Cardiac marker tests
Cardiac marker tests identify blood chemicals associated with myocardial infarction (MI), commonly known as a heart attack. The myocardium is the middle layer of the heart wall composed of heart muscle. Infarction is tissue death caused by an interruption in the blood supply to an area.
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.
C-reactive protein results may be affected by the use of oral contraceptives, NSAIDs, steroids, salicylates, and intrauterine devices (IUDs). Homocysteine levels may be affected by smoking, diabetes, and coffee.
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, CKMB, 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 10–24 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. CK-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 forms 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 forms are different molecular forms of MB found in the circulation. When MB is released into the blood, part of the M subunit is removed by an enzyme in the plasma. This results in a molecule called CK-2 1 . This is the prevalent form of MB in the blood. CK-2 2 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 form.
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.
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. Cardiac troponins are specific to heart muscle. They have enabled the development of assays (tests) 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 a 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 (measures amounts) immunoassays are available for the measurement of cTnI and cTnT. There is also a qualitative (positive or negative) cTnI test, targeted at bedside testing.
C-reactive protein (CRP)
CRP is a protein found in serum or plasma at elevated levels during a inflammatory processes. The protein can be measured via a variety of methods for the quantitative or semiquantitative determination of C-reactive protein in human serum.
CRP binds to part 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 (such as a blood clot causing MI). 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 (0.1–2.5 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 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 a lack of certain B vitamins, inheritance, or dietary excess and have been implicated in vascular-wall injury. 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.
These assays require a sample of blood, which is typically obtained via a standard vein puncture procedure. Homocysteine tests require the patient to fast.
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.
There are no complications associated with these tests.
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.
- Total CK: Reference value is 38–174 units/L for men and 96–140 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 10–13 units/L. The values begin to rise within three to four hours and peak at 10–24 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 10–24 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 10–24 hours. Values return to normal within five to 10 days.
- CK-MB forms: 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 12–24 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 12–24 hours.
- Homocysteine: The normal fasting level for plasma is 5–15 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 20–500 mg/dL.
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Victoria E. DeMoranville Mark A. Best