Coronary Heart Disease: Diagnosis

Diagnosis of atherosclerosis and CHD is based on knowledge of a patient’s individual risk factors, along with a careful medical history, physical exam, and diagnostic tests.

Blood Tests

No blood test can definitively diagnose atherosclerosis. However, epidemiological studies have found fibrinogen,¹ white blood cell counts,² cholesterol, C–reactive protein, and homocysteine concentrations associated with plaque formation and heart disease risk. For MI, a number of laboratory tests are available, but none is completely sensitive or specific. Correlation with patient symptoms, electrocardiograms, and angiographic studies is crucial.

Creatine kinase–MB fraction (CK–MB). CK–MB is a specific marker for acute myocardial injury. The serum concentration rises within 2 to 8 hours of the onset of acute MI. Serial measurements every 2 to 4 hours (for about 12 hours) help determine the extent and time frame of myocardial injury. CK–MB is also useful for the determination of reinfarction, or extension of myocardial injury. Concentrations normally decrease after 1 to 3 days, so subsequent elevations or plateaus indicate another myocardial infarction.

Troponins. These are proteins that combine with calcium to facilitate cardiac muscle cell contraction through actin–myosin interaction. Troponins are released into the bloodstream during myocardial injury. Troponin T lacks specificity for myocardial injury, because it is also present in skeletal muscle cells. Troponin I is more specific for myocardial injury than troponin T or CK–MB.

Levels of both tropinin I and CK–MB increase during the early course of a myocardial infarction. Because troponin I remains elevated for 5 to 14 days, it has greater sensitivity than CK–MB and LDH as a marker for diagnosing recent MI. However, this prolonged elevation may mask reinfarction or extension of infarction in the early days after an initial event.

Cholesterol. Elevated total and low–density lipoprotein (LDL) cholesterol concentrations, and low high–density lipoprotein (HDL) cholesterol concentrations (less than 50 mg/dL in women and 40 mg/dL in men), increase the risks for atherosclerosis and CHD events. Although the National Cholesterol Education Program defines elevated total cholesterol concentration as above 200 mg/dl and elevated LDL cholesterol concentration as above 100 mg/dL (with higher thresholds for some groups), evidence indicates a significant benefit for maintaining lower levels.³ In epidemiologic studies and clinical trials, CHD event risk continually decreases until total cholesterol is below about 150 mg/dL. Many experts now call for LDL cholesterol concentrations below 70 mg/dL for high–risk patients or for secondary prevention, and CHD risk continuously decreases until LDL is below 40 mg/dL.⁴

Triglycerides. Elevated concentrations (above 150 mg/dL) increase risk for heart disease.

Homocysteine. Elevated levels (above 12 µmol/L) may cause damage to arterial walls, thus increasing the risk for plaque formation. Men normally have a slightly higher homocysteine concentration than women. Levels tend to increase with age. Although homocysteine levels have been correlated with CHD risk, neither a cause–effect relationship nor a treatment outcomes benefit has been established in clinical trials.⁵

C–reactive protein (CRP). CRP is an acute phase marker of inflammation, nonspecific for etiology and location other than in clinical context. High sensitivity–CRP (hs–CRP) has been found to be associated with increased risk of cardiac events, with levels greater than 3 mg/dL associated with greatest risk.⁶ However, hs–CRP has not reliably been shown to have a cause–effect relationship or a treatment outcome benefit in cardiovascular disease. The usefulness of CRP and many other inflammatory and acute phase reactants as screening measures or therapeutic targets in cardiovascular disease remains unproven,^7–10 pending the results of additional clinical trials. The NIH–funded Atherosclerosis Risk in Communities Study (ARIC) concluded that routine measurement of CRP, homocysteine and 17 other novel risk markers is not warranted, and reinforced the utility of standard risk factor assessment and management.¹¹

Noninvasive Tests

EKG. Findings may include ST elevation (acute myocardial injury or infarction) or depression (myocardial ischemia), T wave inversion (myocardial ischemia or MI), and ventricular premature complexes.

Stress tests. Methods include treadmill or bicycle exercise stress tests (EST), and EST or pharmacologic stress tests combined with nuclear imaging or echocardiography. These tests may be used for CHD diagnosis, risk stratification, and prognosis, and often help determine the advisability for cardiac catheterization and revascularization.

EKG changes and symptoms (eg, exertional chest pain) are monitored during stress tests, providing both determinants of CHD presence and severity, and indications for test termination. Pharmacologic stress modalities are typically used when an exercise stress test is inappropriate or inconclusive. Pharmacologic stress agents include coronary vasodilators, such as dipyridamole and adenosine, and cardiac inotropes, such as dobutamine and (less commonly) arbutamine.

Other Imaging Tests

Cardiac catheterization with coronary angiography. A catheter is inserted into a peripheral artery (usually a femoral artery) and advanced under fluoroscopic guidance to the coronary artery ostia. A radiopaque dye is then injected to identify the locations and severities of coronary blockages. This invasive procedure is performed when coronary artery stenosis is known or suspected, and the need for coronary artery angioplasty, stent placement, or bypass surgery is anticipated. 

Intravascular ultrasound (IVUS). IVUS is highly sensitive to the presence and composition of coronary artery plaques. Its 2 major uses currently are to clarify the severity of stenoses identified on angiography, and to assess the deployment of coronary artery stents.

Computed tomography (CT). Electron beam tomography (EBT) accurately identifies and quantifies coronary artery calcification. This test has several applications in CHD, including diagnosis, disease distribution, risk stratification, prognosis, and treatment decisions. EBT is a helpful screening method in specific patient populations, but has limited value for low–risk, asymptomatic patients.
CT angiography (CTA) uses intravenous contrast to obtain noninvasive coronary angiograms. Technical advances such as 64–slice scanners can produce angiograms that rival invasive coronary angiography, and the entire approach to CHD diagnosis and risk stratification may change as this technology continues to improve.

Magnetic resonance imaging (MRI). Cardiac MRI has historically been best suited for evaluation of cardiac chambers, pericardium, thoracic vessels, and congenital heart disease. However, technical advances to minimize the effects of cardiac motion have expanded MRI applications to include CHD evaluation. Such applications overlap substantially with CTA, and the role for MRI in CHD remains uncertain.