prior strokes, additional risk factors, and coexisting medical conditions. Severe carotid artery stenosis is often treated surgically or by endovascular stenting.
Vertebral artery stenosis and smaller brain vessel disease are most commonly managed conservatively (statins and anti-platelet drugs).
There are two groups of medications used for stroke prevention in atherosclerosis: statins and anti-platelet agents. Both groups are often used concomitantly in the same patient because they have different mechanisms of action and side effect profiles.
Statins in Atherosclerosis
Statins (atorvastatin, pravastatin, simvastatin, fluvastatin, rosuvastatin) decrease concentration of LDL cholesterol, or “bad cholesterol”. Effects of statins on atherosclerosis are much more complex than lowering LDL cholesterol level. Statin decrease inflammation within the plaques and stabilize them, improve endothelial cells (inner lining of blood vessels) function, have antioxidant qualities, modulate immune system, modulate platelet function.
In the long run, statins may even shrink atherosclerotic plaques to some extent.
Anti-platelet Drugs in Atherosclerosis
Aspirin 81 mg per day is often a first choice in stroke prevention. It is inexpensive and well tolerated. Long half-life makes it easy to use because a single missed dose doesn’t affect its stroke preventive properties that much. Stroke preventive properties of aspirin are rather modest – 15% to 20% risk reduction vs. placebo. Gastrointestinal bleeding side effect is the major concern. About 25% to 30% of people are resistant to aspirin stroke preventive effect. It is not clear, if the dose increase overcomes aspirin resistance.
Clopidogrel typical dose is 75 mg per day. It is more effective than aspirin. Relative to aspirin, clopidogrel adds additional 9% stroke reduction. Clopidogrel is probably more effective in diabetes and with history of prior strokes. Gastrointestinal bleeding side effects are less common than for aspirin. The most common side effects are skin rashes and bruising.
Aggrenox (Aspirin 25 mg and extended release Dipyridamole 200 mg)
Aggrenox is superior to aspirin alone in stroke prevention. Headache and stomach upset are common and often lead to discontinuation of the drug. It has to be taken twice a day. This drug combination is also associated with higher risk of bleeding from any source.
Aspirin-Clopidogrel combination is not proven to be superior in stroke prevention than Clopidogrel alone. Besides, this combination doubles the chance of bleeding complications, compared to Clopidogrel.
Atherosclerotic Stroke Prognosis
Prognosis of stroke in atherosclerosis depends on multiple factors: extent of the disease, individual anatomical variations of circulation, age, sex, and presence of other health issues. High blood glucose level in diabetes, for example, adversely affects nerve cells survival after stroke.
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