Atherosclerosis

In atherosclerosis (sometimes called hardening of the arteries), the walls of arteries thicken as well as harden.

Atherosclerosis begins when cholesterol and other fatty materials in the blood gradually accumulate in arteries and form deposits (plaques or atheromas). Over time, calcium accumulates in the plaques, making them stiff and causing them to enlarge. As the plaques enlarge, they reduce blood flow and sometimes block it.

See the figure Atherosclerosis: Blocking an Artery.

Atherosclerosis often begins during early adulthood. However, blood flow must be reduced by at least 70% before symptoms are likely to occur. Several decades usually pass before atherosclerosis progresses to this point. Thus, it is commonly thought of as an older person's disease. Atherosclerosis is very common in the United States, Canada, Australia, and most of Europe.

Atherosclerosis tends to affect arteries throughout the body. It can affect arteries that carry blood to the heart (causing coronary artery disease), brain (sometimes resulting in a stroke), or other parts of the body (causing peripheral arterial disease).

As atherosclerosis progresses, the affected arteries lose their elasticity. Then they cannot expand (dilate) normally when blood is pumped into them. Consequently, high blood pressure may develop or worsen. Blood clots (thrombi) may form on plaques. Plaques sometimes rupture, making blood clots even more likely to form. A clot can partially or completely block blood flow through the artery. Part of a plaque or a blood clot on a plaque may break off, travel through the bloodstream (becoming an embolus), and block an artery elsewhere in the body. Sometimes an artery that is partially blocked by a plaque is suddenly blocked when a blood clot lodges in it.

Causes

What triggers plaques to form is unclear. But the trigger may be damage to the lining of an artery. Such damage enables cholesterol and other fatty materials to accumulate in the artery.

Certain conditions (called risk factors) make atherosclerosis more likely to develop or worsen. Some risk factors cannot be changed. They include a family history of early atherosclerosis (having a close relative who developed the disease at a young age), older age, and male sex. Other risk factors can usually be corrected or treated. They include abnormal levels of cholesterol and other fats (lipids) in the blood, high blood pressure, diabetes, smoking and exposure to tobacco smoke, excess body weight, and physical inactivity.

Having a high level of low-density lipoprotein (LDL, the "bad" cholesterol) or a low level of high-density lipoprotein (HDL, the "good" cholesterol) increases the risk of atherosclerosis. Generally, experts recommend that the LDL cholesterol level be less than 100 mg/dL (milligrams per deciliter of blood) and that the HDL cholesterol level be more than 40 mg/dL. The total cholesterol level includes LDL and HDL cholesterol. For most people, the total cholesterol level should be less than 200 mg/dL. The risk of a heart attack more than doubles when the total cholesterol level reaches 300 mg/dL. The percentage of HDL cholesterol in relation to total cholesterol is an especially useful measure of risk. HDL cholesterol should account for at least 25% of total cholesterol. A high level of triglycerides, another fat in the blood, is also a risk factor. After a person fasts for at least 8 hours, the triglyceride level should be less than 150 mg/dL.

Cholesterol levels increase as people age. Diet and genes also affect cholesterol and triglyceride levels. For most people, a diet high in saturated fats, trans fatty acids (artificially hydrogenated fats), and simple or refined carbohydrates increases the total cholesterol level. Eating excess calories can result in a high triglyceride level, as can drinking large amounts of alcohol. However, for some people, diet has little effect. Some people can eat large amounts of saturated fat and trans fatty acids, and their total cholesterol level stays at an acceptable level. Others can follow a strict low-fat diet, and their total cholesterol level remains well above the highest acceptable level. Such differences seem to be mostly determined by genes. A person's genetic makeup influences the rate at which the body makes, uses, and eliminates fats.

Abnormal cholesterol or triglyceride levels can be due to certain disorders. They include diabetes that is poorly controlled, kidney failure, some liver disorders, and an underactive thyroid gland (hypothyroidism).

Smoking increases the risk of atherosclerosis in several ways. It decreases the HDL cholesterol level and increases the triglyceride level. Smoking also increases the level of carbon monoxide in the blood. Excess carbon monoxide may make damage to the lining of arteries more likely. Smoking causes the muscle layer of the artery's wall to contract (constrict). If an artery is already partially blocked, constriction of the artery's wall decreases the amount of blood reaching the tissues even more. Also, smoking makes blood more likely to clot. Secondhand smoke—smoke breathed in from someone else's smoking—should also be avoided.

Being overweight increases the risk of atherosclerosis. It also increases the risk of high blood pressure, diabetes, and abnormal cholesterol levels—all risk factors for atherosclerosis.

Physical inactivity appears to increase the risk of atherosclerosis and several of its risk factors: high blood pressure, abnormal cholesterol levels, and being overweight.

A high level of homocysteine (an amino acid, one of the building blocks that make up protein) in the blood can directly damage the lining of arteries. As a result, plaques are more likely to develop. A high homocysteine level may also make blood clots more likely to form. The homocysteine level increases as people age. Kidney failure, some cancers (such as breast cancer), heavy smoking, or a deficiency of certain vitamins (folic acid or vitamin B₆ or B₁₂) can cause the homocysteine level to increase.

Infection can damage the lining of arteries, making atherosclerosis more likely to develop.

Symptoms and Diagnosis

Symptoms may first occur during physical activity, when tissues need more oxygen. Pain or muscle cramping may be felt, often in the legs. These symptoms occur because the artery supplying the affected area is partially blocked and is not receiving enough blood and oxygen.

Typically, symptoms such as pain, cramping or tightness in muscles, and weakness develop gradually as a plaque slowly enlarges and reduces blood flow through an artery. However, the first symptoms sometimes occur suddenly because an artery is suddenly blocked.

Other symptoms depend on where the blockage is:

• If one or more arteries supplying the heart (coronary arteries) are partially blocked, chest pain (angina) can result. If an artery is completely blocked, a heart attack can result.
• If an artery supplying the brain (a carotid or vertebral artery) is completely blocked, a stroke can result.
• If arteries in the legs are partially blocked, leg cramps (intermittent claudication) can result.
• If arteries supplying one or both kidneys become blocked, kidney failure or dangerously high blood pressure (malignant hypertension) can result.

Often, atherosclerosis is diagnosed only after it causes symptoms or other problems. Atherosclerosis is sometimes diagnosed when arteries appear outlined or highlighted on an x-ray taken for other reasons. Arteries may appear outlined because of calcium deposits in plaques. Other tests, depending on symptoms, may be done.

Prevention and Treatment

Correcting or treating risk factors can prevent atherosclerosis from worsening and may even cause some of the plaques to shrink. The sooner risk factors are changed, the greater the potential benefit. Because abnormal cholesterol levels are an important risk factor, older people should have their cholesterol levels measured even if they do not have symptoms of atherosclerosis.

Limiting the amount of saturated fats, trans fatty acids, and simple or refined carbohydrates in the diet can help control cholesterol levels. When possible, people should substitute monounsaturated fats and omega-3 fats for saturated fats and trans fatty acids.

Eating plenty of fruits, vegetables, and whole-grain foods also helps control cholesterol levels. These foods are naturally low in fat and contain no cholesterol. Many of the same foods are also rich in soluble fiber, which helps lower cholesterol levels. Examples are oat bran, oatmeal, beans, peas, rice bran, barley, citrus fruits, strawberries, and apple pulp.

If needed, drugs can be taken to control abnormal cholesterol levels. Many types of cholesterol-lowering drugs are available. For some people, taking one cholesterol-lowering drug is effective. Other people need to take two or, rarely, three drugs. Statins, such as atorvastatin, fluvastatin, pravastatin, and simvastatin, are commonly used. Bile acid binders and fibric acid derivatives are sometimes helpful. Lowering high cholesterol levels using drugs can reduce the risk of heart attacks, strokes, and death.

People should stop smoking if they smoke. Stopping smoking reduces the risk of atherosclerosis by half. The benefits of stopping smoking begin immediately and increase with time.

People with atherosclerosis should lose weight if they are overweight. Losing weight reduces the risk of several risk factors for atherosclerosis: high blood pressure, diabetes, and abnormal cholesterol levels.

Regular physical activity reduces the risk of atherosclerosis. Exercise can help change other risk factors for atherosclerosis—by lowering blood pressure and cholesterol levels and by helping with weight loss.

Eating foods rich in folic acid and vitamin B₆ and B₁₂ may help lower homocysteine levels and thus decrease the risk of atherosclerosis. Such foods include raw leafy green vegetables, citrus fruits, mushrooms, nuts, and enriched breads, pastas, and cereals. Even with changes in diet, some older people may still have low levels of folic acid and vitamins B₆ and B₁₂. Therefore, many experts recommend taking a daily multivitamin supplement containing these vitamins.

Symptoms and other problems due to atherosclerosis are treated. Specific treatment is needed for angina, heart attacks, strokes, and peripheral arterial disease.

See the table Levels of Fats in the Blood.

See the table Fats in Food.

See the table Cholesterol-Lowering Drugs.