Why is troponin so popular? How much do you know about the clinical application of myocardial injury markers?

Author: Gu Jin

Unit: Department of Clinical Laboratory, Hubei Provincial Hospital of Integrated Traditional Chinese and Western Medicine

The heart is the engine of the body's blood circulation, its rhythm of contraction and relaxation to ensure the adequate blood supply of various organs and tissues, when the heart has a disease, the cardiomyocytes that support it will degenerate and necrosis due to ischemia, inflammation, infection and other factors, resulting in heart muscle cell damage.

Myocardial injury markers are proteins and/or enzymes that are released into the peripheral blood when a cardiomyocyte is injured and detected. Detection of these substances can provide clinical diagnosis, disease monitoring, and risk stratification for acute myocardial infarction and other diseases with myocardial injury. However, the time, peak time, maintenance time and content of these substances released into the blood are different, and the change in their content in the blood can reflect to a certain extent whether the myocardium is damaged and the degree of damage, which is the origin of the myocardial injury marker.

This article will take stock of commonly used myocardial injury markers and their time windows.

1

Troponin (cTn): the gold standard of preference

Cardiac troponin is present on the fine muscle filaments of cardiomyocytes, and only 3% to 6% is present in the cytoplasm of myocytes. Calcarein is a complex of 3 subunits, namely troponin C, troponin I, and troponin T. Among them, serum myocardial troponin T and myocardial troponin I are specific markers of myocardial injury, and they appear early and can appear as early as 2 hours after the onset of symptoms.

Detection method: radioimmunoassay or chemiluminescence.

Reference value: cTnT0.2 μg/L is the diagnostic cut-off value, >0.5 μg/L can diagnose acute myocardial infarction, and cTnI1.5 μg/L is the diagnostic cut-off value.

Clinical significance: diagnosis of acute myocardial infarction: myocardial troponin is the preferred marker for the diagnosis of acute myocardial infarction. Myocardial troponin T begins to rise 3 to 6 hours after the onset of acute myocardial infarction, peaks in 10 to 24 hours, and returns to normal in 10 to 15 days; myocardial troponin I begins to rise 3 to 6 hours after the onset of acute myocardial infarction, peaks at 14 to 20 hours, and returns to normal in 5 to 7 days.

Myocardial troponin T and myocardial troponin I can sensitively reflect the presence of small focal, reversible myocardial injury.

It can be used for the judgment of reperfusion after thrombolysis.

2

Myoglobin (Mb)

Myoglobin is found in the heart muscle and skeletal muscle, and is extremely low in healthy human blood. Because myoglobin is relatively small in molecular weight and is present in the cytoplasm, it occurs earlier in muscle damage.

Detection methods: fluorescence immunoassay, chemiluminescence and electrochemiluminescence.

Reference: Male 28-72 μg/L; female 25-58 μg/L.

Clinical significance: diagnosis of acute myocardial infarction: myoglobin can be elevated 0.5 to 2 hours after the onset of acute myocardial infarction, peak at 6 to 12 hours, and return to normal in 18 to 30 hours.

3

serum creatine kinase (CK)

Creatine kinase is an important energy regulatory enzyme in the myocardium, under the energy provided by ATP, catalyzes the production of creatine phosphate creatine and ADP, creatine kinase is mainly distributed in skeletal muscle and myocardium, followed by cytoplasm and mitochondria of brain tissue.

Detection method: The CK total activity detection adopts the rate method.

Reference: Men 80-200U/L, Women 60-140U/L.

Clinical significance: diagnosis of acute myocardial infarction: creatine kinase is significantly elevated 3 to 8 hours after the onset of acute myocardial infarction, peaks in 10 to 36 hours, and returns to normal in 3 to 4 days. Acute myocardial infarction can be excluded if creatine kinase is less than the upper limit of the reference value, but small-scale myocardial injury and subendocardial infarction should also be excluded.

In viral myocarditis, creatine kinase is markedly elevated.

Creatine kinase can be elevated in polymyositis and skeletal muscle injuries caused by various causes, various intubation and postoperative procedures, intramuscular injection of chlorpromazine, etc.

4

Creatine kinase isoenzyme (CK-MB)

CK is a dimer consisting of two subunits, M and B, with three isoenzymes, CK-BB (distributed in the brain), CK-MB (distributed in the myocardium), and CK-MM (distributed in skeletal muscle).

Detection method: immunosuppressive method.

Reference value: CK-MB

Clinical significance: diagnosis of acute myocardial infarction: CK-MB increases 2 hours after the onset of acute myocardial infarction, peaks in 9 to 30 hours, and returns to normal in 2 to 3 days. The sensitivity and specificity of CK-MB for the diagnosis of acute myocardial infarction are superior to creatine kinase. The persistence of high levels of CK-MB after the onset of acute myocardial infarction indicates that myocardial infarction continues, and if it is descended and then elevated, it indicates that the site of the original infarction is expanding or a new infarction has emerged.

Angina, pericarditis, chronic atrial fibrillation, cardiac surgery, and coronary angiography also have elevated CK-MB.

Muscular dystrophy, polymyositis, amyotrophy, crush syndrome, intramuscular injection, etc., CK-MB can also be slightly elevated.

5

Serum lactate dehydrogenase and its isoenzymes

Lactate dehydrogenase (LD) is a key enzyme in glucose anaerobic fermentation that regulates the conversion of pyruvate to lactate, and is widely present in the cytoplasm and mitochondria of tissue cells such as liver, heart, skeletal muscle, lungs, spleen, brain, red blood cells, platelets, etc. LD is a tetramer with a molecular weight of 135 KD, consisting of five isoenzymes of M type and H type subunits: H4 (LD1), MH3 (LD2), M2H2 (LD3), M3H (LD4), M4 (LD5).

Detection method: Lactate dehydrogenase is commonly used to detect its total activity by rate method, while its isoenzyme is often determined by electrophoresis.

Reference value: lactate dehydrogenase: 200~380U/L when pyruvate is the substrate; 109~245U/L when lactic acid is the substrate. LD1 was 28.4% ±5.3%, LD2 was 41.0% ±5.0%, LD3 was 19.0% ±4.0%, LD46.6% ±3.5%, LD5 was 4.6% ±3.0%.

Clinical significance: When myocardial injury occurs, the membrane of cardiomyocytes ruptures, and mitochondria and intracytoplasmic substances leak out into the intercellular fluid and peripheral blood. Lactate dehydrogenase and its isoenzyme LD1 began to rise 8 to 12 hours after the onset of acute myocardial infarction, peaked in 48 to 72 hours, and returned to normal in 7 to 12 days. The continuous determination of lactate dehydrogenase has certain reference value for patients with acute myocardial infarction who are late in showing treatment and have returned to normal creatine kinase.

6

serum aspartic acid aminotransferase

Aspartate aminotransferase (AST), also known as glutamate aminotransferase (GOT), is widely distributed in various tissues of the human body. It is rich in liver, skeletal muscle, kidneys and heart muscle. Erythrocyte AST is about 10 times that of serum, and mild hemolysis elevates the assay results.

Detection method: continuous monitoring method.

Reference value:

Clinical significance: AST is elevated 6 to 12 hours after the onset of acute myocardial infarction, peaks at 24 to 48 hours, lasts for 5 days or 1 week, and then decreases. Because AST is not tissue-specific, elevated AST alone does not diagnose myocardial injury

7

Summary: Selection of markers of heart loss

1. Within 6h of symptom onset, it is advisable to detect cTn, Mb, CK-MB at the same time, the elevation time of these three markers generally does not exceed 6h, and the combined application helps to confirm the diagnosis and exclude the diagnosis early.

2. Symptoms occur for 2-3 days or more, it is advisable to detect LDH and cTn, these two markers can be maintained for up to one week, and cTn has myocardial specificity.

3.Mb early negative excludes AMI, late negative does not exclude; mid- to late-stage negative cTn does not completely exclude AMI because its maintenance time is limited.

4.cTn has replaced CK-MB as the preferred marker for detecting myocardial injury.

5. Serum myocardial markers are affected by a variety of factors, and the medical history must be clear when used to exclude possible effects on the existence of detection; symptoms, ecG and imaging performances are the basis for "textbook" diagnosis at different periods of heart damage; the accurate grasp and application of the time window of serum heart damage markers is helpful to clarify the diagnosis and evaluate the prognosis.

【Reference】

1. Wan Xuehong, Lu Xuefeng. Diagnostics, 8th ed. Beijing:People's Medical Publishing House,2013.]

2.Wang Hongli. Experimental Diagnostics. 2nd Edition. Beijing:People's Medical Publishing House,2010.]

3.JBS3 Board. Joint British Societies' consensus recommendations for the prevention of cardiovascular disease (JBS3). Heart. 2014 Apr;100 Suppl 2:ii1-ii67.

Editor: Ren Mileage Reviewer: Xiao Ran