Cardiac Markers

Lipoprotein-associated phospholipase 2 (Lp-PLA2), also known as platelet-activating factor acetylhydrolase (PAF-AH), is composed of 441 amino acids encoded by the PLA2G7 gene, with a molecular weight of about 45 kDa. Lp-PLA2 is synthesized and secreted by mature macrophages and lymphocytes and is regulated by inflammatory mediators. It has a pro-inflammatory and pro-atherosclerotic effect. In recent years, more and more evidence has shown that it plays a role in promoting atherosclerosis (AS) and is a new inflammatory marker of AS. The concentration of Lp-PLA2 in the blood can dynamically reflect the degree of inflammation of atherosclerotic plaques, and the higher the concentration, the greater the risk. In addition, detecting the level of Lp-PLA2 in the blood can be used to identify high-risk individuals with coronary heart disease. According to research by Mayo Medical Laboratories, when the concentration of Lp-PLA2 in the blood is higher than 235 ng/mL, it indicates an increased risk of cardiovascular diseases such as myocardial infarction, coronary heart disease and ischemic stroke. Lp-PLA2 is an independent risk factor for reflecting the risk of rupture of atherosclerotic plaques and thrombosis events. It has high consistency and accuracy with it and is an accurate risk assessment marker for high-risk patients with acute atherosclerotic thrombotic recurrence events.

Growth Differentiation Factor-15 (GDF-15) is one of the TGF-β superfamily members. In the synthesis process, the precursor protein is formed first. After the protein is cleaved and released by N-terminal peptides, it becomes the mature form of GDF-15 and is secreted into the serum in the form of a 25kD dimer. Because it was first discovered in activated macrophages and its expression level is high in normal placenta, it is also called Macrophage Inhibitory Cytokine-1 (MIC-1) and Placental Transforming Growth Factor-β (PTGF-β). In healthy people, the expression level of GDF-15 in tissues other than the placenta is extremely low; under pathological conditions such as inflammation, tumors, and cardiovascular diseases, the expression level of GDF-15 is significantly increased. Under normal physiological conditions, GDF-15 is almost not expressed in the heart. When cardiovascular damage occurs, such as pressure overload, heart failure, ischemia/reperfusion injury and atherosclerosis, the serum GDF-15 level increases significantly.

Myeloperoxidase (MPO) is a hemoprotein that is rich in neutrophils. It is synthesized and stored in azurophilic granules in the bone marrow before entering the circulation. External stimuli can cause neutrophils to aggregate, thereby releasing MPO. The relative molecular weight of MPO is 150kDa. It is a tetramer formed by the covalent combination of two subunits. Each subunit has a heavy chain α (relative molecular weight 60kDa) and a light chain β chain (relative molecular weight 15kDa). MPO can kill microorganisms by catalyzing the production of hypochlorous acid through oxidation of chloride ions in phagocytes, destroying various target substances, and playing a role in producing and regulating inflammatory responses. More importantly, its oxidative modification of low-density lipoprotein (LDL) can cause atherosclerosis. Therefore, MPO is considered to be related to the occurrence of cardiovascular diseases. Currently, MPO is considered the most promising cardiovascular marker. The increase in MPO content in the body indicates the risk of atherosclerosis and coronary heart disease. It is an early warning sign of myocardial infarction and is more sensitive than other indicators such as troponin T, CK-MB and CRP for early diagnosis and risk assessment. The level of MPO can be significantly increased within 2 hours after chest pain occurs. Therefore, for patients with chest pain, MPO will have more important clinical significance for diagnosing acute coronary syndrome (ACS).

H-FABP/FABP3 is a new type of cytoplasmic protein in the heart and one of the most abundant proteins in the heart muscle cells, accounting for 4%-8% of the total soluble protein in the myocardial cells. After an acute myocardial infarction (AMI), H-FABP is released more quickly from myocardial cells than myoglobin, and can be detected in the blood as early as 1-3 hours after chest pain onset, reaching its peak at 6-8 hours and returning to normal within 12-24 hours. It has high sensitivity and good specificity in early AMI diagnosis. H-FABP has a high degree of myocardial specificity compared to MYO, with a myocardial specificity that is 15-20 times that of myoglobin. In addition, the normal serum/plasma value of H-FABP is lower than that of myoglobin, thereby reducing the false positive rate. Therefore, H-FABP replaces MYO as an ideal marker for early diagnosis of myocardial infarction and will become a trend. In addition to early diagnosis of AMI, H-FABP is used to monitor the degree of myocardial infarction and reperfusion injury after cardiac surgery. The concentration of H-FABP can effectively identify high-risk patients with adverse events such as AMI, heart failure, and unstable angina pectoris in ACS long-term prognosis; combined detection with myoglobin can improve diagnostic sensitivity and is more valuable for ACS diagnosis.

NT-proBNP is the N-terminal fragment of BNP hormone that is not active after BNP precursor is cleaved. Compared with BNP, NT-proBNP has a longer half-life and is more stable. Its concentration can reflect the release of newly synthesized rather than stored BNP within a short period of time, and therefore can better reflect the activation of the BNP pathway. Plasma NT-proBNP levels increase with the severity of heart failure. NT-proBNP <300 pg/ml is normal and can exclude heart failure, with a negative predictive value of 99%. NT-proBNP helps to distinguish between cardiac and non-cardiac dyspnea; the level of NT-proBNP is related to the severity of symptoms in patients with heart failure accompanied by dyspnea.

Troponin is a group of contractile proteins that exist in skeletal muscle and cardiac muscle cells. Cardiac troponin (cTn) is a group of proteins related to cardiac contractile function in the troponin complex. It consists of three subunits: troponin T (TnT, which is part of the regulatory protein), troponin I (Tnl, which contains an inhibitory factor and is not expressed in skeletal muscle), and troponin C (TnC, a calcium-binding protein), all of which are encoded by different genes. TnT and TnI are heart-specific antigens. When myocardial injury or necrosis occurs, the serum cTn level increases due to increased myocardial cell permeability and/or degradation of cTn from myocardial fibers. Therefore, changes in serum cTn concentration are of great value in diagnosing the severity of myocardial ischemic injury and can be measured using specific anti-cTnT and cTnl antisera.

Myoglobin (MYO) is a protein that stores and distributes oxygen in mammalian cells. Myoglobin consists of a polypeptide chain and a heme group, with a relative molecular mass of 16.7 kDa and 153 amino acid residues. It is mainly distributed in cardiac and skeletal muscle tissues. Myoglobin without heme is called globin. It has significant homology with the subunits of hemoglobin (α-globin chain and β-globin chain) in amino acid sequence, and their conformation and function are also very similar. Myoglobin is widely distributed in cardiac and skeletal muscles, and its content in normal human blood is very low. When myocardial and skeletal muscles are damaged, the MYO level in the blood increases significantly. Therefore, MYO measurement is helpful for the diagnosis of acute myocardial infarction. At the same time, it is necessary to grasp the analysis of abnormal results. Within 4-12 hours after the onset of myocardial infarction, the serum myoglobin level can reach its peak, and it will return to normal after 48 hours. It is an early indicator for the diagnosis of myocardial infarction. However, serum myoglobin can also increase in patients with skeletal muscle diseases, shock, surgical trauma, or renal failure, so it needs to be distinguished; patients with pseudohypertrophic muscular dystrophy, acute dermatomyositis, polymyositis, etc., have parallel increases in myoglobin and creatine kinase levels.

Creatine kinase (CK) is a dimer composed of a brain-type subunit (B) and a muscle-type subunit (M). There are four isoenzymes of CK (Creatine Kinase Isoenzymes) in normal human tissues, which are arranged in order of electrophoretic speed: brain-type CK-BB (CK1), hybrid-type CK-MB (CK2), muscle-type CK-MM (CK3), and mitochondrial CK-MiMi. The molecular weight of CK-MB is 85 kDa. It mainly exists in cardiac muscle tissue and accounts for 0-4% of CK in serum. There are two subtypes of CK-MB, including MB2 (tissue form) and MB1 (conversion form). After being released from the myocardium, the carboxyl-terminal end of CK-MB2 is hydrolyzed by plasma carboxypeptidase N to remove one lysine residue and convert it to the serum-modified subtype CK-MB1. CK and CK-MB are sensitive indicators of myocardial tissue damage, especially CK-MB is more specific. Elevated serum CK-MB is common in acute myocardial infarction, skeletal muscle injury, trauma, and strenuous exercise. Some members of malignant hyperthermia patients and their families also have elevated serum CK-MB. Serum CK-MB can be significantly increased in patients with rhabdomyosarcoma. In addition, heart surgery that damages the myocardium can cause transient elevation of CK-MB, which generally returns to normal within 24 hours after surgery.

Galectin-3 belongs to the galectin family. Gal-3 exists in activated myocardial macrophages and is expressed at low levels in normal human hearts. However, higher levels of Gal-3 can be detected in myocardial fibrosis and heart failure.

Apolipoprotein is the protein part of plasma lipoproteins, which can bind and transport blood lipids to various tissues of the body for metabolism and utilization. It can be divided into five types: A, B, C, D, and E. It is generally synthesized in the liver. Apolipoprotein A1 is the main apolipoprotein of high-density lipoprotein. If apolipoprotein A1 is reduced, it can be seen in patients with liver dysfunction, atherosclerosis, diabetes, and hyperlipidemia. The increase of apolipoprotein A1 can be affected by drugs, such as taking antiepileptic drugs; excessive drinking, pregnancy, chronic hepatitis, etc.

ST2 detection can reflect the process of myocardial fibrosis, which is of great significance for risk stratification and treatment of heart failure, and is helpful for the diagnosis of chronic heart failure, acute decompensated heart failure and other diseases. ST2 is a protein produced by cardiomyocytes after biomechanical stimulation. ST2 has two types:soluble growth stimulation expression gene 2 protein and transmembrane form growth stimulation expression gene 2 protein. In general, the level of ST2 is mostly determined according to the former, which is almost not affected by age, gender, body mass index, cause of heart failure, atrial fibrillation and other factors, and can help detect chronic heart failure and acute decompensated heart failure.