Cardiac Marker Tests

Definition

Cardiac marker tests identify blood analytes associated with myocardial infarction (MI), commonly known as a heart attack.

Purpose

Cardiac markers help physicians to assess acute coronary syndromes and to identify and manage high-risk patients. Creatine kinase-MB (CK-MB), myoglobin, homocysteine, C-reactive protein (CRP), troponin T (cTnT), and troponin I (cTnI) are all used for assessment of the suspected acute myocardial infarction. CK-MB, cTnT, and cTnI may also be used to identify and manage high-risk patients.

Precautions

C-reactive protein results may be affected by the use of oral contraceptives, NSAIDs, steroids, salicylates, intrauterine devices (IUDs), and overnight sample refrigeration. Homocysteine levels may be affected by smoking, diabetes, and coffee.

Description

Creatine kinase (CK)

Creatine kinase is an enzyme responsible for transferring a phosphate group from ATP to creatine. It is composed of M and/or B subunits that form CK-MM, CK-MB, and CK-BB isoenzymes. Total CK (the activity of the MM, MB, and BB isoenzymes) is not myocardial-specific. However, the MB isoenzyme (also called CK-2) comprises about 40% of the CK activity in cardiac muscle and 2% or less of the activity in most muscle groups and other tissues. In the proper clinical setting, MB is both a sensitive and specific marker for myocardial infarction. MB usually becomes abnormal three to four hours after an MI, peaks in 10 to 24 hours, and returns to normal within 72 hours. However, an elevated serum MB may occur in people with severe skeletal muscle damage (such as in muscular dystrophy or a crush injury) and renal failure. In such cases, the CK index (MB divided by total CK) is very helpful. If the index is under 4%, a nonmyocardial cause of a high MB should be suspected. C-MB is considered the benchmark for cardiac markers of myocardial injury. Measurement of CK-MB may be performed via electrophoresis or immunoassays; the latter demonstrates better analytical sensitivity and better precision.

CK-MB isoforms can be used to determine whether thrombolytic therapy (such as treatment with tissue plasminogen activator to dissolve a blood clot in the coronary artery) has succeeded. MB isoforms are different molecular forms of MB found in the circulation. When MB is released into the blood, the terminal lysine of the M subunit is removed by an enzyme in the plasma. This results in a molecule with faster electrophoretic mobility, called CK-2₁. This is the prevalent form of MB in the blood. The slower form, designated CK-2₂, is the unmodified cardiac form of MB. After successful thrombolytic therapy, the unmodified form of MB is rapidly flushed into the blood, causing it to become the dominant isoform.

Myoglobin

Myoglobin is a protein found in both skeletal and myocardial muscle. It is released rapidly after tissue injury and may be elevated as early as one hour after myocardial injury, though it may also be elevated due to skeletal muscle trauma. However, if myoglobin values do not rise within three to four hours after a person shows acute symptoms, it is highly unlikely that he or she had an MI. There are several measurement methods available, including fluorometric, nephelometric, and turbidmetric assays; plus immunochromatography-based tests designed for qualitative, point-of-care testing.

Troponin T and troponin I

Troponin C, I, and T are proteins that form the thin filaments of muscle fibers and regulate the movement of contractile proteins in muscle tissue. Skeletal and cardiac forms are structurally distinct, and antibodies can be produced that react only with the cardiac forms of troponin I and troponin T.

Cardiac troponin T (cTnT) and cardiac troponin I (cTnI) are the newest additions to the list of cardiac markers. Troponins are specific to heart muscle. They have enabled the development of assays that can detect heart muscle injury with great sensitivity and specificity. While these markers have been used mainly to aid in the diagnosis of chest-pain patients with nondiagnostic electrocardiograms, they are also used as prognostic indicators of an MI. According to the American Heart Association, "Several studies have identified a measurable relationship between cardiac troponin levels and long-term outcome after an episode of chest discomfort. They suggest that these tests may be particularly useful to evaluate levels of risk. In other words, it's possible that the results of a troponin test could be used to identify people at either low risk or high risk for later, serious heart problems."

Several commercially available quantitative immunoassays are available for for the measurement of cTnI and cTnT. There is also a qualitative cTnI test, targeted at bedside testing.

C-reactive protein (CRP)

CRP is a protein found in serum or plasma at elevated levels during inflammatory processes. The protein can be measured via a variety of methods, including EIA or ELISA, for the quantitative or semiquantitative determination of C-reactive protein in human serum, particle agglutination tests that provide semiquantitative results, and laser and rate nephelometry tests that measure antigen-antibody complexes by light dispersion.

CRP binds to the C polysaccharide of the capsule of Streptococcus pneumoniae. It is a sensitive marker of acute and chronic inflammation and infection, and in such cases is increased several hundred-fold. Several recent studies have demonstrated that CRP levels are useful in predicting the risk for a thrombotic event. These studies suggest that a high-sensitivity assay for CRP be used that is capable of measuring the very low level normally found in serum (0.1 to 2.5 mg/L). Heart patients who have persistent CRP levels between 4 and 10 mg/L, with clinical evidence of low-grade inflammation, should be considered to be at increased risk for thrombosis. People can be stratified into four groups of increased risk based upon the quartile in which their CRP levels fall.

Homocysteine

Homocysteine is an amino acid. According to the American Heart Association, studies have shown that too much homocysteine in the blood is related to a higher risk of coronary heart disease, stroke, and peripheral vascular disease; and that it may also have an effect on atherosclerosis. High levels of homocysteine are the result of inheritance or dietary excess and have been implicated in vascular-wall injury. One immunoassay is available for it. It is believed that laboratory testing for plasma homocysteine levels can improve the assessment of risk, particularly in patients with a personal or family history of cardiovascular disease, but in whom the well-established risk factors (smoking, high blood cholesterol, high blood pressure, physical inactivity, obesity, and diabetes) do not exist. Homocysteine levels are obtained via high-performance chromatography with electrochemical detection.

Preparation

These assays require a sample of blood, which is typically obtained via a standard venipuncture procedure. Homocysteine tests require the patient to fast. Homocysteine is stable only in separated refrigerated or frozen plasma for 48 hours.

Aftercare

Discomfort or bruising may occur at the puncture site, or the person may feel dizzy or faint. Applying pressure to the puncture site until the bleeding stops reduces bruising. Warm packs to the puncture site relieve discomfort.

Complications

There are no complications associated with these tests.

Results

Normal results vary, based on the laboratory and method used. Unless otherwise specified, the following information is from the American College of Cardiology and the American Heart Association.

KEY TERMS

Cardiac marker— A substance in the blood that rises following a myocardial infarction.

Diagnostic window— A cardiac marker's timeline for rising, peaking, and returning to normal after a heart attack.

Myocardial infarction (MI)— Commonly known as a heart attack, a myocardial infarction is an episode in which some of the heart's blood supply is severely cut off or restricted, causing the heart muscle to suffer and die from lack of oxygen.

Myoglobin— A protein that holds oxygen in heart and skeletal muscle. It rises after damage to either of these muscle types.

• Total CK: Reference value is 38 to 174 units/L for men and 96 to 140 units/L for women. The values begin to rise within four to six hours and peak at 24 hours. Values return to normal within three to four days.
• CK-MB: Reference value is 10 to 13 units/L. The values begin to rise within three to four hours and peak at 10 to 24 hours. Values return to normal within two to four days.
• Troponin T: Reference value is less than 0.1 ng/mL. The values begin to rise within two to four hours and peak at 10 to 24 hours. Values return to normal within five to 14 days.
• Troponin I: Reference value is less than 1.5 ng/mL. The values begin to rise within two to four hours and peak at 10 to 24 hours. Values return to normal within five to 10 days.
• CK-MB isoforms: Reference value is a ratio of 1.5 or greater. The values begin to rise within two to four hours and peak at six to 12 hours. Values return to normal within 12 to 24 hours.
• Myoglobin: Reference value is less than 110 ng/mL. The values begin to rise within one to two hours and peak at four to eight hours. Values return to normal within 12 to 24 hours.
• Homocysteine: The normal fasting level for plasma is five to 15 micromol/L. Moderate, intermediate, and severe hyperhomocysteinemia refer to concentrations between 16 and 30, between 31 and 100, and less than 100 micromol/L, respectively.

• C-reactive protein: According to the U.S. Food and Drug Administration, in healthy people, reference values are below 5 mg/dL; in various diseases, this threshold is often exceeded within four to eight hours after an acute inflammatory event, with CRP values reaching approximately 20 to 500 mg/dL.

Health care team roles

Cardiac marker tests are usually performed by clinical laboratory scientists, medical technologists, or clinical laboratory technicians.

Resources

BOOKS

Wu, A., editor. Cardiac Markers. Washington, DC: American Association of Clinical Chemistry (AACC) Press, 1998.

PERIODICALS

Brown, C. S., and B. D. Bertolet. "Cardiac Troponin. See Ya Later, CK!" Chest (January 1997): 2-4.

Chesebro, M. J. "Using Serum Markers in the Early Diagnosis of Myocardial Infarction." American Family Physician (June 1997): 2667-2674.

Christenson, R. H., et al. "Cardiac Markers in the Assessment of Acute Coronary Syndromes." Proceedings from the First Maryland Chest Pain Center Research Conference (date not available).

Hamm, C. W., et al. "Emergency Room Triage of Patients with Acute Chest Pain by Means of Rapid Testing for Cardiac Troponin T or Troponin I." The New England Journal of Medicine (December 4, 1997): 67-78.

"In Vitro Diagnostic C-Reactive Protein Immunological Test System." U.S. Food and Drug Administration: Center for Devices and Radiological Health. (July 20, 1998).

Keffer, J. "Myocardial Markers of Injury. Evolution and Insights." American Journal of Clinical Pathology (March 1996): 305-320.

Mercer, D. W. "Role of Cardiac Markers in Evaluation of Suspected Heart Attack. Selecting the Most Clinically Useful Indicators." Postgraduate Medicine (November 1997): 113-117, 121-122.

Wong, S. S. "Strategic Utilization of Cardiac Markers for the Diagnosis of Acute Myocardial Infarction." Annals of Clinical and Laboratory Science (July 1996): 301-312.

OTHER

"ACC/AHA Guidelines for the Management of Patients with Acute Myocardial Infarction," American College of Cardiology and the American Heart Association, 1999.

American Heart Association. 〈http://www.americanheart.org/Heart_and_Stroke_A_Z_Guide/bloodt.html〉.

ARUP Laboratories. 〈http://www.arup-lab.com〉.