Cardiac Markers and their Pattern of Release

A cardiac marker is a clinical laboratory test that is useful in the detection of acute myocardial infarction or minor myocardial injury.

Many tests have been used to assess cardiac injury.

The most commonly available tests includes:

• CK isoenzymes
• Lactate dehydrogenase enzyme (LDH)
• Myoglobin
• Cardiac troponin

Cardiac Enzymes (cardiac biomarkers):

Creatinine Kinase Isoenzymes and Isoforms:

Both cytosolic and mitochondrial isoenzymes have been identified.

The cytosolic form of the enzyme is a dimer composed of two subunits (M and B) and thus has three isoenzymes – CK-3 (MM), CK-2 (MB), CK-1 (BB).

CK –MB is more specific for the myocardium.

Normal skeletal muscle contains approximately 1 % CK–MB enzyme of total CK enzyme.

Severe skeletal muscle injury after trauma of surgery can lead to absolute elevations of CK – MB above the upper reference limit in serum, with percent CK – MB is serum less 1 % of the total CK enzyme.

Increase in total CK and CK -2 in several patient groups often present a diagnostic challenge to the clinician.

For example, persistent elevations of serum CK –MB resulting from chronic muscle disease occur in individuals with muscular dystrophy and polymyositis, as well in healthy subjects who undergo extreme exercise of physical activities.

Cytosolic Enzyme:

1.     CK1 (BB) predominant and more specific for the brain

2.     CK-2 (MB) predominant and more specific for the myocardium.

3.     CK-3 (MM) predominant in both the heart and skeletal muscle

Mitochondrial Enzyme:

Two isoenzymes

1.     CK

2.     CK-MT

Cardiac Proteins (cardiac biomarkers):

1.      Myoglobin

Myoglobin is a low – molecular weight oxygen – binding protein and located in cytoplasm, this is the reason for its early appearance in circulation after muscle injury.

Increase in serum myoglobin occur after trauma to either skeletal or cardiac muscle, as in crush injuries or acute myocardial infraction (AMI).

Serum myoglobin methods are unable to distinguish the tissue of origin. Even minor injury to skeletal muscles may result in an elevated concentration of serum myoglobin, which may lead to the misdiagnosis of AMI.

Myogobin utility

• A major advance offered by myoglobin as a serum marker for myocardial injury, is that it is released early from the damaged cells
• Concentration rises 1 hour after the onset of symptoms
• Peak activity in 4 to 12 hours (sensitivity 90 to 100 %). This peak suggests that serum myoglobin reflects the early course of myocardial necrosis.
• The best use of early serum myoglobin measurement after admission to the emergency department is a negative predictor of AMI.

2.      Cardiac Troponin

Cardiac troponin I and T: These contractile proteins of all myofibrils include the regulatory protein troponin.

Troponin is a complex of three protein sub-units

1. Troponin T
2. Troponin I
3. Troponin C

Location: Troponin is localized primarily in the myofibrils with a smaller cytoplasmic fraction.

On injury, troponin is released into circulation.

Cardiac troponin utility

The early-release of both cardiac troponin I (cTnl) and cardiac troponin T (cTnT) are similar to those of CK-MB after an AMI.

Increases above the upper reference limit are seen at 4 to 8 hours.

cTnl and cTnT also can remain elevated for up to 5-10 days respectively, after an AMI occurs.

The mechanism is likely the ongoing release of troponin from the approximately 95% myofibril-bound fraction.

The long time interval of cardiac troponin increase means it can replace the LD isoenzymes assay in the detection of late presenting AMI individuals.

Clinical evidence is mounting that either cTnl or cTnT should replace CK-MB as the test of choice to rule in or rule out an AMI.

The following order patterns are recommended: Myoglobin (early marker) and either cTnT (definitive mid to late marker) at presentation and at 3 to 6 hour, and 12 to 24 hours after presentation. If the tests are not done within 9 hours of presentation, then a myoglobin measurement is not recommended as a cost-effective measure.

Troponin T: The clinical sensitivity of cTnT is better than CK-MB for diagnosis of MI after the onset of chest pain.

Troponin I: cTnl is specific for myocardium. It will not be elevated unless a myocardial injury is present.

Use of either cTnT or cTnl appears to offer better assessment of risk compared to using CK-MB.

Timing of cardiac markers in MI

Markers	Time (hours) until marker increases above upper reference limit	Time (hours) until peak conc.	Time (days) until return to with in reference  interval
CK	3 to 8	10 to 24	3 to 4
CK-2	3 to 8	10 to 24	2 to 3
LD, LD-1	8 to 12	72 to 144	8 to 14
MYOGLOBIN	1 to 3	6 to 9	1
TROPONINS I AND T	3 to 8	24 to 48 (first peak) 72 to 100 (second peak: T only)	3 to 5 (I) 5 to 19 (T)