Atherosclerosis

Definition

Atherosclerosis is the build up of a waxy plaque on the inside of blood vessels. In Greek, athere means gruel, and skleros means hard. Atherosclerosis is often called arteriosclerosis. Arteriosclerosis (from the Greek arteria, meaning artery ) is a general term for hardening of the arteries. Arteriosclerosis can occur in several forms, including atherosclerosis.

Description

Atherosclerosis, a progressive process responsible for most heart disease, is a type of arteriosclerosis or hardening of the arteries. An artery is made up of several layers: an inner lining called the endothelium, an elastic membrane that allows the artery to expand and contract, a layer of smooth muscle, and a layer of connective tissue. Arteriosclerosis is a broad term that includes a hardening of the inner and middle layers of the artery. It can be caused by normal aging, by high blood pressure, and by diseases such as diabetes. Atherosclerosis is a type of arteriosclerosis that affects only the inner lining of an artery. It is characterized by plaque deposits that block the flow of blood.

Plaque is made of fatty substances, cholesterol, waste products from the cells, calcium, and fibrin, a stringy material that helps clot blood. The plaque formation process stimulates the cells of the artery wall to produce substances that accumulate in the inner layer. Fat builds up within these cells and around them, and they form connective tissue and calcium. The inner layer of the artery wall thickens, the artery's diameter is reduced, and blood flow and oxygen delivery are decreased. Plaques can rupture or crack open, causing the sudden formation of a blood clot (thrombosis). Atherosclerosis can cause a heart attack if it completely blocks the blood flow in the heart (coronary) arteries. It can cause a stroke if it completely blocks the brain (carotid) arteries. Atherosclerosis can also occur in the arteries of the neck, kidneys, thighs, and arms, causing kidney failure or gangrene and amputation.

Causes and symptoms

Atherosclerosis can begin in the late teens, but it usually takes decades to cause symptoms. Some people experience rapidly progressing atherosclerosis during their thirties, others during their fifties or sixties. Atherosclerosis is complex. Its exact cause is still unknown. It is thought that atherosclerosis is caused by a response to damage to the endothelium from high cholesterol, high blood pressure, and cigarette smoking. A person who has all three of these risk factors is eight times more likely to develop atherosclerosis than is a person who has none. Physical inactivity, diabetes, and obesity are also risk factors for atherosclerosis. High levels of the amino acid homocysteine and abnormal levels of protein-coated fats called lipoproteins also raise the risk of coronary artery disease. These substances are the targets of much current research. The role of triglycerides, another fat that circulates in the blood, in forming atherosclerotic plaques is unclear. High levels of triglycerides are often associated with diabetes, obesity, and low levels of high-density lipoproteins (HDL cholesterol). The more HDL ("good") cholesterol, in the blood, the less likely is coronary artery disease. These risk factors are all modifiable. Non-modifiable risk factors are heredity, sex, and age.

Risk factors that can be changed:

• Cigarette/tobacco smoke-Smoking increases both the chance of developing atherosclerosis and the chance of dying from coronary heart disease. Second hand smoke may also increase risk.
• High blood cholesterol-Cholesterol, a soft, waxy substance, comes from foods such as meat, eggs, and other animal products and is produced in the liver. Age, sex, heredity, and diet affect cholesterol. Total blood cholesterol is considered high at levels above 240 mg/dL and borderline at 200-239 mg/dL. High-risk levels of low-density lipoprotein (LDL cholesterol) begin at 130-159 mg/dL.
• High triglycerides-Most fat in food and in the body takes the form of triglycerides. Blood triglyceride levels above 400 mg/dL have been linked to coronary artery disease in some people. Triglycerides, however, are not nearly as harmful as LDL cholesterol.
• High blood pressure-Blood pressure of 140 over 90 or higher makes the heart work harder, and over time, both weakens the heart and harms the arteries.
• Physical inactivity-Lack of exercise increases the risk of atherosclerosis.
• Diabetes mellitus-The risk of developing atherosclerosis is seriously increased for diabetics and can be lowered by keeping diabetes under control. Most diabetics die from heart attacks caused by atherosclerosis.
• Obesity-Excess weight increases the strain on the heart and increases the risk of developing atherosclerosis even if no other risk factors are present.

Risk factors that cannot be changed:

• Heredity-People whose parents have coronary artery disease, atherosclerosis, or stroke at an early age are at increased risk. The high rate of severe hypertension among African-Americans puts them at increased risk.
• Sex-Before age 60, men are more likely to have heart attacks than women are. After age 60, the risk is equal among men and women.
• Age-Risk is higher in men who are 45 years of age and older and women who are 55 years of age and older.

Symptoms differ depending upon the location of the atherosclerosis.

• In the coronary (heart) arteries: Chest pain, heart attack, or sudden death.
• In the carotid (brain) arteries: Sudden dizziness, weakness, loss of speech, or blindness.
• In the femoral (leg) arteries: Disease of the blood vessels in the outer parts of the body (peripheral vascular disease) causes cramping and fatigue in the calves when walking.
• In the renal (kidney) arteries: High blood pressure that is difficult to treat.

Diagnosis

Physicians may be able to make a diagnosis of atherosclerosis during a physical exam by means of a stethoscope and gentle probing of the arteries with the hand (palpation). More definite tests are electrocardiography, echocardiography or ultrasonography of the arteries (for example, the carotids), radionuclide scans, and angiography.

An electrocardiogram shows the heart's activity. Electrodes covered with conducting jelly are placed on the patient's body. They send impulses of the heart to a recorder. The test takes about 10 minutes and is performed in a physician's office. Exercise electrocardiography (stress test ) is conducted while the patient exercises on a treadmill or a stationary bike. It is performed in a physician's office or an exercise laboratory and takes 15-30 minutes.

Echocardiography, cardiac ultrasound, uses sound waves to create an image of the heart's chambers and valves. A technician applies gel to a hand-held transducer, presses it against the patient's chest, and images are displayed on a monitor. This technique cannot evaluate the coronary arteries directly. They are too small and are in motion with the heart. Severe coronary artery disease, however, may cause abnormal heart motion that is detected by echocardiography. Performed in a cardiology outpatient diagnostic laboratory, the test takes 30-60 minutes. Ultrasonography is also used to assess arteries of the neck and thighs.

Radionuclide angiography and thallium (or sestamibi) scanning enable physicians to see the blood flow through the coronary arteries and the heart chambers. Radioactive material is injected into the bloodstream. A device that uses gamma rays to produce an image of the radioactive material (gamma camera) records pictures of the heart. Radionuclide angiography is usually performed in a hospital's nuclear medicine department and takes 30-60 minutes. Thallium scanning is usually done after an exercise stress test or after injection of a vasodilator, a drug to enlarge the blood vessels, like dipyridamole (Persantine). Thallium is injected, and the scan is done then and again four hours (and possibly 24 hours) later. Thallium scanning is usually performed in a hospital's nuclear medicine department. Each scan takes 30-60 minutes.

Coronary angiography is the most accurate diagnostic method and the only one that requires entering the body (invasive procedure). A cardiologist inserts a catheter equipped with a viewing device into a blood vessel in the leg or arm and guides it into the heart. The patient has been given a contrast dye that makes the heart visible to x rays. Motion pictures are taken of the contrast dye flowing though the arteries. Plaques and blockages, if present, are well defined. The patient is awake but has been given a sedative. Coronary angiography is performed in a cardiac catheterization laboratory and takes from 30 minutes to two hours.

Treatment

Treatment includes lifestyle changes, lipid-lowering drugs, percutaneous transluminal coronary angioplasty, and coronary artery bypass surgery. Atherosclerosis requires lifelong care.

Patients who have less severe atherosclerosis may achieve adequate control through lifestyle changes and drug therapy. Many of the lifestyle changes that prevent disease progression-a low-fat, low-cholesterol diet, losing weight (if necessary), exercise, controlling blood pressure, and not smoking-also help prevent the disease.

KEY TERMS

Arteriosclerosis— Hardening of the arteries. It includes atherosclerosis, but the two terms are often used synonymously.

Cholesterol— A fat-like substance that is made by the human body and eaten in animal products. Cholesterol is used to form cell membranes and process hormones and vitamin D. High cholesterol levels contribute to the development of atherosclerosis.

HDL Cholesterol— About one-third or one-fourth of all cholesterol is high-density lipoprotein cholesterol. High levels of HDL, nicknamed "good" cholesterol, decrease the risk of atherosclerosis.

LDL Cholesterol— Low-density lipoprotein cholesterol is the primary cholesterol molecule. High levels of LDL, nicknamed "bad" cholesterol, increase the risk of atherosclerosis

Plaque— A deposit of fatty and other substances that accumulates in the lining of the artery wall.

Triglyceride— A fat that comes from food or is made from other energy sources in the body. Elevated triglyceride levels contribute to the development of atherosclerosis.

Most of the drugs prescribed for atherosclerosis seek to lower cholesterol. Many popular lipid-lowering drugs can reduce LDL-cholesterol by an average of 25-30% when combined with a low-fat, low-cholesterol diet. Lipid-lowering drugs include bile acid resins, "statins" (drugs that effect HMG-CoA reductase, an enzyme that controls the processing of cholesterol), niacin, and fibric acid derivatives such as gemfibrozil (Lobid). Aspirin helps prevent thrombosis and a variety of other medications can be used to treat the effects of atherosclerosis.

Percutaneous transluminal coronary angioplasty and bypass surgery are invasive procedures that improve blood flow in the coronary arteries. Percutaneous transluminal coronary angioplasty (coronary angioplasty) is a non-surgical procedure in which a catheter tipped with a balloon is threaded from a blood vessel in the thigh into the blocked artery. The balloon is inflated, compresses the plaque to enlarge the blood vessel, and opens the blocked artery. Coronary angioplasty is performed by a cardiologist in a hospital and generally requires a hospital stay of one or two days. It is successful about 90% of the time, but for one-third of patients the artery narrows again within six months. It can be repeated and a "stent" may be placed in the artery to help keep it open (see below).

In coronary artery bypass surgery (bypass surgery), a detour is built around the blockage with a healthy vein or artery, which then supplies oxygen-rich blood to the heart. It is major surgery appropriate for patients with blockages in two or three major coronary arteries or severely narrowed left main coronary arteries, and for those who have not responded to other treatments. It is performed in a hospital under general anesthesia and uses a heart-lung machine. About 70% of patients experience full relief; about 20% partial relief.

Three other semi-experimental surgical procedures may be used to treat atherosclerosis. In atherectomy, a cardiologist shaves off and removes strips of plaque from the blocked artery. In laser angioplasty, a catheter with a laser tip is inserted to burn or break down the plaque. A metal coil called a stent may be permanently implanted to keep a blocked artery open.

Alternative treatment

Alternative therapies that focus on diet and lifestyle can help prevent, retard, or reverse atherosclerosis. Herbal therapies that may be helpful include: hawthorn (Crataegus laevigata ), notoginseng root (Panax notoginseng ), garlic (Allium sativum ), ginger (Zingiber officinale ), hot red or chili peppers, yarrow (Achillea millefolium ), and alfalfa (Medicago sativum ). Relaxation techniques including yoga, meditation, guided imagery, biofeedback, and counseling and other "talking" therapies may also be useful to prevent or slow the progress of the disease. Dietary modifications focus on eating foods that are low in fats (especially saturated fats), cholesterol, sugar, and animal proteins and high in fiber and antioxidants (found in fresh fruits and vegetables). Liberal use of onions and garlic is recommended, as is eating raw and cooked fish, especially cold-water fish like salmon. Smoking, alcohol, and stimulants like coffee should be avoided. Chelation therapy, which uses anticoagulant drugs and nutrients to dissolve plaque and flush it through the kidneys, is controversial. Long-term remedies can be prescribed by specialists in ayurvedic medicine, which combines diet, herbal remedies, relaxation and exercise, and homeopathy, which treats a disease with small doses of a drug that causes the symptoms of the disease.

Prognosis

Atherosclerosis can be successfully treated but not cured. Recent clinical studies have shown that atherosclerosis can be delayed, stopped, and even reversed by aggressively lowering LDL cholesterol. New diagnostic techniques enable physicians to identify and treat atherosclerosis in its earliest stages. New technologies and surgical procedures have extended the lives of many patients who would otherwise have died. Research continues.

Prevention

A healthy lifestyle-eating right, regular exercise, maintaining a healthy weight, not smoking, and controlling hypertension-can reduce the risk of developing atherosclerosis, help keep the disease from progressing, and sometimes cause it to regress.

• Eat right-A healthy diet reduces excess levels of LDL cholesterol and triglycerides. It includes a variety of foods that are low in fat and cholesterol and high in fiber; plenty of fruits and vegetables; and limited sodium. Fat should comprise no more than 30%, and saturated fat no more than 8-10%, of total daily calories according to the American Heart Association. Cholesterol should be limited to about 300 milligrams per day and sodium to about 2,400 milligrams. The "Food Guide" Pyramid developed by the U.S. Departments of Agriculture and Health and Human Services provides daily guidelines: 6-11 servings of bread, cereal, rice, and pasta; 3-5 servings of vegetables; 2-4 servings of fruit; 2-3 servings of milk, yogurt, and cheese; and 2-3 servings of meat, poultry, fish, dry beans, eggs, and nuts. Fats, oils, and sweets should be used sparingly. Mono-unsaturated oils, like olive and rapeseed (Canola) are good alternatives to use for cooking.
• Exercise regularly-Aerobic exercise can lower blood pressure, help control weight, and increase HDL ("good") cholesterol. It may keep the blood vessels more flexible. Moderate to intense aerobic exercise lasting about 30 minutes (or three 10-minute exercise periods) four or more times per week is recommended, according to the Centers for Disease Control and Prevention and the American College of Sports Medicine. Aerobic exercise includes walking, jogging, and cycling, active gardening, climbing stairs, or brisk housework. A physician should be consulted before exercise if a person has atherosclerosis or is at increased risk for it.
• Maintain a desirable body weight-Losing weight can help reduce total and LDL cholesterol, reduce triglycerides, and boost HDL cholesterol. It may also reduce blood pressure. Eating right and exercising are two key components in maintaining a desirable body weight.
• Do not smoke or use tobacco-Smoking has many adverse effects on the heart but quitting can repair damage. Ex-smokers face the same risk of heart disease as non-smokers within five to 10 years of quitting. Smoking is the worst thing a person can do to their heart and lungs.
• Seek treatment for hypertension-High blood pressure can be controlled through lifestyle changesreducing sodium and fat, exercising, managing stress, quitting smoking, and drinking alcohol in moderation-and medication. Drugs that provide effective treatment are: diuretics, beta-blockers, sympathetic nerve inhibitors, vasodilators, angiotensin converting enzyme inhibitors, and calcium antagonists. Hypertension usually has no symptoms so it must be checked to be known. Like cholesterol, hypertension is called a "silent killer."

Resources

PERIODICALS

Morgan, Peggy. "What Your Heart Wishes You Knew About Cholesterol." Prevention (September 1997): 96.

ORGANIZATIONS

American Heart Association. 7320 Greenville Ave. Dallas, TX 75231. (214) 373-6300. 〈http://www.americanheart.org〉.

National Heart, Lung and Blood Institute. PO Box 30105, Bethesda, MD 20824-0105. (301) 251-1222. 〈http://www.nhlbi.nih.gov〉.

Texas Heart Institute. Heart Information Service. PO Box 20345, Houston, TX 77225-0345. 〈http://www.tmc.edu/thi〉.

Atherosclerosis

Definition

Atherosclerosis is the build up of plaque on the inside of blood vessels. Atherosclerosis is often called arteriosclerosis, which is a general term for hardening of the arteries.

Description

Atherosclerosis, a progressive condition responsible for most heart disease , is a type of hardening of the arteries. It can be caused by normal aging processes, by high blood pressure, and by some diseases, such as diabetes. Atherosclerosis can begin in the late teens, but it usually takes decades for the signs and symptoms of the disease to be apparent. Some people experience rapidly progressing atherosclerosis in their 30s or later.

An artery is made up of several layers: an inner lining called the endothelium, an elastic membrane that allows the artery to expand and contract, a layer of smooth muscle, and a layer of connective tissue. Atherosclerosis affects the inner lining of an artery. It is characterized by plaque deposits that block the flow of blood. Plaque is made of fatty substances, cholesterol , waste products from the cells, calcium, iron , and fibrin, a material that helps clot blood.

As plaque builds up in and around the cells of the artery walls, they accumulate calcium. The innermost layer thickens, the artery's diameter is reduced, and blood flow and oxygen delivery are decreased. Plaque can rupture or crack open, causing the sudden formation of a blood clot, called a thrombosis. As a result of thrombosis and/or the buildup of plaque, atherosclerosis can cause a heart attack if it completely blocks the blood flow in the coronary arteries. It can cause a stroke if it completely blocks the carotid arteries of the brain. Atherosclerosis can also occur in the arteries of the neck, kidneys, thighs, and arms, and may lead to kidney failure, gangrene , and even death.

Causes & symptoms

It is thought that atherosclerosis is caused by the body's response to damage to the artery wall from cholesterol, high blood pressure, and cigarette smoking . A person who has all three of these risk factors is eight times more likely to develop atherosclerosis than is a person who has none. Physical inactivity, damage by oxidants, diabetes, and obesity are also risk factors for atherosclerosis. High levels of the amino acid homocysteine and abnormal levels of fats called lipoproteins also raise the risk. Other risk factors include:

• High triglycerides. Most fat in food and in the body takes the form of triglycerides. Blood triglyceride levels above 400 mg/dL have been linked to atherosclerosis.
• Physical inactivity. Lack of exercise increases the risk of atherosclerosis.
• Diabetes mellitus. The risk of developing atherosclerosis is seriously increased for diabetics and can be lowered by keeping diabetes under control. Many diabetics die from heart attacks caused by atherosclerosis.
• Obesity. Excess weight increases the strain on the heart and increases the risk of developing atherosclerosis, even if no other risk factors are present.
• Heredity. People whose parents have coronary artery disease, atherosclerosis, or stroke at an early age are at increased risk.
• Sex. Before age 60, men are more likely to have heart attacks than women.
• Age. Risk is higher in men who are 45 years of age and older and women who are 55 years of age and older.

The symptoms of atherosclerosis differ depending upon the location. They may involve:

• In the coronary (heart) arteries: chest pain , heart attack, and sudden death.
• In the carotid arteries of the brain: sudden dizziness , weakness, loss of speech, and blindness.
• In the femoral arteries of the legs: cramping and fatigue in the calves of the legs when walking.
• In the renal arteries of the kidneys: high blood pressure resistant to treatment.

Diagnosis

Physicians may be able to make a diagnosis of atherosclerosis during a physical exam by means of a listening to the activity of the arteries and the heart with a stethoscope and probing them with the hands. More definitive tests are usually called for, however. These include an electrocardiogram, which shows the heart's activity; exercise electrocardiography, more familiarly known as a stress test, conducted while the patient exercises on a treadmill or a stationary bike; echocardiography, a type of ultrasound using sound waves to create an image of the heart's chambers and valves; and ultra-sonography to assess arteries of the neck and thighs.

Radionuclide angiography and thallium scanning use radioactive material injected into the bloodstream. These tests enable physicians to see the blood flow through the coronary arteries and the heart chambers and to record pictures of the heart. Coronary angiography is the most accurate diagnostic method for artheroscerosis, and it is also the only invasive procedure. A cardiologist inserts a catheter equipped with a viewing device into a blood vessel in the leg or arm and guides it into the heart. A contrast dye makes the heart visible to x rays. Motion pictures are taken of the dye flowing though the arteries, and plaques and blockages are well defined.

Treatment

The most common treatments focus on dietary and lifestyle changes to reduce cholesterol and other problems that contribute to atherosclerosis. Dietary modifications usually incorporate eating foods that are low in saturated fats, cholesterol, sugar, and animal proteins. Foods high in fiber, such as fresh fruits and vegetables, and whole grains, are encouraged. By consuming fruits and vegetables, the person also consumes helpful dietary antioxidants , such as carotenoids found in vegetable pigments, and bioflavenoids in fruit pigments. Liberal use of onions and garlic is recommended, as well as eating fish, especially cold-water fish, such as salmon. Smoking, alcohol, and coffee are to be avoided; and exercise is strongly recommended. There are several well-known programs, such as those created by Nathan and Robert Pritikin and Dean Ornish , which are very helpful in setting up and maintaining dietary and lifestyle programs.

Herbal remedies for atherosclerosis include garlic (Allium sativum ), ginger (Zingiber officinale ), hawthorn (Crataegus oxycantha ), (Ginkgo biloba ), and Siberian ginseng root (Eleutherococcus senticosus ). Gugulipids, or myrrh (Commiphora molmol ) is highly regarded for its ability to lower cholesterol and triglyceride levels. Other herbs with this ability include alfalfa (Medicago sativum ), turmeric (Curcuma longa ), (Panax ginseng ), and fenugreek (Trigonella foenum-graecum ). Atherosclerosis is a complex condition. Therefore, a knowledgeable practitioner of herbal healing should be consulted for recommendations on the right combination of herbs and dosages.

Chelation therapy involves injecting a drug called EDTA and drug taken orally called DMSA, together with nutrients into the bloodstream. It is thought to work by either binding to the calcium in plaque and transporting it for excretion, or by acting as an antioxidant, or by both methods. It has shown some success, but it remains a controversial method.

Several disciplines can offer helpful long-term treatment strategies for those with atherosclerosis. A knowledgeable practitioner should be consulted. Ayurvedic medicine practitioners combine diet, herbal remedies, relaxation , and exercises. A homeopath will prescribe a treatment regimen based on a complete assessment. A traditional Chinese medicine practitioner may prescribe a combination of herbs such as siler (Ledebouriellla divaricata ), Platycodon grandiflorum, Polygonum multiflorum, and Bupleurum chinense. Acupuncture and massage may be recommended, particularly for the accompanying circulatory problems. A homeopath will prescribe remedies based on an in-depth interview and evaluation.

Stress is known to worsen blood pressure and atherosclerosis, and hasten the progression of the disease. Therapeutic relaxation techniques are, therefore, helpful adjuncts to treatment. Recommended approaches include yoga, meditation, guided imagery, biofeedback , and counseling. In fact, a 2002 study showed that transcendental meditation, when combined with diet, exercise and antioxidant food supplements, contributed to nearly a 33% reduced long-term risk for heart attack and stroke in some patients.

Allopathic treatment

Allopathic treatment includes medications, balloon angioplasty, and coronary artery bypass surgery. Most of the drugs prescribed for atherosclerosis seek to improve conditions that contribute to the disease, such as high cholesterol, blood clots , or high blood pressure.

Angioplasty and bypass surgery are invasive procedures that improve blood flow in the coronary arteries. Coronary angioplasty is performed by a cardiologist. It is a nonsurgical procedure in which a catheter tipped with a balloon is threaded from a blood vessel in the thigh into the blocked artery. When the balloon is inflated, it compresses the plaque and enlarges the blood vessel to open the blocked artery. In one–third of patients, the artery narrows again within six months. The procedure may have to be repeated and a wire mesh stent may be placed in the artery to help keep it open. In bypass surgery, a detour is created with grafted or synthetic blood vessels. The blood can then go around the blockage. Other procedures may be used, including catheterization and laser treatments.

Expected results

Atherosclerosis can be successfully treated, but not cured. Studies have shown that atherosclerosis can be delayed, stopped, and even reversed by aggressively lowering cholesterol and changing the diet.

Prevention

A healthy lifestyle—eating right, regular exercise, maintaining a healthy weight, not smoking, and controlling hypertension—can reduce the risk of developing atherosclerosis, help keep the disease from progressing, and sometimes cause it to regress. A 2002 study presented promising news about the impact of simple exercise on modifying the elasticity of one's arteries. A small group of healthy but sedentary postmenopausal women began walking at a moderate pace for 40 to 45 minutes a day five times a week. By the end of 12 weeks, 48% of the women had restored elasticity to their carotid arteries.

Resources

BOOKS

American Heart Association and American Cancer Society, ed. Living Well, Staying Well. New York and Toronto: American Heart Association and American Cancer Society, 1996.

The Editors of Time–Life Books. The Medical Advisor: The Complete Guide to Alternative & Conventional Treatments. Virginia: Time–Life Books, 1997.

Shealy, C. Norman. The Complete Family Guide to Alternative Medicine. New York: Barnes & Noble Books, 1996.

PERIODICALS

"Research Briefs: Meditation Reduces Atherosclerosis." GP (May 13, 2002): 4.

"Walking Aids Older Women's Arterial Elasticity, Helping Heart." Women's Health Weekly (May 23, 2002): 3.

ORGANIZATIONS

American Heart Association, National Center. 7272 Greenville Avenue, Dallas, TX 75231–4596, <http://www.amhrt.org.>

National Heart, Lung, and Blood Institute. P.O. Box 30105, Bethesda, MD 20824–0105. <http://www.nhlbi.nih.gov/nhlbi/nhlbi.htm.>

Patience Paradox

Teresa G. Odle

Atherosclerosis

Definition

Atherosclerosis is a disease in which fatty materials build up and harden in the walls of the arteries and obstruct blood flow. Atherosclerosis is a specific kind of arteriosclerosis, although these two terms are often used interchangeably. In common terms, atherosclerosis is called hardening of the arteries.

Description

Healthy arteries are strong, elastic blood vessels that carry oxygen-rich blood to all parts of the body. As a person ages, fatty material develops in the walls of the arteries. As more and more of this material, called plaque, is produced and hardens, it blocks blood flow through the artery. Many people also develop hypertension (high blood pressure ). Over a long period, high blood pressure puts extra strain on the arteries causing them to lose some of their elasticity. This combination of loss of elasticity and blocked blood flow results in the condition called atherosclerosis or hardening of the arteries. The functional effect of atherosclerosis is that when the artery is 50–70% obstructed an insufficient amount of blood reaches vital organs in the body and permanent damage occurs.

Atherosclerosis can develop in any artery. Special names are given to some of the more common conditions caused by atherosclerosis.

• coronary artery disease: atherosclerosis of the coronary arteries. The coronary arteries are the first arteries to branch off the aorta (the large artery leaving the heart). They supply the heart with oxygen-rich blood. Blockage of these arteries can cause chest pain (angina), weakness in the heart muscle, and heart attack (myocardial infarction).
• peripheral vascular disease: atherosclerosis of arteries outside the head and trunk, usually in the arms and legs. Peripheral artery disease results in poor circulation to these areas. Symptoms include the hands and feet always feeling cold, poor wound healing, intermittent pain while walking (claudication), and male impotence.
• aneurysm: a weak spot where the artery wall bulges. The artery may rupture at the weak spot and cause death. The most common sites for aneurysms caused by atherosclerosis are in the aortic arch (near where the aorta leaves the heart) and in the part of the aorta that goes to the abdomen.
• carotid artery disease: blockage of the carotid arteries that carry blood to the brain. Blockage of these arteries can result in a transient ischemic attack (TIA) or stroke.

Demographics

It is difficult to determine how many people have atherosclerosis, as it often shows no symptoms until well advanced. The disease is common. Symptoms usually become apparent in people between the ages of 40 and 70. Women show symptoms on average 10 years later than men. This is thought to be due to the protective effects of the female hormone estrogen that is present until women enter menopause around age 50.

Internationally, Great Britain, the Scandinavian countries, and Russia have particularly high rates of coronary artery disease. The disease is less common in the Far East and almost non-existent in most parts of Africa. However, immigrants from countries with low coronary artery disease rates who move to the United States or Europe show rates about equal to the natural-born population, suggesting the development of atherosclerosis is significantly controlled by lifestyle factors (e.g., diet and exercise ).

Causes and symptoms

Many researchers believe that atherosclerosis develops in response to damage to the cells lining the wall of the arteries. Injury can be caused by low-density lipoprotein (LDL) cholesterol (“bad” cholesterol), toxins from cigarette smoke, infectious agents, too much homocysteine in the blood, and hyperglycemia (high blood sugar, a particular problem for people with diabetes and pre-diabetes). Once the cells lining the artery walls are damaged, a cascade effect begins that allows LDL cholesterol and fatty material to build up and form a hard substance called plaque. The presence of plaque on the artery walls both limits the amount of blood that can flow through the artery and increases the turbulence of the blood flow, making the heart work harder. The plaque can also rupture or break free and travel through the circulatory system to block another artery.

Atherosclerosis symptoms are quite variable. Some people with mild to moderate atherosclerosis show symptoms, while others with severe atherosclerosis show no symptoms until they have a heart attach. Common symptoms for atherosclerosis in specific locations were described above.

Despite the absence of symptoms, certain risk factors indicate a higher likelihood of the disease developing. Risk factors include:

• a high level of LDL cholesterol and triglycerides and low level of high density lipoprotein (HDL) HDL cholesterol (“good” cholesterol) in the blood.
• high blood pressure (hypertension) l high blood sugar (diabetes or pre-diabetes)
• smoking
• increasing age

Diagnosis

Physicians can assess risk factors for atherosclerosis with a lifestyle history. Blood pressure measurements and blood tests measuring the amount of cholesterols, triglycerides, and sugar (glucose) in the blood are routinely performed to screen for risk factors. If atherosclerosis is suspected, additional tests may be performed to obtain a diagnosis. These tests include:

• angiogram: an x-ray (radiographic) study of the blood vessels. An angiogram uses a radiopaque substance, or contrast medium, to make the blood vessels visible under x ray.
• echocardiogram: non-invasive imaging test that produces a picture of the heart in motion as it beats; also helpful in determining the extent of a blockage and showing heart and valve damage.
• electrocardiogram (EKG): non-invasive test helps detect abnormalities in heart rhythm and heart health by measuring the electrical activity of the heart
• stress test: an electrocardiogram done while exercising or, for people who cannot exercise, while the heart is stimulated by medication
• Ankle-brachial index: a non-invasive test that compares the blood pressure taken in the ankle to the blood pressure taken in the arm. In a healthy person, the pressures are nearly the same. A lower pressure in the ankle suggests peripheral vascular disease.

Treatment

Treatment falls into three categories: lifestyle changes, drug therapy, and medical procedures. Lifestyle changes involve eating a heart-healthy diet low in saturated (animal) fats and high in fresh fruits, fresh vegetables, and whole grains. This is coupled with calorie reduction if the individual needs to lose weight. Regular moderate exercise (for example, brisk walking for 30 minutes three to five times a week) and quitting smoking also can slow the development of atherosclerosis.

Drug therapy often is used in conjunction with lifestyle changes. It is not a substitute for making lifestyle changes. Several categories of drugs are used to treat atherosclerosis. These include:

• Cholesterol-lowering drugs (statins). These include pravastatin (Pravachol), simvastatin (Zocor), lovastatin (Mevacor, Altocor) fluvastatin (Lescol) and atorvastatin (Lipitor) and rosuvastatin (Crestor).
• Drugs that increase the elimination of cholesterol in feces. These include cholestyramine (Questran, LoCholest, Prevalite) and colestipol (Colestid)
• Dietary supplements. Niacin (vitamin B₃) has been proven to lower LDL cholesterol in high doses (2–6 g daily), although the supplement can have unpleasant side effects, most commonly hot flashes and flushing. Vitamins E, C, and beta-carotene (a form of vitamin A) have antioxidant activity. Their role in controlling cholesterol levels is controversial, and beta-carotene may have harmful side effects, especially in people who smoke. It should be taken only at the direction of a physician.
• Anticoagulant drugs. These drugs, such as aspirin and warfarin (Coumadin), keep the blood from clotting.
• Anti-hypertensives (blood pressure medications). These drugs lower blood pressure and indirectly treat atherosclerosis.

QUESTIONS TO ASK YOUR DOCTOR

• How advanced is my atherosclerosis?
• What kind of treatment do you recommend?
• What kind of side effects can I expect from the drugs you have prescribed?
• Can you provide dietary guidance or refer me to a nutritionist so that I can learn more a heart-healthy diet?
• What is an appropriate level of exercise for me?

Medical procedures for the treatment of atherosclerosis are performed when lifestyle changes and drug therapy fail to control the disease or when blockage of an artery becomes life threatening. Common treatments include:

• Balloon angioplasty. This surgical procedure is done to reopen a partially blocked artery so that blood can flow through it again at a normal rate. A tiny tube (catheter) is threaded through blood vessels to the point of the blockage. The catheter contains a balloon tip that is then expanded to stretch and open the artery.
• Cardiac bypass surgery, also called a coronary artery bypass graft (CABG). In this procedure, a vein or artery from another part of the body is removed and sewn into one of the coronary arteries in order to allow blood to flow around a blockage in the coronary artery.
• Endarterectomy. This procedure surgically removes plaque from an artery. The procedure is often performed on the carotid arteries in the neck that are crucial in supplying blood to the brain.

Nutrition/Dietetic concerns

A heart-healthy diet low in saturated (animal) fats and high in fresh fruits, fresh vegetables, and whole grains is an important key to both preventing and slowing the progression of atherosclerosis. Calorie and weight control are also essential. The American Heart Association has developed many heart-healthy diets and recipes. In individuals with high blood pressure, limiting salt intake is also an important dietary concern.

Prognosis

Atherosclerosis is a common cause of death and disability in the developed world. It is estimated that 11 million Americans have diagnosed coronary artery disease. In addition, atherosclerosis is responsible for 1.5 million heart attacks and 200,000 strokes in the United States each year.

KEY TERMS

Anticoagulant —Medication to prevent clotting proteins and platelets in the blood to be activated to form a blood clot.

Antioxidant —a molecule that prevents oxidation. In the body antioxidants attach to other molecules called free radicals and prevent the free radicals from causing damage to cell walls, DNA, and other parts of the cell

Aorta —The main artery that carries blood from the heart to the rest of the body. The aorta is the largest artery in the body.

Artery —A vessel that carries oxygen-rich blood to the body.

Homocysteine —An amino acid normally found in small amounts in the blood.

Plaque —Fatty material that is deposited on the inside of the arterial wall.

Transient ischemic attack (TIA) —Temporary blockage of blood flow to the brain often resulting in slurred speech, vision disturbances, and loss of balance. The episode is brief and the damage often short-term. Also called a mini-stroke or a warning stroke.

Stroke —Irreversible damage to the brain caused by insufficient blood flow to the brain as the result of a blocked artery. Damage can include loss of speech or vision, paralysis, cognitive impairment, and death.

Prevention

Prevention involves following the lifestyle treatments described above beginning as early in life as possible.

Resources

BOOKS

Myers, Robert. Heart Disease: Everything You Need to Know. Buffalo, NY: Firefly Books, 2004.

Rippe, James M. Heart Disease for Dummies. Indianapolis, IN: Wiley Pub., Inc., 2006.

Sinatra, Stephen T. Reverse Heart Disease Now: Stop Deadly Cardiovascular Plaque Before It's Too Late. Hoboken, NJ: John Wiley & Sons, 2007.

OTHER

“Arteriosclerosis/Atherosclerosis.” Mayo Clinic. June 30, 2006 [cited April 1, 2008]. http://www.mayoclinic.com/health/arteriosclerosisatherosclerosis/DS00525.

Boudi, F. Brian. “Atherosclerosis.” eMedicine.com. August 10, 2006 [cited April 1, 2008]. http://www.emedicinecom/med/topic182.htm.

“What is Atherosclerosis.” National Heart Lung and Blood Institute. undated [cited April 1, 2008]. http://www.nhlbi.nih.gov/health/dci/Diseases/Atherosclerosis/Atherosclerosis_WhatIs.html.

ORGANIZATIONS

American Heart Association, 7272 Greenville Avenue, Dallas, TX, 75231, (800) 242-8721, http://www.americanheart.org.

National Heart Lung and Blood Institute Health Information Center, P.O. Box 30105, Bethesda, MD, 20824-0105, (301) 592-8573; TTY: (240) 629-3255, (240) 629-3246,:[email protected], http://www.nhlbi.nih.gov.

Tish Davidson A. M.

ATHEROSCLEROSIS

DEFINITION

Atherosclerosis (pronounced ath-uh-ro-skluh-RO-siss) is the build-up of a waxy deposit on the inside of blood vessels. Atherosclerosis is a form of arteriosclerosis (pronounced ar-tir-ee-o-skluh-RO-siss). Arteriosclerosis refers to any condition in which the arteries become hard and less flexible. The two terms are often used interchangeably, although it is not really correct to do so.

DESCRIPTION

The arteries are blood vessels that carry blood from the heart to all parts of the body. Arteries are made up of several layers of tissue that are normally soft and pliable. The layers must be able to expand and contract as blood passes through them.

Arteries often become leathery and rigid. When that happens, blood may flow less easily through the arteries. The hardening of arteries is called arteriosclerosis. Many factors can cause arteriosclerosis. Normal aging, high blood pressure, and certain diseases, such as diabetes (see diabetes mellitus entry), are common causes of arteriosclerosis.

Atherosclerosis is a special form of arteriosclerosis. In atherosclerosis, only the inner lining of the artery is affected. Fatty materials deposit on the lining of the artery, forming a larger and larger mass. The mass is usually called a plaque (pronounced PLAK). It becomes more and more difficult for blood to flow through the artery. Eventually the artery may close completely.

The formation of a plaque in an artery can lead to a number of cardiovascular (heart and blood vessel) problems. If the plaque forms in an artery that leads to the heart, it may block the flow of blood to the heart, and a heart attack may occur. If the plaque occurs in an artery that leads from the heart, it may prevent the brain from getting the blood and oxygen it needs. The result is a stroke (see stroke entry).

The plaque may also break off from the artery wall and travel through the bloodstream. It may then block an artery somewhere else in the body, a process known as thrombosis. A thrombosis that blocks an artery in the heart produces a condition known as a coronary thrombosis.

Atherosclerosis can occur anywhere in the body. It can affect arteries of the neck, kidneys, thighs, and arms. In such cases, the interruption of blood flow can produce many medical conditions, such as kidney failure and gangrene (death of tissue).

Atherosclerosis: Words to Know

Angiography:

A method for studying the structure of blood vessels by inserting a catheter into a vein or artery, injecting a dye in the blood vessel, and taking X-ray photographs of the structure.

Arteriosclerosis:

Hardening of the arteries that can be caused by a variety of factors.

Artery:

A blood vessel that carries blood from the heart to other parts of the body.

Cardiovascular:

A term that applies to the heart and blood system.

Catheter:

A long, narrow tube that can be threaded into a patient's vein or artery.

Cholesterol:

A waxy substance produced by the body and used in a variety of ways.

Echocardiogram:

A test that uses sound waves to produce an image of the structure of the heart.

Electrocardiogram:

A test that measures the electrical activity of the heart.

Gangrene:

The death of tissue.

Plaque:

A deposit of fatty materials that forms on the lining of an artery wall.

Radioactive isotope:

A substance that gives off some form of radiation.

Stress test:

An electrocardiogram taken while a patient is exercising vigorously, such as riding a stationary bicycle.

Thrombosis:

The formation of a blood clot.

Triglyceride:

A type of fat.

CAUSES

The exact cause of atherosclerosis is not known. Some researchers consider it to be a natural consequence of aging. But that theory does not explain the actual process of the disease. What is known is that people with certain risk factors are much more likely to develop atherosclerosis than people without those risk factors. Some risk factors are beyond a person's control. For example, some people seem to be genetically more inclined to develop atherosclerosis than other people. Also, the disorder is more common among older than younger people. A person is not able to do much about his or her heredity or the aging process.

Some risk factors, however, are under a person's control. These factors include:

• Cigarette/tobacco smoking. Smoking increases the risk of developing atherosclerosis. It also increases the risk of dying from heart disease. Secondhand smoke may also increase risk.
• High blood cholesterol. Cholesterol is a soft, waxy substance produced naturally by the body. It also occurs in many foods, such as meat, eggs, and other animal products. A certain amount of cholesterol is needed to keep the body healthy. But high levels of cholesterol can increase the risk of atherosclerosis.
• High triglycerides. Triglycerides (pronounced tri-GLIS-uh-ride) are a form of fat. High levels of trigylcerides have been linked with various kinds of artery disease.
• High blood pressure. Blood pressure higher than normal (normal is measured 140 over 90) can make the heart work hard. Both the heart and arteries may become weak (see hypertension entry).
• Physical inactivity. Lack of exercise increases the risk of atherosclerosis.
• Obesity. Excess weight strains the heart. Both heart and arteries may be damaged (see obesity entry). Some risk factors for atherosclerosis that cannot be changed include:
• Heredity. People whose family members have had atherosclerosis are at risk for the disorder.
• Gender. Before age sixty men are more likely to have atherosclerosis than women. After sixty, the risk is equal for men and women.
• Age. The risk for atherosclerosis increases with age.
• Diabetes mellitus. Many diabetics die from heart attacks caused by atherosclerosis.

SYMPTOMS

The symptoms of atherosclerosis vary somewhat depending on the location of a plaque. If the plaque occurs in the arteries of the heart, the patient may experience chest pain, heart attack, or sudden death. A plaque in the brain may lead to sudden dizziness, weakness, loss of speech, or blindness. In arteries of the leg, plaques can lead to cramping and fatigue in the legs when walking. A plaque in the kidneys can cause high blood pressure that is difficult to treat.

DIAGNOSIS

A doctor may be led to suspect atherosclerosis based on any of the symptoms discussed. A variety of tests is available to confirm the diagnosis. For example, an electrocardiogram (pronounced ih-LEK-tro-KAR-dee-o-gram) measures electrical activity of the heart. An abnormal flow of blood to the heart can change this activity. Electrocardiograms are sometimes performed while a patient is taking part in vigorous activity, such as riding a stationary bicycle. Such tests are known as stress tests.

An echocardiogram (pronounced ekko-KAR-dee-o-gram) uses sound waves to study the heart. The sound waves produce a pattern (an echo) as they pass through the heart. The echoes provide information about the heart's structure. Blockages in arteries can sometimes be detected by this method.

Radioactive isotopes can also be used to produce pictures of the heart. A radioactive isotope is a material that gives off some form of radiation. The radioactive isotope is first injected into the patient's bloodstream. It travels through the patient's body, giving off radiation. The radiation can be used to form a picture on a screen, somewhat like an X-ray photograph.

Coronary angiography (pronounced an-gee-AH-graffie) is the most accurate way to diagnose atherosclerosis. In this procedure, a catheter is inserted into a blood vessel in the patient's arm. A catheter is a long, narrow tube that can be pushed through the vein into the patient's heart. A dye is pumped through the catheter into the heart. Then, X-ray pictures are taken of the heart. The dye makes it possible to see structures of the heart in great detail. The presence of plaques can easily be seen.

TREATMENT

Mild cases of atherosclerosis can often be treated with changes in lifestyle. Patients can reduce the amount of fats and cholesterol in their diet, quit smoking, lose weight, and become more physically active. For more serious forms of atherosclerosis, other treatments may be necessary. These include the use of drugs and various forms of surgery.

A class of drugs that is used with atherosclerosis are designed to lower cholesterol. If the amount of cholesterol in the blood is reduced, the chance that plaques will form is also reduced. Aspirin may also be recommended because it tends to cause blood to become thinner.

One form of surgery used with atherosclerosis is angioplasty (pronounced AN-jee-o-PLAS-tee). In angioplasty a catheter tipped with a balloon is inserted into a blood vessel in the patient's thigh or arm. The catheter is then pushed upwards into the artery where a plaque exists. At that point, the balloon is inflated. The balloon pushes on the plaque. It may squeeze the plaque enough to open the artery to its normal size. Blood is then able to again flow through the artery.

Bypass surgery may also be used to treat atherosclerosis. In bypass surgery, the portion of an artery that is blocked by plaque is clamped off. A blood vessel is taken from some other part of the patient's body and inserted just before and just after the section of artery that has been blocked off. Blood is given a new pathway to flow through the body, bypassing the damaged artery. Bypass surgery is completely successful in about 70 percent of all cases and partially successful in another 20 percent.

Alternative Treatment

One focus of alternative treatments for atherosclerosis is diet. Practitioners recommend many of the changes suggested by traditional medicine including reducing the amount of cholesterol and fats eaten. Alternative practitioners also suggest that patients eat more raw and cooked

fish and fresh fruits and vegetables. Onion and garlic are particularly recommended.

A variety of herbs is also recommended to improve the patient's overall health. These herbs include hawthorn, ginger, hot red or chili peppers, yarrow, and alfalfa. Another focus of alternative treatments is helping patients to become more relaxed. In this way, they may feel less stress and experience a reduced blood pressure. Yoga, meditation, and massage are methods for improving relaxation.

PROGNOSIS

Atherosclerosis cannot be cured, but it can be delayed, stopped, and even reversed. One of the most critical steps that a patient can take is to control cholesterol levels. Doctors are now able to detect atherosclerosis in its early stages. That development allows earlier treatment to prevent the most serious complications of the disorder.

PREVENTION

The key to reducing the risk for atherosclerosis is to reduce the risk factors an individual has control over, which includes:

• Eating a healthy diet low in cholesterol and triglycerides. The diet should be high in fruits and vegetables.
• Exercising regularly. Physical activity can lower blood pressure and help control weight.
• Maintaining a desirable body weight.
• Stopping—or never starting—to use tobacco. Even people who smoke can reduce their risk of atherosclerosis by giving up the habit.
• Seeking treatment for hypertension. Hypertension is another name for high blood pressure. High blood pressure is probably a hereditary condition, but it can be brought under control by certain changes in lifestyle. These changes include reducing the amount of sodium and fat in the diet, exercising, learning how to manage stress, giving up smoking, and drinking alcohol in moderation.

FOR MORE INFORMATION

Books

American Heart Association. Guide to Heart Attack Treatment, Recovery, and Prevention. New York: Time Books, 1996.

American Heart Association. Living Well, Staying Well. New York: American Heart Association and American Cancer Association, 1996.

Arnold, Caroline. Heart Disease. New York: Franklin Watts, 1990.

DeBakey, Michael E., and Antonio M. Gotto, Jr. The New Living Heart. Holbrook, MA: Adams Media Corporation, 1997.

Parker, Steve. Heart Disease. New York: Franklin Watts, 1989.

Periodicals

"Landmark Study Shows Heart Disease Prevention Must Start Early." The Nation's Health (March 1997): p. 13.

Morgan, Peggy. "What Your Heart Wishes You Knew about Cholesterol." Prevention (September 1997): p. 96.

Organizations

American Heart Association. National Center. 7272 Greenville Avenue, Dallas, TX 75231–4596. (214) 373–6300. http://www.amhrt.org.

National Heart, Lung, and Blood Institute. P.O. Box 30105, Bethesda, MD 20824–0105. (301) 496–4236. http://www.nhlbi.nih.gov.

ATHEROSCLEROSIS

The most common cause of death and disability in the United States is atherosclerosis, popularly known as "hardening of the arteries."

EPIDEMIOLOGY

Every year atherosclerosis causes about 500,000 deaths nationally, most of these due to heart attack or stroke. There are about 15 million people in the United States suffering from atherosclerosis, and another 60 million are at risk. The factors that put individuals at risk of atherosclerosis include high blood levels of cholesterol and sugar, high blood pressure, and tobacco use. Another important risk factor is a family history of premature atherosclerosis (e.g., a close relative who has had a heart attack or stroke under the age of sixty). In addition to these risk factors, there is accumulating evidence that elevated plasma levels of lipoprotein (a), C-reactive peptide, asymmetric dimethylarginine, and homocysteine also accelerate atherosclerosis, as do obesity, type A personality, and sedentary lifestyle.

PATHOPHYSIOLOGY

Atherosclerosis is thought to be initiated by a "response to injury" of the endothelium (the lining of the blood vessel). Elevated blood levels of cholesterol or glucose, as well as high blood pressure and smoking, cause changes in the endothelium (normally the "teflon" coating of the vessel), which then becomes sticky. It begins to express on its surface "adhesion molecules," which are a bit like cellular velcro. It also expresses "chemokines" which are proteins that attract white blood cells into the vessel. White blood cells (specifically monocytes and T-lymphocytes) begin to stick to the lining of the vessel, and to infiltrate the vessel.

The monocytes migrate into the vessel wall, where they begin to accumulate cholesterol. They become engorged by cholesterol in the vessel wall and become foam cells. As foam cells accumulate in the vessel they distort the overlying endothelium (forming a "fatty streak" in the vessel), and they eventually may even rupture through the endothelial surface. In these areas of endothelial ulceration, platelets adhere to the vessel wall, releasing molecules that stimulate smooth-muscle migration and proliferation. Vascular smooth-muscle cells in the vessel wall proliferate and migrate into the area above the foam cells. The smooth-muscle cells may also become engorged with lipid to form foam cells, and atherosclerotic plaque begins to take form. The plaque grows with the recruitment of more cells, and with the accumulation of matrix made by the cells and cholesterol from the bloodstream. The progression of atherosclerotic plaque is also related to the growth of microscopic vessels into the plaques. The complex plaque typically is characterized by a fibrous cap that overlies a necrotic core composed of cell debris and cholesterol. This core also contains a high concentration of tissue factor, secreted by macrophages. If the plaque ruptures, the exposed tissue factor will cause a blood clot to form, which can lead to a heart attack or stroke.

CLINICAL MANIFESTATIONS

By virtue of its bulk, the complex plaque may limit blood flow. With moderate-sized lesions (e.g., occupying 50% of the cross-sectional area of the inner bore of the vessel), not enough blood can flow through the vessel during states of higher demand. With physical exertion, the inadequate supply of blood may cause chest pain (angina) if the narrowing is in a heart artery, or leg pain (claudication) if the narrowing is in a leg artery. As the lesion becomes larger (e.g., 80 to 90% of the cross-sectional area), it may limit basal blood flow, causing pain at rest (e.g., rest angina).

The complicated plaque is the major cause of acute cardiovascular events (e.g., heart attack and stroke). Hemorrhage into the plaque (secondary to spontaneous rupture of small vessels supplying the lesion) can cause rapid expansion of the plaque. Alternatively, rupture of the plaque releases the tissue factor in the necrotic core, which causes local clot formation and even occlusion of the vessel, leading to heart attack, stroke, or gangrene of the leg, depending upon what vessels are effected. Microscopic examination of the ruptured plaque generally reveals that the plaque is inflamed. Infection of the plaque by bacteria or viruses may play a role in the inflammation and rupture of plaques.

PREVENTION OF ATHEROSCLEROSIS

The best medical strategy for this disease is prevention through aggressive modification of risk factors. Regular physical activity; reduction of cholesterol, blood sugar, and blood pressure; and cessation of tobacco use are known to modify the progression of disease and reduce morbidity and mortality. In addition to removing or reducing risk factors, recent work indicates that enhancing endothelial function can also favorably influence the course of disease.

ROLE OF THE ENDOTHELIUM

The endothelium is the lining of the blood vessel. It produces a panoply of paracrine factors that effect vessel tone and structure. Possibly the most important of these is endothelium-derived nitric oxide (NO). NO is derived from the metabolism of L-arginine to L-citrulline and NO by the enzyme NO synthase. NO is the most potent endogenous vasodilator known, and it exerts its actions in the same way as nitroglycerine, a medicine taken by people to relieve angina.

NO also inhibits clot formation, and adherence of monocytes to the vessel. It also inhibits the growth of vascular smooth-muscle cells. By exerting these effects, NO, and a similarly acting molecule, prostacyclin, may be the body's self-defense against atherosclerosis.

Risk factors, such as high cholesterol, high blood pressure, high blood glucose, and tobacco smoke, impair endothelial function and reduce NO and prostacyclin synthesis or activity, thereby contributing to the process of atherosclerosis. Restoration of normal function of the endothelium can relieve symptoms, and may even slow the progression of atherosclerosis.

John P. Cooke

(see also: Blood Lipids; Blood Pressure; Cardiovascular Diseases; Coronary Artery Disease; Diabetes Mellitus; HDL Cholesterol; LDL Cholesterol; Stroke; Smoking Behavior; Smoking Cessation )

Bibliography

Berliner, J. A.; Navab, M.; Fogelman, A. M. et al. (1995). "Atherosclerosis: Basic Mechanisms. Oxidation, Inflammation, and Genetics." Circulation 91: 2488–2496.

Cooke, J. P., and Dzau, V. J. (1997). "Nitric Oxide Synthase: Role in the Genesis of Vascular Disease." Annual Reviews of Medicine 48:489–509.

Ross, R. (1997). "Cellular and Molecular Studies of Atherosclerosis." Atherosclerosis 13:S3–S4.