Enzyme, Isoenzyme, and Biochemical Markers



  • The diagnostic utilization of cardiac markers has evolved dramatically over the past 50 years; however, no ideal cardiac marker has been identified.




  • When myocardial tissue is damaged (eg, due to MI), cellular injury results in the release of intracellular enzymes and proteins (cardiac enzymes, isoenzymes, and biochemical markers) into the bloodstream which, in turn, causes elevated peripheral blood enzyme levels
    • The substances monitored for indication of cardiac damage or disease include:
      • Creatine kinase (CK) has a 98% sensitivity for AMI 72 hours after infarction. CK is a catalyst for energy production and is found in brain, myocardium, and skeletal muscle. CK is sensitive but not specific for myocardial injury.
      • CK isoenzymes are more specific than CK. Three CK isoenzymes have been identified: CK-MM, CK-MB, and CK-BB, with only CK-MB related to the heart. The specificity of CK-MB is greater than 85% and in some cases as high as 100%, but false positives do occur. Two types of CK-MB assays (CK-MB mass and CK-MB activity) are presently used. CK-MB mass assays are found to be more sensitive than CK-MB activity assays; CK-MB mass increases about 3 hours after onset of chest pain, whereas CK-MB activity requires another 1 hour to elevate. CK-MB index is the ratio of CK-MB to the total CK, and is considered abnormal when it exceeds 3% to 5%.
      • Eventually, electrophoresis further breaks down CK-MB into its isoforms or subforms (CK-MB1 and CK-MB2). Normally, the ratio of CK-MB2 to CK-MB1 is 1:1. In myocardial injury, the CK-MB2/MB1 ratio increases to greater than 1.5 within 1 to 1½ hours. CK-MB isoforms have 56% sensitivity for patients presenting within 4 hours of the onset of symptoms.
      • The troponin complex is located on the thin filament of the contractile apparatus of striated and skeletal muscle and consists of three subunits: troponin C (TnC), troponin T (TnT), and troponin I (TnI). In the presence of myocardial damage, the troponin complex on the myofibril breaks down and the subunits of troponin are slowly released into the bloodstream. TnC is not sensitive or specific for myocardial injury. TnT has a sensitivity of approximately 50% within 4 hours of the onset of chest pain, but increases to approximately 75% sensitivity after 6 hours of onset and approximately 100% sensitivity in 12 hours. However, its specificity for myocardial injury is lower. TnI has been found to be the most sensitive and specific for myocardial injury. It has little sensitivity within 4 hours of the onset of chest pain, but increases to 96% sensitivity after 6 hours of the onset of symptoms.
      • Myoglobin is a small, oxygen-binding protein found in cardiac and skeletal muscles and is rapidly released into the bloodstream. Myoglobin is sensitive very early after injury, but has poor sensitivity over time and can generate many false-positive results. When myoglobin levels are assessed with CK-MB results, sensitivity increases (as high as 96%), but specificity can drop to as low as 81%. Myoglobin is directly related to muscle mass and is affected by age (levels increase with age), race (blacks have higher levels), gender (women have higher levels), and physical activity. Myoglobins can be elevated in the presence of reinfarction, skeletal muscle or neuromuscular disorders, trauma, severe burns, electrical shock, alcohol withdrawal delirium, metabolic disorders, systemic lupus erythematosus, strenuous exercise, renal failure, I.M. injections, cardiac bypass surgery, seizures, and heart failure.
      • Homocysteine is a toxic by-product of the metabolism of the amino acid methionine into cysteine. Homocysteine exerts a direct cytotoxic effect on the endothelium of blood vessels by blocking the production of nitrous oxide, resulting in decreased pliability of vessels and the development of atherosclerotic plaque. Increased homocysteine levels ultimately result in atherosclerosis, CAD, MI, stroke, thromboembolism, and peripheral vascular disease. Hyperhomocystinemia (increased homocysteine levels) are related to gender (male), advanced age, smoking, hypertension, elevated cholesterol, decreased folate, decreased vitamin B6 and B12, and lack of exercise. Homocysteine can also be elevated in the presence of other diseases, drug use, and caffeine intake.
      • B-type natriuretic peptide (BNP) is synthesized in the ventricular myocardium and released as a response to increased wall stress. BNP is used for diagnosis and prognosis of suspected heart failure. Plasma levels of BNP increase in the presence of left ventricular systolic and diastolic dysfunction, particularly in the presence of decompensating heart failure. An increased BNP level identifies patients at the highest risk of developing sudden cardiac death and those who are in need of heart transplant. It is also associated with heart failure readmissions. BNP is considered a useful marker of myocardial function and is used to guide therapy.
      • C-reactive protein (CRP) is an inflammatory marker that may be an important risk factor for atherosclerosis and ischemic heart disease. CRP is an inflammatory marker produced by the liver in response to systemic cytokinases. Elevated CRP is associated with AMI, stroke, and the progression of peripheral vascular disease. However, it can also be elevated with any inflammatory process. In addition to revealing events associated with CAD, CRP can also be used to identify patients at risk for developing CAD.
      • Lipoprotein(a) is a molecule that is similar to low-density lipoprotein cholesterol (LDL-C). It increases cholesterol deposits in the arterial wall, enhances oxidation of LDL-C, and inhibits fibrinolysis, resulting in the formation of atherosclerotic plaque and thrombosis. Treatment of elevated lipoprotein(a) is suggested only for patients with a history of premature vascular disease without other risk factors.
      • Factor I, or fibrinogen, is directly linked to increased cardiovascular risk. It is involved in the coagulation cascade (converting fibrinogen to fibrin by thrombin), stimulates smooth-muscle cell migration and proliferation, and promotes platelet aggregation, which increases blood viscosity.
    Nursing and Patient Care Considerations
    • Make sure that enzymes are drawn in a serial pattern, usually on admission and every 6 to 24 hours until three samples are obtained; enzyme activity is then correlated with the extent of heart muscle damage.
    • Maintain standard precautions while obtaining blood specimens, and properly dispose of all equipment.
    • Advise patient that results will be discussed with him by the physician or primary care provider.
    Greater peaks in enzyme activity and length of time an enzyme remains at its peak level are correlated with serious damage of the heart muscle and a poorer prognosis for the patient.