Significancy and clinical use of cardiac biomarkers
The substances which serum levels may be measured to estimate the condition of the heart muscle and therefore commonly used to diagnose the heart attack (myocardial infarction) and congestive heart failure are known as cardiac biomarkers.
So the cardiac biomarkers are used to:
- detect cardiac diseases;
- detect the risk of developing cardiac disorders;
- monitor the disorder;
- predict the response of a disorder to treatment.
Troponin complex includes 3 proteins or subunits – troponin C (TnC), troponin I (TnI), troponin T (TnT). Tests that estimate the level of troponin I and T are used for diagnostics of myocardial infarction.
The level of troponin in the serum <0.01 ng/mL is considered to be normal.
Troponin T increases 2 to 4 hours after the onset of myocardial necrosis, with a peak at about 24 hours, later the level of troponin decreases up to 14 days. When the level of troponin is lower than 0.2 ng/mL the test should be repeated at 3 and 6 hours to distinguish an acute and chronic elevation.
If the levels of troponin appear to be normal during 12 hours after the onset of chest pain the diagnosis of myocardial infarction is unlikely.
Creatine kinase MB fraction
CK is a dimeric molecule, composed of M and B subunits.
The 2 subunits can form 3 isozymes:
- CK-MM mainly found in the skeletal muscles;
- CK-MB found in the myocardium;
- CK-BB found in the neuronal tissue and the lungs.
The normal value for CK-MB is 3-5% of total CK, but peak CK-MB level can range from 15-30% of total CK in post-myocardial infarction, although a CK-MB fraction more than 6% of the total CK activity is regarded diagnostic for a heart attack.
CK – MB levels increase significantly 4–6 hours after myocardial infarction and peak at about 12-24 hours after the heart attack. If there is no further damage to the heart muscle, the CK-MB levels return to normal after 24 to 48 hours.
Myoglobin (MB) is an iron-containing cytoplasmic oxygen-binding protein, which is found in the cardiac muscle cells and skeletal/striated muscles.
The normal range of serum myoglobin is 0 to 85 ng/mL.
The level of myoglobin in the blood starts increasing within 2-3 hours after the heart attack and within 8-12 hours the level appears to reach its highest. Within one day the level returns back to normal.
The test is nonspecific for myocardial infarction. However, the level of myoglobin increases sooner than creatine kinase MB fraction after the heart attack. If the myoglobin level does not increase within 12 hours after the chest pain occurred, an infarction is very unlikely.
C-reactive protein (CRP) is produced by the liver. The protein may also be synthesized by cells in the vascular wall by the endothelium (the lining of the vessels), smooth muscle cells. The level of CRP increases when there is inflammation somewhere in the body. It was established that in atherosclerosis the concentration of the CRP rises, although it doesn’t reach the values seen in patients with infection/inflammation. Therefore thigh-sensitivity CPR test may be used as a cardiac biomarker.
The reference range for C-reactive protein is:
- High-sensitivity CRP (hs-CRP): < 3 mg/L;
Lactate dehydrogenase (LD) is a protein that catalyzes the oxidation of lactate to pyruvate. There are 5 different types of LD. LD-1 (H4) and LD-2 (H3M) are found in the heart muscle and their increased concentrations may be detected in myocardial infarction. LD-1 is elevated in the serum about 24 to 48 hours after the heart attack. The so-called flip in the LD-1/LD-2 from less than 1 to greater than 1 is seen after a severe heart attack.
Brain natriuretic peptide
Brain natriuretic peptide (BNP) is a hormone and N-terminal-pro-BNP (NT-pro-BNP) in a non-active prohormone, which is synthesized by the heart. The measurement of their level in the serum is used to detect, evaluate the heart failure and the response to treatment as the pressure within the heart chambers and the stretch of the heart muscle affect the production of the BNP and NT-pro-BNP. NT-pro-BNP concentration correlates with heart failure severity.
A normal level of the BNP reference range is:
- < 100 pg/mL for patients aged 0-74 years
- somewhat above 100 pg/mL, but under 400 pg/mL for patients aged 75-99 years
A normal level of NT-proBNP reference range is:
- < 125 pg/mL for patients aged 0-74 years
- < 450 pg/mL for patients aged 75-99 years