CK-MB is the "gold standard" and most commonly used marker for the diagnosis of AMI. In the setting of AMI, CK-MB levels rise to twice normal at 6 h and peak within approximately 24 h. Serial CK-MB measurement has a sensitivity of over 90 percent 3 h after ED presentation (approximately 5 to 6 h after symptom onset); it is only 50 percent sensitive when utilized at or shortly after presentation. —I! and 12 Patients with skeletal muscle disease, acute muscle exertion, chronic renal failure, and cocaine use often have elevated levels of CK-MB in the absence of infarction.
CK-MB2 is the subform that is released from the myocardium. Following release, it is cleaved by lysine carboxypeptidase, producing a more negatively charged molecule, CK-MB!. Normally both subforms are in equilibrium. When CK-MB 2 is greater than 1.0 U/L or the MB2:MB-, ratio is >1.5, the sensitivity and specificity for the diagnosis of AMI is improved. When serial sampling every 30-60 min is used, CK-MB subforms have a sensitivity for detection of AMI of 96 percent and a specificity of 93 to 96 percent within 6 h of ED arrival. Less frequent sampling has resulted in less impressive results. 13 The value of CK-MB subforms for the risk stratification of patients with acute coronary syndromes is unknown. The main advantage of CK-MB subform analysis is that it can identify patients with AMI earlier than CK-MB.
The troponin complex is the main regulatory protein of the thin filament of the myofibrils that regulate the Ca 2+-dependent ATP hydrolysis of actomyosin. The troponin complex consists of three subunits: an inhibitory subunit (troponin I), a tropomyosin binding subunit (troponin T), and a calcium-binding subunit (troponin C). Because each subunit has cardiac, slow-twitch, and fast-twitch skeletal isoforms, immunoassays based upon the significant heterogeneity in amino acid sequences can detect the specific isoforms. The cardiac isoform of troponin I is not found in skeletal muscle during any stage of development. As a result, elevations of cardiac troponin I do not occur in the setting of acute or chronic skeletal muscle damage unless concurrent myocardial necrosis is present.
Following AMI, cardiac troponin I becomes elevated after approximately 6 h, peaks at 12 h, and remains elevated for 7 to 10 days. Troponin I has a higher specificity for myocardial necrosis than CK-MB in selected subsets of patients with acute coronary syndromes such as those with recent surgery, cocaine use, chronic renal failure, and skeletal muscle disease.14 In ED patients with symptoms of acute coronary syndromes, cardiac troponin I has been shown to have similar sensitivity and specificity for detection of acute myocardial infarction as CK-MB.1 l6 and 17 In patients with acute coronary syndromes, elevations in cardiac troponin I values predict cardiovascular complications independent of CK-MB and the ECG.1 17 The cardiac specificity of troponin I is clearly an advantage, especially when CK-MB elevations are suspected to be false.
The cytosolic component of cardiac troponin T is released from the cell within 2 to 6 h following symptom onset. Its diagnostic sensitivity for AMI approaches 100 percent 10 h after symptom onset and it remains elevated for 7 to 10 days after injury. This extended period of elevation results from disintegration of the contractile apparatus and the continued release of cardiac troponin T. It is not as specific for myocardial injury as cardiac troponin I. It may be elevated in patients with renal disease who do not have acute coronary syndromes. Cardiac troponin T is an independent marker of cardiovascular risk in patients with acute coronary syndromes.1 I8 Risk can be further stratified when cardiac troponin T is combined with the ECG and CK-MB. However, the lower specificity of troponin T compared with cardiac troponin I is a disadvantage.
Myoglobin has a lower molecular weight and is released more rapidly than CK-MB during AMI. As a result, serum myoglobin levels rise faster than CK-MB, reaching twice normal values within 2 h and peaking within 4 h of AMI symptom onset. The sensitivity of older assays was poor. The newer monoclonal immunoassay techniques demonstrate higher sensitivity and specificity of myoglobin for AMI than older assays in patients presenting within 3 h of symptom onset. Serial quantitative testing with an immunochemical assay for myoglobin has 91 percent sensitivity and up to a 99 percent negative predictive value for AMI within 1 h of ED presentation (approximately 3 to 4 h after symptom onset).19 The advantage of myoglobin is early detection of patients with acute myocardial infarction. The disadvantage is that it has poor specificity for AMI in patients with concurrent trauma renal failure, rhabdomyolysis, and various hemolytic syndromes.
Evaluation of the myoglobin/carbonic anhydrase III ratio can enhance the specificity of myoglobin. 20 Carbonic anhydrase III is released from skeletal muscle in a fixed ratio with myoglobin. Combined assays can therefore help determine whether myoglobin is of skeletal or cardiac origin. With use of these dual assays, the high early sensitivity of myoglobin is maintained and specificity is improved. These assays are not yet commercially available. The use of dual assays for risk stratification has not yet been evaluated.
Other cardiac markers, such as glycogen phosphorylase BB and myosin light chains, are currently being evaluated. In addition, markers of platelet activation such as P-selectin and other integrins are theoretically attractive as indicators of acute coronary syndrome. They might detect platelet activation prior to myocardial injury. Their role in the diagnosis and triage of patients with acute coronary syndromes remains to be determined.
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