Atherosclerosis
Atherosclerosis is a condition in which patchy deposits of fatty material (atheromas or atherosclerotic plaques) develop in the walls of medium-sized and large arteries, leading to reduced or blocked blood flow.
In the United States and most other Western countries, atherosclerosis is the leading cause of illness and death. In the United States alone, it caused almost 1 million deaths in 1996--twice as many as cancer caused and 10 times as many as accidents caused. Despite significant medical advances, heart attacks due to coronary artery disease (atherosclerosis that affects the arteries supplying blood to the heart (see Section 3, Chapter 33)) and strokes (due to atherosclerosis that affects the arteries to the brain (see Section 6, Chapter 86)) are responsible for more deaths than all other causes combined.
Atherosclerosis can affect the medium-sized and large arteries of the brain, heart, kidneys, other vital organs, and legs. It is the most important and most common type of arteriosclerosis, a general term for several diseases in which the wall of an artery becomes thicker and less elastic.
There are two main theories about why atherosclerosis develops: High levels of cholesterol in the blood injure the artery's lining, causing an inflammatory reaction and enabling cholesterol and other fatty materials to accumulate there. Or, repeated injury to the artery's wall may occur through various mechanisms involving the immune system or through direct toxicity. In both cases, there are changes that can lead to the formation of atheromas. The two theories are probably interrelated and are not mutually exclusive.
Atherosclerosis is thought to also involve inflammation, because certain white blood cells--lymphocytes, monocytes, and macrophages--are present throughout the development of atherosclerosis. These cells usually gather only when inflammation develops. Atherosclerosis begins when monocytes are activated and move out of the bloodstream into the wall of an artery. There, they are transformed into foam cells, which collect cholesterol and other fatty materials. In time, these fat-laden foam cells accumulate. They form patchy deposits (atheromas) in the lining of the artery's wall, causing a thickening there.
Infection may have a role in the development of atherosclerosis. The infection may be due to bacteria (Chlamydia pneumoniae, which can cause pneumonia, or Helicobacter pylori, which can contribute to stomach ulcers) or to a virus (as yet unidentified). Infection may damage the lining of the artery's wall, enabling atherosclerosis to begin.
Atheromas may be scattered throughout medium-sized and large arteries, but they usually form where the arteries branch--presumably because the constant turbulent blood flow at these areas injures the artery's wall, making these areas more susceptible to atheroma formation.
 See the figure How Atherosclerosis Develops.
Arteries affected by atherosclerosis also lose their elasticity, possibly contributing to high blood pressure. As the atheromas grow, the interior (lumen) of the arteries narrows. With time, calcium accumulates in the atheromas, which may become brittle and rupture. Blood may enter a ruptured atheroma, making it larger, so that it narrows the artery even more. A ruptured atheroma also may spill its fatty contents into the bloodstream. This fatty mass (fat embolus) may travel through the bloodstream and block an artery elsewhere in the body. More often, the rupture of an atheroma triggers the formation of a blood clot (thrombus), which is the main cause of a heart attack or stroke. The clot may further narrow or even block the artery, or the clot may detach (becoming an embolus), travel through the bloodstream, and block another artery downstream.
 See the sidebar What Is Arteriosclerosis?
 See the animation Fatty Deposits in a Coronary Artery.
Risk Factors
Risk factors for atherosclerosis include smoking, high levels of cholesterol in the blood, high blood pressure, diabetes, obesity, physical inactivity, and high blood levels of homocysteine (an amino acid). These risk factors can usually be modified (see Section 3, Chapter 33). Risk factors that cannot be modified include having a family history of early atherosclerosis (that is, having a close relative who developed the disease at a young age), advancing age, and male sex. Men have a higher risk than women, although women who have coronary artery disease are more likely to die than men who have the disease.
Smoking: One of the most important modifiable risk factors is smoking. A smoker's risk of developing coronary artery disease is directly related to the number of cigarettes smoked daily. In people who already have a high risk of heart disease, smoking is particularly dangerous.
Smoking decreases the level of high-density lipoprotein (HDL) cholesterol--the "good" cholesterol--and increases the level of low-density lipoprotein (LDL) cholesterol--the "bad" cholesterol. Smoking increases the level of carbon monoxide in the blood, which may increase the risk of injury to the lining of the artery's wall. Smoking causes arteries already narrowed by atherosclerosis to constrict, further decreasing the amount of blood reaching the tissues. In addition, smoking increases the blood's tendency to clot (by making platelets stickier), so that it increases the risk of peripheral arterial disease (atherosclerosis affecting arteries other than those that supply the heart and brain) (see Section 3, Chapter 34), coronary artery disease (see Section 3, Chapter 33), stroke (see Section 6, Chapter 86), and blockage of an arterial graft placed during bypass surgery (see Section 3, Chapter 33 and Section 3, Chapter 34).
People who quit smoking have only half the risk of those who continue to smoke--regardless of how long they smoked before quitting. Quitting also decreases the risk of death after coronary artery bypass surgery or a heart attack and the risk of illness and death in people who have peripheral arterial disease. The benefits of quitting smoking begin immediately and increase with time.
Secondhand smoke (smoke breathed in from someone else's smoking) appears to increase risk also. It should be avoided.
High Cholesterol Levels: A high cholesterol level is another important modifiable risk factor. Lowering high cholesterol levels through the use of statins (see Section 12, Chapter 157) can significantly reduce the risk of heart attacks, strokes, and death. Many of the risk factors for high cholesterol levels are also risk factors for atherosclerosis. They include smoking, diabetes, obesity, and physical inactivity. A high-fat diet causes cholesterol levels to increase in susceptible people. Cholesterol levels increase as people age and are normally higher in men than in women, although levels increase in women after menopause.
However, not all types of cholesterol increase the risk of atherosclerosis. A high level of LDL (bad) cholesterol increases the risk. A high level of HDL (good) cholesterol decreases the risk, and a low level increases the risk. Ideally, the level of total cholesterol, which includes LDL and HDL cholesterol and triglycerides, is 140 to 200 mg/dL. Risk of a heart attack more than doubles when the total cholesterol level approaches 300 mg/dL. The risk is decreased when the LDL cholesterol level is below 130 mg/dL, and the HDL cholesterol level is above 40 mg/dL (see Section 12, Chapter 157). However, the percentage of HDL cholesterol in relation to total cholesterol is a more reliable measure of risk than is the total or LDL cholesterol level. HDL cholesterol should account for more than 25% of total cholesterol. High triglyceride levels are often associated with low HDL cholesterol levels. However, evidence suggests that high triglyceride levels alone may also increase the risk of atherosclerosis.
Several hereditary disorders that result in high levels of cholesterol or other fats also increase the risk of atherosclerosis. For example, familial hypercholesterolemia, which can result in extremely high levels of cholesterol, causes atheromas to form, primarily in the coronary arteries. People who have this disease and are untreated die of coronary artery disease at an early age.
High Blood Pressure: Uncontrolled high diastolic or systolic blood pressure is a risk factor for heart attack and stroke, which are caused by atherosclerosis.
Diabetes Mellitus: People who have type I diabetes (see Section 13, Chapter 165) tend to develop atherosclerosis that affects small arteries, such as those in the eyes and kidneys. Some people with type I diabetes and most people with type II diabetes tend to develop atherosclerosis in large arteries. These people also tend to develop atherosclerosis at an earlier age and more extensively than do people who do not have diabetes. The risk of developing atherosclerosis is 2 to 6 times higher for people with diabetes, particularly women. Women who have diabetes, unlike those who do not, are not protected from atherosclerosis before menopause.
Obesity: Obesity, particularly abdominal (truncal) obesity, increases the risk of coronary artery disease (atherosclerosis of the arteries that supply blood to the heart). Abdominal obesity increases the risk of other risk factors for atherosclerosis: high blood pressure, type 2 diabetes, and high cholesterol levels. Losing weight reduces the risk of all these disorders.
Physical Inactivity: Physical inactivity appears to increase the risk of developing coronary artery disease, and much evidence suggests that regular exercise reduces this risk. Exercise can also help modify other risk factors for atherosclerosis--by lowering blood pressure and cholesterol levels and by helping with weight loss.
High Blood Levels of Homocysteine (Hyperhomocysteinemia): High levels of homocysteine (an amino acid) in the blood may directly injure the lining of arteries, making the formation of atheromas more likely. High homocysteine levels may also promote the formation of blood clots. Homocysteine levels increase with age, particularly after menopause. High homocysteine levels in the blood may be caused by homocystinuria (a hereditary disorder that causes excessive excretion of homocysteine in the urine). People who have this disorder develop extensive atherosclerosis, often at a young age. Atheromas form in many arteries, but not primarily in the coronary arteries, which supply the heart.
If hyperhomocysteinemia is due to a condition other than hereditary homocystinuria, the risk of atherosclerosis affecting the coronary arteries (as well as the arteries to the brain and the peripheral arteries) is increased. Conditions that may increase homocysteine levels in the blood include a deficiency of folic acid or of vitamin B6 or B12, kidney failure, some cancers (such as breast cancer), psoriasis, heavy smoking, and use of certain drugs. These drugs include those that interact with folic acid or vitamin B6 or B12, such as methotrexate (used to treat cancer) and the anticonvulsants phenytoin and carbamazepine; drugs that interfere with the absorption of homocysteine, such as the cholesterol-lowering drugs colestipol, cholestyramine, and niacin; and drugs that interfere with the metabolism of homocysteine, such as the antibiotic isoniazid.
Symptoms
Usually, atherosclerosis does not produce symptoms until it narrows the interior of an artery by more than 70%. Symptoms depend on where the narrowing or blockage, which can occur almost anywhere in the body, is. If the arteries supplying the heart (coronary arteries) are narrowed, chest pain (angina) can result; if they are blocked, a heart attack can result. Abnormal heart rhythms and heart failure may also develop. Blockage in the arteries supplying the brain (carotid arteries) can cause a stroke. Narrowing of the arteries in the legs can cause leg cramps (intermittent claudication (see Section 3, Chapter 34)). In people older than 55, the arteries supplying one or both kidneys may become narrowed or blocked, sometimes causing kidney failure or dangerously high blood pressure (malignant hypertension (see Section 3, Chapter 22)).
Symptoms occur because as atherosclerosis narrows an artery more and more, tissues supplied by the artery may not receive enough blood and oxygen. The first symptom of a narrowing artery may be pain or cramps at times when blood flow cannot keep up with the tissues' need for oxygen. For instance, during exercise, a person may feel chest pain because the oxygen supply to the heart is inadequate; while walking, a person may feel leg cramps because the oxygen supply to the legs is inadequate.
Typically, symptoms develop gradually as the atheroma slowly narrows an artery. However, sometimes the first symptoms occur suddenly because the blockage occurs suddenly--for example, when a blood clot lodges in an artery narrowed by an atheroma, causing a heart attack or stroke.
Prevention and Treatment
To help prevent atherosclerosis, a person needs to be aware of the risk factors that can be modified--for example, smoking, high blood cholesterol levels, high blood pressure, obesity, and physical inactivity. So depending on a person's risk factors, prevention may consist of quitting smoking (see Section 3, Chapter 33), lowering cholesterol levels (see Section 12, Chapter 157), lowering blood pressure (see Section 3, Chapter 22), losing weight (see Section 12, Chapter 156), and beginning an exercise program (see Section 1, Chapter 6).
When atherosclerosis becomes severe enough to cause complications, the complications themselves must be treated. Complications include angina, heart attack, abnormal heart rhythms, heart failure, kidney failure, stroke, and leg cramps (intermittent claudication).
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