What is coronary artery disease?

Coronary artery disease (CAD) is atherosclerosis (plaque in artery walls) of the inner lining of the blood vessels that supply blood to the heart. A similar term, arteriosclerosis which means hardening or stiffening of the arteries is sometimes interchanged with atherosclerosis by some authors. CAD is a common form of heart disease and is a major cause of illness and death. CAD begins when hard cholesterol substances (plaques) are deposited within a coronary artery. The coronary arteries arise from the aorta, which is adjacent to the heart. The plaques narrow the internal diameter of the arteries (Figure1) which may cause a tiny clot to form which can obstruct the flow of blood to the heart muscle (Figure 2). Symptoms of CAD include:

1. chest pain (angina pectoris) from inadequate blood flow to the heart;
2. heart attack (acute myocardial infarction), from the sudden total blockage of a coronary artery; or
3. sudden death, due to a fatal rhythm disturbance.

Picture of an artery clogged with cholesterol plaque Heart Attack illustration - Coronary Artery Disease Screening Tests

What is the purpose of screening tests for CAD?

In many patients, the first symptom of CAD is myocardial infarction or sudden death, with no preceding chest pain as a warning. For this reason, doctors perform screening tests to detect signs of CAD before serious medical events occur so the tests are designed to detect plaque (Figure 1) before a coronary artery becomes completely blocked (Figure 2). Screening tests are of particular importance for patients with risk factors for CAD. These risk factors include a family history of CAD at relatively young ages, an abnormal serum cholesterol profile, cigarette smoking, elevated blood pressure (hypertension), and diabetes mellitus.

What are common initial screening tests for CAD?

EKG (Electrocardiogram)

An electrocardiogram (EKG) is usually the first and most simple test used to look for any CAD signs. Unless the patient is actively having a heart attack (myocardial infarction) which is often seen as an electrical change in the heart rhythm (ST segment elevation), the EKG may show electrical changes such as ST depressions or Q waves that suggest the patient has CAD or CAD with signs of a previous heart attack. An EKG often encourages the physician to proceed with initial screening test(s).

Initial screening for CAD commonly involves stressing the heart under controlled conditions. These stress tests are able to detect the presence of flow-limiting blockages in the coronary arteries, generally in the range of at least a 50% reduction in the diameter of at least one of the three major coronary arteries. There are two basic types of stress tests; those that involve exercising the patient to stress the heart (exercise cardiac stress tests), and those that involve chemically stimulating the heart directly to mimic the stress of exercise (physiologic stress testing). Physiologic stress testing can be used for patients who are unable to exercise.

Exercise cardiac stress test (treadmill stress test or ECST)

Exercise cardiac stress testing (ECST) is the most widely used cardiac stress test. The patient exercises on a treadmill according to a standardized protocol, with progressive increases in the speed and elevation of the treadmill (typically changing at three minute intervals). During the ECST, the patient's electrocardiogram (EKG), heart rate, heart rhythm, and blood pressure are continuously monitored. If a coronary arterial blockage results in decreased blood flow to a part of the heart during exercise, certain changes (for example, ST segment depressions) may be observed in the EKG, as well as in the response of the heart rate and blood pressure.

The accuracy of the ECST in predicting significant CAD is variable, depending in part on the "pre-test likelihood" of CAD (also known as Bayes' theorem). In a patient at high risk for CAD (for example, advanced age, multiple coronary risk factors), an abnormal ECST is very predictive of the presence of CAD (over 90% accurate). However, a relatively normal ECST may not reflect the absence of significant disease in a patient with the same risk factors. Conversely, in a low-risk patient, a normal ECST is very predictive of the absence of significant CAD (over 90% accurate), but an abnormal test may not reflect the true presence of CAD (so-called "false-positive ECST"). The ECST may either miss the presence of significant CAD, or be a false-positive test, due to a variety of cardiac circumstances, which may include:

1. An abnormal EKG at rest, which may be due to abnormal serum electrolytes, abnormal cardiac electrical conduction, or certain medications, such as digitalis;
2. Heart conditions not related to CAD, such as mitral valve prolapse or hypertrophy (increased size) of the heart; or
3. An inadequate increase in the heart rate and/or blood pressure during exercise.

What if the initial ECST does not clarify the diagnosis?

When the doctor determines that the results of the ECST do not accurately reflect the presence or absence of significant CAD, additional tests are often used to clarify the condition. These additional options include radionuclide isotope injection and ultrasound of the heart (stress echocardiography) during the stress test.

Radionuclide stress test

Radionuclide stress testing involves injecting a radioactive isotope (typically thallium or cardiolite) into the patient's vein after which an image of the patient's heart becomes visible with a special camera. The radioactive isotopes are absorbed by the normal heart muscle. Nuclear images are obtained in the resting condition, and again immediately following exercise. The two sets of images are then compared. During exercise, if a blockage in a coronary artery results in diminished blood flow to a part of the cardiac muscle, this region of the heart will appear as a relative "cold spot" on the nuclear scan. This cold spot is not visible on the images that are taken while the patient is at rest (when coronary flow is adequate). Radionuclide stress testing, while more time-consuming and expensive than a simple ECST, greatly enhances the accuracy in diagnosing CAD.

Learn more about: cardiolite

Learn more about: cardiolite

Stress echocardiography

Another supplement to the routine ECST is stress echocardiography. During stress echocardiography, the sound waves of ultrasound are used to produce images of the heart at rest and at the peak of exercise. In a heart with normal blood supply, all segments of the left ventricle (the major pumping chamber of the heart) exhibit enhanced contractions of the heart muscle during peak exercise. Conversely, in the setting of CAD, if a segment of the left ventricle does not receive optimal blood flow during exercise, that segment will demonstrate reduced contractions of heart muscle relative to the rest of the heart on the exercise echocardiogram. Stress echocardiography is very useful in enhancing the interpretation of the ECST, and can be used to exclude the presence of significant CAD in patients suspected of having a "false-positive" ECST.

What if patients are unable to exercise adequately for an ECST?

Many patients are unable to exercise maximally for stress testing due to a variety of conditions including arthritis, severe lung disease, severe cardiac disease, orthopedic conditions, and diseases of the nervous system. In such patients, pharmacological stress testing is often employed.

Pharmacologic stress test

During a pharmacologic stress test, certain medications are administered which stimulate the heart to mimic the physiologic effects of exercise. One of these medications is dobutamine, which is similar to adrenaline. Dobutamine is carefully administered to gradually increase the heart rate and strength of the contractions of the heart muscle. Simultaneously, echocardiography or radionuclide imaging is performed.

Learn more about: dobutamine

Learn more about: dobutamine

Alternatively, a medicine called adenosine is administered, which simulates the physiology of the coronary artery circulation during exercise. Adenosine is combined with radionuclide isotope imaging to provide a very accurate test for the detection of significant CAD. A newer agent, regadenoson (Lexiscan), is often used as it seems to be better tolerated. Pharmacological stress testing is commonly performed in patients who are thought to be at high risk for significant CAD and who are scheduled for major non-cardiac surgical procedures. These patients are often unable to perform exercise stress testing due to the underlying condition for which they require surgery. In this setting, pharmacological stress testing is invaluable in assessing the cardiac risk of patients prior to surgery.

Learn more about: Lexiscan

Learn more about: Lexiscan

Are there other tests for CAD that are noninvasive?

CT scanning

A new noninvasive test for the detection of CAD is electron beam computerized tomography (EBCT), or calcium scoring. Unlike the above mentioned stress tests that measure the heart's physiology, EBCT is designed to measure calcium deposits in the coronary arteries.

In patients with CAD, the plaques which make up the blockages contain significant amounts of calcium, which can be detected with the CT scanner and the amount of blockage is calculated by calcium scoring. This test will identify calcium in blockages as mild as 10%-20%, which would not be detected by standard physiological testing. When such mild blockages are detected, however, the only recommended therapy is risk factor modification (cholesterol lowering and cessation of smoking if applicable), and adjunctive use of aspirin and certain vitamins; such therapy would be advised in all patients with risk factors for CAD, regardless of the results of any noninvasive tests.

Learn more about: aspirin

Calcium scoring may be very helpful in convincing patients to change their lifestyle or take their medicines, as a score that is not zero implies that the blockage process is starting, and likely will progress unless lifestyle changes are made. It is important to realize that calcification is a function of age, and in younger patients (men under 50, women under 60) the calcium score is less helpful when low.

A more elaborate modality is CT angiography (ultrafast CT). This is a non-invasive (no catheter involved) form of angiogram, but still involves dye exposure and radiation, and is less precise than a coronary angiogram. This is still a rather new modality, and its role is still being defined.

What is the most accurate method of defining CAD?

The "gold standard" for the evaluation of CAD remains the coronary angiogram. Coronary angiography can be used to identify the exact location and severity of CAD; it is described below.

Coronary angiography

During a coronary angiogram (also termed a coronary catheterization), a small catheter (a thin hollow tube with a diameter of 2-3 mm) is inserted through the skin into an artery usually in either the groin or the arm. Guided with the assistance of a fluoroscope (a special X-ray viewing instrument), the catheter is then advanced to the opening of the coronary arteries, the blood vessels supplying blood to the heart. Next, a small amount of radiographic contrast (a solution containing iodine, which is easily visualized with X-ray images) is injected into each coronary artery. The images that are produced are called the angiogram.

Angiographic images accurately reveal the extent and severity of all coronary arterial blockages. Coronary angiography is performed with the use of local anesthesia and intravenous sedation, and is generally not terribly uncomfortable. The procedure takes approximately 20 to 30 minutes. After the procedure, the catheter is removed and the artery in the leg or arm is sutured, "sealed," or treated with manual compression to prevent bleeding. There is a small risk of serious complications from coronary angiography, as it is an "invasive" test, but in the hands of experienced physicians, this risk is quite small (well below one per cent). In appropriate patients, the therapeutic information learned from the angiogram is far more valuable than the relatively small risk of the procedure.

For patients with severe angina or heart attack (myocardial infarction), or those who have markedly abnormal noninvasive tests for CAD, the angiogram also helps the doctor select the optimal treatment, which may include medications, balloon angioplasty, coronary stent placement, or coronary bypass surgery. The coronary angiogram is the only test which allows the precise quantification of the extent and severity of CAD to optimally make these treatment decisions.

Picture of a coronary ballooon angiogram

What is the purpose of screening tests for CAD?

In many patients, the first symptom of CAD is myocardial infarction or sudden death, with no preceding chest pain as a warning. For this reason, doctors perform screening tests to detect signs of CAD before serious medical events occur so the tests are designed to detect plaque (Figure 1) before a coronary artery becomes completely blocked (Figure 2). Screening tests are of particular importance for patients with risk factors for CAD. These risk factors include a family history of CAD at relatively young ages, an abnormal serum cholesterol profile, cigarette smoking, elevated blood pressure (hypertension), and diabetes mellitus.

What are common initial screening tests for CAD?

EKG (Electrocardiogram)

An electrocardiogram (EKG) is usually the first and most simple test used to look for any CAD signs. Unless the patient is actively having a heart attack (myocardial infarction) which is often seen as an electrical change in the heart rhythm (ST segment elevation), the EKG may show electrical changes such as ST depressions or Q waves that suggest the patient has CAD or CAD with signs of a previous heart attack. An EKG often encourages the physician to proceed with initial screening test(s).

Initial screening for CAD commonly involves stressing the heart under controlled conditions. These stress tests are able to detect the presence of flow-limiting blockages in the coronary arteries, generally in the range of at least a 50% reduction in the diameter of at least one of the three major coronary arteries. There are two basic types of stress tests; those that involve exercising the patient to stress the heart (exercise cardiac stress tests), and those that involve chemically stimulating the heart directly to mimic the stress of exercise (physiologic stress testing). Physiologic stress testing can be used for patients who are unable to exercise.

Exercise cardiac stress test (treadmill stress test or ECST)

Exercise cardiac stress testing (ECST) is the most widely used cardiac stress test. The patient exercises on a treadmill according to a standardized protocol, with progressive increases in the speed and elevation of the treadmill (typically changing at three minute intervals). During the ECST, the patient's electrocardiogram (EKG), heart rate, heart rhythm, and blood pressure are continuously monitored. If a coronary arterial blockage results in decreased blood flow to a part of the heart during exercise, certain changes (for example, ST segment depressions) may be observed in the EKG, as well as in the response of the heart rate and blood pressure.

The accuracy of the ECST in predicting significant CAD is variable, depending in part on the "pre-test likelihood" of CAD (also known as Bayes' theorem). In a patient at high risk for CAD (for example, advanced age, multiple coronary risk factors), an abnormal ECST is very predictive of the presence of CAD (over 90% accurate). However, a relatively normal ECST may not reflect the absence of significant disease in a patient with the same risk factors. Conversely, in a low-risk patient, a normal ECST is very predictive of the absence of significant CAD (over 90% accurate), but an abnormal test may not reflect the true presence of CAD (so-called "false-positive ECST"). The ECST may either miss the presence of significant CAD, or be a false-positive test, due to a variety of cardiac circumstances, which may include:

1. An abnormal EKG at rest, which may be due to abnormal serum electrolytes, abnormal cardiac electrical conduction, or certain medications, such as digitalis;
2. Heart conditions not related to CAD, such as mitral valve prolapse or hypertrophy (increased size) of the heart; or
3. An inadequate increase in the heart rate and/or blood pressure during exercise.

What if the initial ECST does not clarify the diagnosis?

When the doctor determines that the results of the ECST do not accurately reflect the presence or absence of significant CAD, additional tests are often used to clarify the condition. These additional options include radionuclide isotope injection and ultrasound of the heart (stress echocardiography) during the stress test.

Radionuclide stress test

Radionuclide stress testing involves injecting a radioactive isotope (typically thallium or cardiolite) into the patient's vein after which an image of the patient's heart becomes visible with a special camera. The radioactive isotopes are absorbed by the normal heart muscle. Nuclear images are obtained in the resting condition, and again immediately following exercise. The two sets of images are then compared. During exercise, if a blockage in a coronary artery results in diminished blood flow to a part of the cardiac muscle, this region of the heart will appear as a relative "cold spot" on the nuclear scan. This cold spot is not visible on the images that are taken while the patient is at rest (when coronary flow is adequate). Radionuclide stress testing, while more time-consuming and expensive than a simple ECST, greatly enhances the accuracy in diagnosing CAD.

Learn more about: cardiolite

Learn more about: cardiolite

Stress echocardiography

Another supplement to the routine ECST is stress echocardiography. During stress echocardiography, the sound waves of ultrasound are used to produce images of the heart at rest and at the peak of exercise. In a heart with normal blood supply, all segments of the left ventricle (the major pumping chamber of the heart) exhibit enhanced contractions of the heart muscle during peak exercise. Conversely, in the setting of CAD, if a segment of the left ventricle does not receive optimal blood flow during exercise, that segment will demonstrate reduced contractions of heart muscle relative to the rest of the heart on the exercise echocardiogram. Stress echocardiography is very useful in enhancing the interpretation of the ECST, and can be used to exclude the presence of significant CAD in patients suspected of having a "false-positive" ECST.

What if patients are unable to exercise adequately for an ECST?

Many patients are unable to exercise maximally for stress testing due to a variety of conditions including arthritis, severe lung disease, severe cardiac disease, orthopedic conditions, and diseases of the nervous system. In such patients, pharmacological stress testing is often employed.

Pharmacologic stress test

During a pharmacologic stress test, certain medications are administered which stimulate the heart to mimic the physiologic effects of exercise. One of these medications is dobutamine, which is similar to adrenaline. Dobutamine is carefully administered to gradually increase the heart rate and strength of the contractions of the heart muscle. Simultaneously, echocardiography or radionuclide imaging is performed.

Learn more about: dobutamine

Learn more about: dobutamine

Alternatively, a medicine called adenosine is administered, which simulates the physiology of the coronary artery circulation during exercise. Adenosine is combined with radionuclide isotope imaging to provide a very accurate test for the detection of significant CAD. A newer agent, regadenoson (Lexiscan), is often used as it seems to be better tolerated. Pharmacological stress testing is commonly performed in patients who are thought to be at high risk for significant CAD and who are scheduled for major non-cardiac surgical procedures. These patients are often unable to perform exercise stress testing due to the underlying condition for which they require surgery. In this setting, pharmacological stress testing is invaluable in assessing the cardiac risk of patients prior to surgery.

Learn more about: Lexiscan

Learn more about: Lexiscan

Are there other tests for CAD that are noninvasive?

CT scanning

A new noninvasive test for the detection of CAD is electron beam computerized tomography (EBCT), or calcium scoring. Unlike the above mentioned stress tests that measure the heart's physiology, EBCT is designed to measure calcium deposits in the coronary arteries.

In patients with CAD, the plaques which make up the blockages contain significant amounts of calcium, which can be detected with the CT scanner and the amount of blockage is calculated by calcium scoring. This test will identify calcium in blockages as mild as 10%-20%, which would not be detected by standard physiological testing. When such mild blockages are detected, however, the only recommended therapy is risk factor modification (cholesterol lowering and cessation of smoking if applicable), and adjunctive use of aspirin and certain vitamins; such therapy would be advised in all patients with risk factors for CAD, regardless of the results of any noninvasive tests.

Learn more about: aspirin

Calcium scoring may be very helpful in convincing patients to change their lifestyle or take their medicines, as a score that is not zero implies that the blockage process is starting, and likely will progress unless lifestyle changes are made. It is important to realize that calcification is a function of age, and in younger patients (men under 50, women under 60) the calcium score is less helpful when low.

A more elaborate modality is CT angiography (ultrafast CT). This is a non-invasive (no catheter involved) form of angiogram, but still involves dye exposure and radiation, and is less precise than a coronary angiogram. This is still a rather new modality, and its role is still being defined.

What is the most accurate method of defining CAD?

The "gold standard" for the evaluation of CAD remains the coronary angiogram. Coronary angiography can be used to identify the exact location and severity of CAD; it is described below.

Coronary angiography

During a coronary angiogram (also termed a coronary catheterization), a small catheter (a thin hollow tube with a diameter of 2-3 mm) is inserted through the skin into an artery usually in either the groin or the arm. Guided with the assistance of a fluoroscope (a special X-ray viewing instrument), the catheter is then advanced to the opening of the coronary arteries, the blood vessels supplying blood to the heart. Next, a small amount of radiographic contrast (a solution containing iodine, which is easily visualized with X-ray images) is injected into each coronary artery. The images that are produced are called the angiogram.

Angiographic images accurately reveal the extent and severity of all coronary arterial blockages. Coronary angiography is performed with the use of local anesthesia and intravenous sedation, and is generally not terribly uncomfortable. The procedure takes approximately 20 to 30 minutes. After the procedure, the catheter is removed and the artery in the leg or arm is sutured, "sealed," or treated with manual compression to prevent bleeding. There is a small risk of serious complications from coronary angiography, as it is an "invasive" test, but in the hands of experienced physicians, this risk is quite small (well below one per cent). In appropriate patients, the therapeutic information learned from the angiogram is far more valuable than the relatively small risk of the procedure.

For patients with severe angina or heart attack (myocardial infarction), or those who have markedly abnormal noninvasive tests for CAD, the angiogram also helps the doctor select the optimal treatment, which may include medications, balloon angioplasty, coronary stent placement, or coronary bypass surgery. The coronary angiogram is the only test which allows the precise quantification of the extent and severity of CAD to optimally make these treatment decisions.

Picture of a coronary ballooon angiogram

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