Atherosclerosis and coronary artery disease

Atherosclerosis is the buildup of plaque or cholesterol, lipids and other material in the arteries. Eventually, this buildup causes narrowing of the arteries.

Coronary artery disease (CAD) is atherosclerosis of one or more coronary arteries, the blood vessels that supply the heart muscle with blood. Coronary artery disease is the major cause of death from cardiovascular disease (any disease of the heart and blood vessels). Cardiovascular disease is the leading cause of death in the United States.

Other types of cardiovascular disease include:

hypertension (high blood pressure)
stroke (a condition caused by a lack of blood flow to the brain, from either a blood clot or bleeding)
rheumatic heart disease (heart disease that results from rheumatic fever, a condition that may develop from an untreated streptococcal infection)

Anatomy
The heart muscle receives blood from two arteries: the left and right coronary arteries.
The left coronary artery has two major branches, the left anterior descending and the circumflex artery. These arteries generally supply the left atria (the upper left chamber) and ventricle (the lower left chamber) of the heart.

The right coronary artery also has two main branches, the right posterior descending and the acute marginal branch. These arteries generally supply the right atria (the upper right chamber) and ventricle (the lower right chamber) of the heart. The right coronary artery also supplies important portions of the inferior ventricular septum (the portion of muscle between the ventricles) and often the posterior walls.

The coronary arteries have three layers: the adventitia (the outermost layer), the media (the middle layer) and the intima (the innermost layer).


Causes/associated factors
The development of atherosclerosis is a complex, ongoing process that's not completely understood. It's thought that the innermost layer of a particular artery becomes injured. Then, lipoproteins (a chemical compound in the blood made of fat and protein) and an inflammatory process cause a buildup on the arterial wall called plaque, which impedes blood flow in the artery. Blood clots may develop at the plaque site, which may lead to a heart attack or stroke.
Some risk factors for developing atherosclerosis can't be controlled, such as aging, having a family history of heart disease, and being male. (After age 60, however, men and women have the same risk.) Others risk factors may be within your control, such as:

high cholesterol (especially high LDL or "bad" cholesterol)
high triglyceride levels
high blood pressure
diabetes and insulin resistance
smoking
obesity
lack of physical activity
Elevated blood levels of certain factors known as inflammatory or thrombosis markers -- including C-reactive protein, homocysteine, lipoprotein a and clotting factors (such as fibrinogen) -- may also be associated with atherosclerosis. More research must be done to determine the significance of these markers and their potential use in screening those at high risk for CAD.


Signs/symptoms
Up to one-third of all people who have CAD experience no symptoms. If symptoms appear, they may include:
chest pain
fatigue
shortness of breath
nausea or vomiting
weakness
sweating
pain that radiates to the arm, jaw, back, shoulder or neck
rapid or irregular heartbeat
indigestion
for women, breast pain
In severe cases, CAD may cause a heart attack (insufficient blood supply to the heart) or cardiac arrest (temporary or permanent cessation of heartbeat).


Diagnosis
The doctor will review your medical history and do a physical exam. To determine the presence and extent of CAD, other heart disease or circulatory problems, you may also need one or more of the following tests:
electrocardiogram (ECG, a recording of the electrical activity of the heart)

blood and urine tests

chest X-ray

exercise stress test with ECG monitoring and, sometimes, radioactive thallium (a substance that will appear on an X-ray to help doctors diagnose impaired coronary blood flow)

medication stress test, if you're unable to walk

echocardiogram (using sound waves to study the heart and surrounding tissues), sometimes in combination with an exercise stress test

coronary angiogram (an imaging technique that allows the study of blood vessels through injection of contrast dye, a substance used with various imaging techniques)

electrophysiologic heart studies (tests that use a catheter threaded into the heart to detect and map heart irregular heartbeats)

electron beam tomography (EBT, a computed tomography scan of the heart that can detect calcium deposits on the coronary arteries)

contrast CT scan of the heart, a new technique that appears to be promising

Treatment
Treatment for CAD usually involves a combination of lifestyle modifications and medications.
Lifestyle modifications
To minimize your heart's workload, maintain a healthy weight. If you're overweight, lose the excess pounds. Your doctor may also recommend a diet high in fiber and low in fat, cholesterol and sodium.

Weight loss and dietary benefits: Obesity increases the risk of coronary artery disease, high blood pressure and diabetes. Maintaining an optimal weight puts less stress on your heart. Low-fat, low-cholesterol, low-sodium diets have been shown to lower blood pressure and cholesterol, as well as slow the progression of atherosclerosis.

Weight loss and dietary risks: Changing your lifelong eating habits can be difficult to do and maintain. You must be committed to making the change. You may need to learn about nutrition as well.
Work with your doctor to coordinate a safe aerobic exercise program.

Exercise benefits: Exercise improves insulin resistance and increases HDL or "good" cholesterol. Aerobic exercise and getting in shape will condition your muscles, lower your heart rate, and lower the oxygen demands placed on your heart. It can decrease your symptoms and improve your quality of life. It can also decrease the risk of dying from heart conditions. Some exercise is better than none at all. Always check with your doctor before beginning an exercise program.

Exercise risks: Only about half of all people who begin exercise programs continue for more than six months. Improper form may lead to injuries. Isometric exercise (such as weight training) can raise blood pressure and increase oxygen demand on the heart.
Learn to manage your stress.

Stress management benefits: Biofeedback and other relaxation techniques can help control or reduce stress and anger, which have been shown to trigger angina as well as other heart-related events. Reducing stress may help you smoke less and resist the temptation to eat "comfort food."

Stress management risks: Studies give mixed results on the relationship between psychological interventions and heart-related events.
If you smoke, quit.

Smoking cessation benefits: Smoking worsens atherosclerosis, increases the heart's demand for oxygen, and can make angina more severe. Quitting smoking reduces the risk of dying from heart disease.

Smoking cessation risks: Smoking can be a difficult habit to break.
Medications
Various medications may be prescribed to treat CAD:

Beta blockers slow heart rate and lower blood pressure.

Beta blocker benefits: Beta blockers reduce the amount of oxygen required by the heart and decrease the heart's workload.

Beta blocker risks: Side effects include dizziness. Beta blockers aren't recommended for people who have certain respiratory problems, such as asthma. Other possible side effects may include drowsiness, fatigue, lower libido or, for men, erectile dysfunction (impotence).
Nitrates (such as isosorbide and nitroglycerin) open the coronary arteries so more blood can flow to the heart muscle. Nitrates also open other vessels, which lowers blood pressure and eases the heart's workload.

Nitrate benefits: Nitrates relieve chest pain quickly and can be taken under the tongue (sublingual), through a spray (translingual), or held between the cheek and gum (intrabuccal). Oral capsules are also available. For maintenance therapy, cream can be applied to the skin or a skin patch can be worn.
Note: If the pain doesn't respond to nitroglycerin within 15 minutes, seek emergency medical attention.


Nitrate risks: After you take a dose of nitroglycerin under the tongue, you may get a headache. The headaches usually subside with continued use. Other possible side effects of nitrates (taken in any fashion) include flushing, a pulsating sensation in the head, dizziness upon standing and, sometimes, nausea and vomiting. If you notice these side effects, sit up in bed or a chair. Nitrates can also cause reflex tachycardia (when the heartbeat accelerates in response to a stimulus outside the heart). Men who take certain erectile dysfunction medications should not take nitrates. Discuss the risk of any potential medication interactions with your doctor.
Antiplatelet medications help prevent blood from clotting. For example, low doses of aspirin are often prescribed as a preventive measure for those at risk for heart disease (including men older than age 40 and women past menopause). If you're unable to take aspirin, warfarin or clopidogrel may be prescribed.

Antiplatelet benefits: Taking antiplatelet medications may prevent a heart attack.

Antiplatelet risks: Antiplatelet medications may increase the risk of bleeding.
Calcium channel blockers lower blood pressure and open coronary arteries.

Calcium channel blocker benefits: Calcium channel blockers decrease the heart's workload, reduce pressure in the arteries by widening them, and then increase the amount of oxygen delivered to the heart.

Calcium channel blocker risks: Some calcium channel blockers are dangerous for people who have heart failure or had a heart attack.
The most common side effects of calcium channel blockers are fatigue and leg swelling, but side effects vary depending on the specific medication taken. Contact your doctor if you have any of these symptoms. If other medications are prescribed, discuss the risk of any potential medication interactions with your doctor. Since alcohol may cause an excessive drop in blood pressure, it's best to avoid alcohol when taking calcium channel blockers.

Angiotensin-converting enzyme (ACE) inhibitors lower blood pressure, slow the progression of heart failure, and promote long-term improvement in heart function.

ACE inhibitor benefits: ACE inhibitors can delay the development of heart failure for people at high risk.

ACE inhibitor risks: Side effects may include dizziness, cough, swelling of the face and lips, and worsening of renal insufficiency. Angiotensin receptor blockers (ARBs) may be prescribed for people who are unable to take ACE inhibitors.
Lipid-lowering therapy is another important element of CAD therapy. Medications that may be recommended to reduce cholesterol include statins, bile-acid binding resins, fibrates and an intestinal cholesterol transferase inhibitor (such as Ezetimibe, for example).

Statins block the enzyme that triggers the liver to make cholesterol. They include Lovastatin (Mevacor, for example), pravastatin (Pravachol, for example), rosuvastatin (Crestor, for example) and simvastatin (Zocor, for example). Examples of newer statins include fluvastatin (Lescol, for example) and atorvastatin (Lipitor, for example). Statins are often the first medication of choice to lower cholesterol levels, particularly for people who have heart disease or diabetes.

Statin benefits: Statins lower bad (LDL) cholesterol levels, lower triglyceride levels, and raise good (HDL) cholesterol levels. If you have heart disease, they can reduce the risk of having a heart attack.

Statin risks: These medications may cause myositis (inflammation of the muscle tissue) and the development of higher levels of certain enzymes in the liver. Side effects may also include aching joints and muscle pain.
Bile-acid binding resins work by attaching to bile, which is made from cholesterol. Cholestyramine (Questran, for example) and colestipol hydrochloride (Colestid, for example) are often used to prevent high cholesterol or reduce mildly elevated LDL levels.

Bile-acid binding resins benefits: Resins can reduce cholesterol levels and may reduce the risk of having a heart attack.

Bile-acid binding resins risks: Resins aren't as effective as statins and are no longer first-line agents. Resins can also interact with other medications. Side effects may include gastrointestinal symptoms such as heartburn and constipation. Bile-acid binding resins are often prescribed along with other medications.
Fibrates are often prescribed to lower triglyceride levels. Gemfibrozil (Lopid, for example) and fenofibrate (Tricor, for example) are medications in this category.

Fibrates benefits: Fibrates lower triglyceride levels. If you have heart disease, they may reduce your risk of having a heart attack.

Fibrates risks: Fibrates have varied effects on LDL levels. Side effects of fibrates may include muscle pain and, rarely, muscle and kidney damage.
Ezetimibe (Zetia, for example), is a new cholesterol-lowering medication that prevents the intestine from absorbing cholesterol. Research is currently underway on another new medication to raise HDL levels -- torcetrapib. This medication blocks the protein known to lower HDL.

Surgical and nonsurgical procedures
Coronary artery bypass grafting (CABG, a surgical procedure) or angioplasty (a nonsurgical procedure) may be recommended if you have CAD or severe or unstable angina (a condition in which the heart muscle is deprived of oxygen, causing chest pain).

Coronary artery bypass graft surgery is open-heart surgery. Before surgery, the blocked area of the coronary arteries is first identified through coronary arteriography (injecting contrast dye into the arteries for X-ray imaging) during cardiac catheterization (passing a special tube into the heart through an artery in the arm or leg). The procedure involves taking a blood vessel from another part of the body or using a synthetic tube to direct blood flow around a coronary artery blockage. Several blood vessels, or "grafts," may be used, depending on the number of blockages.

CABG benefits: CABG improves blood flow to the heart, which decreases or eliminates anginal pain. People who have left coronary artery blockages may get better results with CABG vs. angioplasty. Studies have shown that people who have diabetes fare better with CABG than with percutaneous transluminal coronary angioplasty (PTCA, see below). Newer techniques are available that are less invasive than traditional open-heart surgery.

CABG risks: The recovery time is longer than PTCA. If you're older than age 70, have had the procedure before, or have other major health problems, the risk for complications increases. Common surgical risks include possible anesthesia reactions, bleeding and infection. Rarely, the complications may be fatal.
Angioplasty (also known as percutaneous transluminal coronary angioplasty, PTCA, balloon dilation and balloon angioplasty) is a nonsurgical option. As with CABG, the blocked area of the coronary artery is first identified through coronary arteriography during cardiac catheterization. Then, a small catheter with a balloon at its tip is threaded through a vessel in the groin to the blocked artery in the heart. The balloon is inflated, usually several times, to help widen the artery and then the balloon is removed. Stents (metal mesh tubes that hold vessels open) may be used to help prevent residual and future narrowing in the artery. Long-term medication therapy is typically prescribed. For most people, this involves aspirin and another antiplatelet medication (such as clopidogrel), and a statin (a cholesterol-lowering medication), a beta blocker and an ACE inhibitor.

Angioplasty benefits: Angioplasty can improve blood flow through the coronary arteries. It's less invasive than coronary artery bypass surgery, and the recovery time is faster. General anesthesia can be avoided, and removing a blood vessel from the leg or chest isn't necessary. Angioplasty may be an option for people considering bypass surgery, as well as those who've already had bypass surgery.

Angioplasty risks: About 30 to 40 percent of cleared blockages return within six months. A repeat angioplasty is often successful. The rate of repeat blockages after stent placement may be as low as 15 to 20 percent. It's not as successful in reopening vein grafts used in CABG. A medication-coated stent designed to further reduce a recurrent blockage was approved by the U.S. Food and Drug Administration (FDA) in 2003. Although side effects associated with these stents present a slight risk, original problems with the stents have largely been resolved through the use of medication and meticulous implantation technique. Another medication-coated stent is showing promising results in clinical trials.
Other risks of angioplasty may include:


an allergic reaction to the dye
excessive bleeding that may require treatment or a transfusion
spasm of the coronary artery
damage to the coronary artery that requires emergency bypass surgery
interrupted blood flow to the heart or area where the catheter is inserted, causing a heart attack
stroke
Rarely, complications of angioplasty may be fatal.

Atherectomy is a nonsurgical procedure in which plaque is removed from the arteries. It may be beneficial to insert a stent when removing calcified plaque or for difficult blockages, but research on the long-term benefit doesn't support this.

Other treatments are currently being studied, and new procedures may be considered when conventional methods are unsuccessful, not possible or not tolerated. For example, transmyocardial revascularization is a surgical procedure that users lasers to open tiny holes in the heart muscle to improve blood flow. Other possible treatments include gene therapy and stem-cell injections.


Complications
As atherosclerosis progresses, plaque accumulates and a composite of lipids, inflammatory cells and calcium damages the blood vessel wall. This increases the risk for plaque rupture, which can result in unstable angina, a heart attack or even sudden death. CAD may cause cardiomyopathy, a condition in which the heart muscle enlarges and weakens from inadequate blood flow to the heart muscle. Cardiomyopathy can lead to heart failure (an inadequate pumping of blood to the rest of the body).

Pregnancy-specific information
Coronary artery disease is rare in pregnancy. As maternal age increases, however, so can the risk factors associated with CAD. If your doctor suspects you have CAD, a stress echocardiogram may be done.
If you're diagnosed with heart disease, consult a cardiologist (a heart specialist) who can coordinate care with your primary doctor throughout the pregnancy. The increased demands of pregnancy on your body may aggravate your condition and pose treatment challenges. Increased blood volume, blood pressure changes, fluid retention and possible pregnancy complications may also influence your heart's stability.

Throughout the pregnancy, your doctor will assess the risk of any angina medications to both you and your baby. Sometimes, the need for medication outweighs the risks.


Senior-specific information
The risk of developing heart disease increases with age. Although CAD is the most frequent cause of death among older adults, the symptoms often associated with CAD may not be as common among older adults. Shortness of breath during exertion is a more typical symptom of CAD for elderly adults than chest pain from angina. Attributing atypical complaints, such as shoulder or back pain or indigestion, to other conditions may delay needed care. In addition, the risk of sudden cardiac death as the first symptom of CAD also increases with age.
Medication choice and dose is influenced by:

age-related changes that affect cardiovascular response to medication
increased likelihood for interactions with other medications
how the medication will be absorbed
how long the medication will be effective
how the medication is taken
how the medication is excreted
Older adults may also be more sensitive to medication side effects, particularly a tendency for lightheadedness or dizziness when getting up from a bed or chair (a condition known as orthostatic hypotension).


Prevention
Work with your doctor to identify and treat individual risk factors or underlying conditions. Consider the following suggestions to reduce your risk of heart disease:
If you smoke, quit.

Exercise regularly, and maintain a normal weight for your age and height.

If you're overweight, ask your doctor for help creating a weight loss plan.

Reduce stress levels.

Avoid excessive alcohol (no more than 2 to 3 ounces a day) and caffeine.

Eat a diet high in fiber and low in fat, cholesterol and sodium.

If you have high cholesterol or high blood pressure, ask your doctor about screening for diabetes.

Ask your doctor about vitamin supplements. Their benefit hasn't been supported in studies, but your doctor may recommend them anyway.