Introduction
Acute coronary syndrome (ACS) is the predominant cause of morbidity and mortality worldwide. Biomarkers help in providing evidence about a myocardial injury. This helps detect injury and possible heart complications beforehand. Therefore, myocardial biomarkers play an essential role in preventing inevitable heart conditions.
What Is the Importance of Troponin?
Troponin is the gold standard biomarker for myocardial injury. It is commonly used along with creatine kinase-myoglobin binding (CK-MB) and myoglobin to enable a more precise diagnosis of ACS. The important biomarkers apart from troponin that point towards ACS are B-type natriuretic peptides, ischemia-modified albumin, copeptin, heart-type fatty acid binding protein, myeloperoxidase, C-reactive protein, placental growth factor, choline, and growth differentiation factor-15. These have been shown to improve the diagnosis and prognosis of myocardial injury compared to the traditional biomarkers.
What Are the Important Biomarkers of Myocardial Injury Other Than Troponin?
The important biomarkers other than troponin are:
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CK-MB: CK-MB is one of the three major creatine kinase isoenzymes. It is predominantly found in the brain, skeletal muscle, and myocardium. CK-MB is released in ischemia and rapidly during myocardial necrosis (death of cells). For years, serial measurements of CK-MB were the gold standard in diagnosing myocardial infarction. When measured during mass assays, CK-MB has the specificity and sensitivity to evaluate ACS patients.
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Myoglobin: Myoglobin is a tiny cytoplasmic heme protein that is found in all muscles of the body. In cases of myocardial necrosis, the levels rise swiftly within one to three hours, peak by six to nine hours, and become normal in less than 24 hours. Among the conventional biomarkers, myoglobin rises within less than two hours of the onset of chest pain. This is because of its relatively small size and high cytoplasmic content.
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B-Type Natriuretic Peptide (BNP): A B-type natriuretic peptide is a hormone produced by the heart. The BNP molecule also releases a prohormone called N Terminal prohormone BNP (NT-proBNP). Both BNP and NT-proBNP are released into the blood when there are changes in heart pressure. These changes can occur due to heart failure or other cardiac conditions. The levels of these hormones rise when heart failure occurs or gets worse, whereas the levels decrease when heart failure stabilizes. In most cases, BNP and NT-proBNP are higher in patients with cardiac failure compared to normal people.
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Copeptin: Copeptin is a glycosylated peptide. It is a stable compound in serum and easy to measure. Normal copeptin secretion helps maintain plasma osmolality (a factor that measures the body's electrolyte and water balance). In severe diseases like shock, stroke, sepsis, or cardiovascular diseases, there is a sharp increase in plasma copeptin levels. Therefore, it is considered an essential biomarker in diagnosing myocardial injury. In addition, it also carries a piece of important prognostic information.
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Ischemia-Modified Albumin (IMA): Ischemia is the diminished blood supply to a tissue or organ that leads to a shortage of oxygen supply to that part. IMA has been approved by the US FDA (United States Food and Drug Administration) as a biomarker for acute ischemia. IMA is the "N-terminal modified albumin."
During ischemia, the N-terminus of albumin gets destroyed. This disables it from binding to metals and becomes incapable of being measured by an albumin-cobalt binding test. However, IMA can detect acute ischemia before necrosis as its blood levels increase within minutes of ischemia onset and return to normal within 6 to 12 hours. Therefore, ischemia-modified albumin has been implicated in diagnosing acute ischemia that occurs before necrosis.
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Heart-Type Fatty Acid Binding Protein: Heart-type fatty acid binding protein (H-FACP) is a low molecular weight protein in the cell membrane of myocytes. It is involved in the transport and metabolism of fatty acids from the blood into the heart cells. Though it is present majorly in the heart tissue, a small part is also present in the brain, skeletal muscle, and kidneys. Owing to its small size, it easily leaks out of the myocardial cells when there is an injury and ischemia. Therefore, several studies have approved it as a biomarker for myocardial injury.
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Myeloperoxidase (MPO): Myeloperoxidase is released by activated neutrophils. It has powerful proinflammatory and pro-oxidative properties. It is an inflammatory enzyme found in large quantities in ruptured atherosclerotic plaques (atherosclerotic plaques are a build-up of cholesterol, fat, calcium, and inflammatory cells that build up in the walls of arteries). Levels of MPO correlate with other markers of inflammation like interleukin-6, C-reactive protein, tumor necrosis factor-alpha, and white blood cell count. MPO is released during acute inflammation by macrophages and neutrophils. Recently, myeloperoxidase has been considered a useful risk marker for diagnosing acute coronary syndrome and patients admitted to the emergency room for the complaint of chest pain.
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CRP (C-Reactive Protein): CRP is an acute-phase protein formed in the liver. The levels rise when there is inflammation. CRP activates the complement system, and by doing so, it binds to the damaged cells, which include those of the infected myocardium. Recently, the goal has been to determine CRP's diagnostic and prognostic effects. However, the results are conflicting if CRP is a nonspecific marker of inflammation.
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Choline: Phospholipids make up the cell membrane. Choline is a water-soluble essential nutrient found in phospholipids. Choline gets released into the blood upon the breakdown or cleavage of phospholipids. Choline is considered a potential biomarker for the diagnosis and prognosis of ischemia, necrosis, and ACS. A recent study conducted on patients admitted to the hospital revealed that choline is a vital predictor of cardiac arrest and death. It was also found helpful in identifying patients with high-risk unstable angina.
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Placental Growth Factor (PIGF): Like CRP, PIGF is a marker of vascular inflammation. It stimulates the angiogenesis and proliferation of inflammatory cells. This, in turn, produces collagen-degrading enzymes that bind to the vascular walls. Therefore, PIGF plays a role in plaque vulnerability and rupture that result in cardiovascular events. PIGF is also essential in the risk stratification of patients with ST-Elevation Myocardial Infarction (STEMI).
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Soluble CD 40 Ligand (sCD40L): CD40 Ligand is a member of the tumor necrosis factor superfamily. It is produced by activated platelets and lymphocytes, which indicate the activation of inflammatory processes. The soluble form of CD40 Ligand (sCD40L) is a mediator of inflammation and hemostasis. Therefore, it is implicated in diagnosing atherosclerosis.
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Growth-Differentiation Factor-15 (GDF-15): GDF-15 is a cytokine that regulates multiple systems. An increase in GDF-15 has been observed in myocardial injury. It is believed that GDF-15 plays an essential role in the diagnosis and prognosis of ACS as serum GDF-15 values are found to elevate after an ischemic event.
Conclusion
The future of biomarkers in detecting myocardial injury may pave the way for a multimarker approach. Some studies already support this idea. For example, a study using troponin, CRP, and NT-proBNP suggested worse outcomes when two to three biomarkers were used to assess the condition compared to one. Also, early biomarkers for inflammation may identify high-risk patients and plan for more aggressive intervention.
