Cardiac Biomarkers : Troponins,Creatinine Kinase Myoglobin...

Cardiac biomarkers refer to substances that are released into the bloodstream when the heart is damaged or under stress.

Serum cardiac biomarkers determinations play a vital role in the evaluation of patients who present with acute chest pain and in the diagnosis of acute coronary syndrome ie acute myocardial infarction.

These tests can also be used to help determine a person's risk of having these conditions or in monitoring and management of a patient with suspected ACS and cardiac ischemia.

Aminotransferases such as aspartate transaminase(AST), lactate dehydrogenase (LDH), and its subforms are longer used due to the fact that they lack cardiac specificity and their delayed elevation precludes the early diagnosis. You can check serum aminotransferases here;

serum aminotransferases

Creatinine Kinase

Creatine kinase (CK) is found in striated muscle and tissues of the brain, kidney, lung, and GI tract. It is a widely available marker but has low sensitivity and specificity for cardiac damage. In some noncardiac conditions such as trauma, seizures, hyperthyroidism, and renal insufficiency, CK levels may be elevated.

Currently, the CK marker largely has been replaced by cardiac troponins and CK-MB isoenzyme: CK-MB is cardiac-specific and is useful for the early diagnosis of acute myocardial infarction.

CK-MB typically is detectable in the serum 4–6 hours after the onset of ischemia, peaks in 12–24 hours, and normalizes in 2–3 days. Like the CK level, the peak CK-MB level does not predict infarct size; however, it can be used to detect early reinfarction or a second heart attack that occurs shortly after the first.

CK-MB may be used in follow up to an elevated CK and/or when the troponin test is not available.
Serial CK-MB levels commonly are obtained at admission to the emergency department and are repeated in 6–12 hours.

CK-MB subforms

CK-MB may be further characterized into subforms (or isoforms). CK-MB1 and CK-MB2.

CK-MB2 is found in myocardial tissue after myocardial infarction, and CK-MB1 is found in plasma (Tissue form). Normally, the tissue CK-MB1 isoform predominates; thus, the CK-MB2/CK-MB1 ratio is typically less than 1.

The CK-MB subform is not routinely used because of its laboratory labor-intensive nature.

CK-MB/CK relative index

The CK-MB/CK relative index that is calculated by the ratio of CK-MB to total CK is helpful in differentiating false-positive elevations of CK-MB which arise from skeletal muscle.

A ratio that is less than 3 is consistent with a skeletal muscle source, while the ratio that is greater than 5 is indicative of a cardiac source. Gray zone is the ratios between 3 and 5.

This index is useful if patients have only a myocardial infarction or only skeletal muscle injury, but not of any importance if the patient has both myocardial infarction and a skeletal muscle injury.

Acute myocardial infarction diagnosis should not be based on an elevated relative index alone, because sometimes the relative index may be elevated in clinical settings when either of the total creatinine kinase and CK-MB is within normal reference limits.

CK-MB/CK relative index is only useful when there is an elevation of both the total CK and the CK-MB levels.

Cardiac troponins

Troponins (T, I, C) are regulatory proteins found in striated and cardiac muscle.

There are 3 sub-units of troponin

Troponin I (TnI),
Troponin T (TnT), and
Troponin C (TnC).

Isoforms of troponin T and I differ, they are known as the “cardiac troponins.” They are the preferred cardiac biomarkers for the diagnosis of myocardial injury. Cardiac troponin is central to the definition of acute myocardial infarction (MI)

Troponin T and I generally have similar sensitivity and specificity for the detection of myocardial injury.
Unlike troponin I levels, troponin T levels may be elevated in patients with renal disease, polymyositis, or dermatomyositis.

These cardiac troponins typically are measured at emergency department admission and repeated in 6–12 hours.

Patients who have a normal CK-MB level but an elevated troponin level are considered to have sustained minor myocardial infarction, whereas the ones with elevated CK-MB and troponins are taken to have had a severe acute myocardial infarction.

The cardiac troponins may remain elevated up to two weeks after symptom onset, which makes them useful as late markers of recent acute myocardial infarction.

An elevated troponin T or I level is helpful in identifying patients at increased risk for death or the development of acute myocardial infarction.

The increased risk is related to the high serum troponin levels. The troponins also can help identify low-risk patients who may be sent home with close follow-up. Those with a normal or nearly normal ECG and a normal troponin I test 6 hours after admission had a very low risk of major cardiac events (0.3%) during the next 30 days.

Reference Ranges

Two different reference ranges are used in troponin assays.

The upper percentile reference limit gives the upper limit of what can be expected in a normal, healthy, adult population, while the coefficient of variation (CV) is the percent variation in assay results that can be expected when the same sample is repeatedly analyzed.

Myoglobin

Myoglobin is a small heme protein that stores oxygen in the skeletal and cardiac muscles. Its levels begin to rise as early as 2-4 hours after onset of infarction, peaks at 6-12 hours and returns to normal within 24-36 hours.

Normal myoglobin at 4 hours has a very high negative predictive value. However, myoglobulin lacks cardiospecificity.

Testing Strategy using cardiac biomarkers

In patients with definite or possible ACS, serial evaluation of cardiac markers is essential to diagnosing acute MI.

It is recommended that 3 different testing strategies are used to rule out non-ST elevation myocardial infarction (NSTEMI) in the emergency department.

One strategy is to use a single negative CK-MB, TnI, or TnT measured 8-12 hours after symptom onset.
Another strategy is to use negative myoglobin in conjunction with a negative CK-MB mass or negative TnI measured at baseline and at 90 minutes in patients presenting less than 8 hours after symptom onset.
A third approach is to use a negative 2-hour delta CK-MB in conjunction with a negative 2-hour delta TnI in patients presenting less than 8 hours after symptom onset.

Other cardiac biomarkers

B-type natriuretic peptide

B-type natriuretic peptide (BNP) is secreted primarily by the ventricular myocardium in response to wall stress, including volume expansion and pressure overload.

C-reactive protein

C-reactive protein (CRP), a nonspecific marker of inflammation, is considered to be directly involved in coronary plaque atherogenesis. Extensive studies show that an elevated CRP level independently predicted adverse cardiac events at the primary and secondary prevention levels.

Myeloperoxidase

Myeloperoxidase (MPO) is a leukocyte enzyme that generates reactant oxidant species and has been linked to prothrombotic oxidized lipid production, plaque instability and vasoconstriction from nitrous oxide depletion.

Some studies show significantly increased MPO levels in patients with angiographically documented coronary artery disease.

MPO may be a useful early marker in the ED based on its ability to detect plaque vulnerability that precedes ACS.