Creatine kinase isoenzyme MB mass, cardiac troponin T, and myosin light chain isotype 1 as serological markers of myocardial injury and their prognostic importance in acute coronary syndrome.

Acute coronary syndrome encompasses the entities acute MI, unstable AP and sudden cardiac death. The syndrome of unstable AP covers a very heterogenous group of patients. Recent pathological post-mortem investigations have revealed, that unstable AP leading to MI or sudden cardiac death is frequently preceded by microinfarctions. Despite the fact that thrombus formation is recognized as the major cause, the role of coronary artery spasm seems also important. Therefore, the pathological hallmark of ACS is at present thought to be caused by an active coronary plaque (the culprit lesion), which is often the site of intermittent occlusion and of thrombus formation, with or without vasospasm. The release of myocardial cell constituents in connection with these microinfarctions is to be expected. In order to detect these, diagnostic tools sensitive to myocardial injury and specific for myocardial tissue must be employed. According to WHO the criteria for the diagnosis of acute MI are based on clinical history, electrocardiographic changes, and enzymes in serum. Although these criteria are quite adequate in most cases, they are not present or easily discernible in all acute MI patients. The clinical symptoms are and will remain insensitive and nonspecific indicators of acute MI. Electrocardiographic alterations are carefully described, but sometimes less applicable due to non-interpretable ECG's. During the last decades, activity measurements of cardiac enzymes, and especially the isoenzymes of CK and LD, have become the final arbiters by which myocardial damage is diagnosed or excluded. However, they are not fully cardiospecific and have a low sensitivity to detect MMI, retaining a high specificity. Improved immunoassays have therefore been developed measuring the mass concentration of CK-MB instead of its catalytic activity, as well as immunoassays measuring structural proteins of the heart i.e., TnT, a tropomyosin-binding protein of the troponin regulatory complex located on the thin filament of the contractile apparatus of the myocyte; and MLC, a component of the thick filament of the contractile apparatus of the myocyte. We, and others, have shown that minor ischaemic myocardial injury can be detected by CK-MB mass immunoassays in around one-fourth to one-third of patients with unstable AP or in whom an acute MI has been ruled out. However, the prognostic significance of this identification has not been investigated. A priori, it is known that 5-20% of patients with unstable AP have a poor prognosis, with progression to acute MI or cardiac death within the first year. Additional, non-Q wave MI may also be considered a relatively unstable condition associated with a lower initial mortality but a higher risk of later MI/cardiac death. It is of further importance, that although the incidence of unrecognized MI is less than that of clinically apparent MI, the long-term prognosis for unrecognized MI appears to be similar to, and as serious as, that following detected MI. Therefore, in order to follow-up this subgroup identification based on CK-MB mass levels, we subsequently carried out a prognostic study. It demonstrated a significantly increased risk of cardiac events (i.e., non-fatal acute MI, cardiac death) in patients with significant fluctuations of CK-MB mass in serum. A similar observation has been supported by others using the rate of change in serial samples of CK-MB mass. Further, we demonstrated a good correlation between elevated CK-MB mass levels and a poor prognosis, when using a fixed discrimination limit. However, an increasing number of CK-MB mass immunoassays have been developed, and a standardization of CK-MB mass is urgently needed, as at present each laboratory determines its own reference levels and discriminatory values leading to the risk of diagnostic confusion. (ABSTRACT TRUNCATED)