Minor CK-MB Elevations Not so Minor After All

abstract & commentary

Source: Alexander JH, et al. Association between minor elevations of creatine kinase-MB level and mortality in patients with acute coronary syndromes without ST-segment elevation. JAMA 2000;283:347-353.

The criteria used to diagnose myocardial infarction (MI) have remained the same for 20 years. These criteria require the presence of at least two of the following three elements to diagnose MI: a history of ischemic-type chest discomfort, evolutionary changes on serial electrocardiograms, and a rise and fall in serum cardiac enzymes. The authors used the 9461 patients enrolled in the PURSUIT trial to evaluate the relationship between peak CK-MB level (as an estimate of infarct size) and outcome, to determine whether a threshold CK-MB elevation exists below which there is no increased risk for mortality. The PURSUIT trial compared placebo to the glycoprotein IIb/IIIa inhibitor eptifibatide (Integrilin) for patients with cardiac chest pain without ST-elevation. Mortality at 30 days and six months was assessed according to peak CK-MB level (0-1, > 1-2, > 2-3, > 3-5, > 5-10, or >10 times the upper limit of normal). Mortality at 30 days and six months increased from 1.8% and 4.0% respectively in patients with normal peak CK-MB levels to 3.3% and 6.2% at peak CK-MB levels 1-2 times normal; to 5.1% and 7.5% at peak CK-MB levels 3-5 times normal; and to 8.3% and 11.0% at peak CK-MB levels greater than 10 times normal. In conclusion, this study demonstrates that in patients with cardiac chest pain without ST-segment elevation, a strong relationship exists between the magnitude of CK-MB elevation and mortality, and the risk begins just above the upper limit of normal. Alexander and associates go on to state that small CK-MB elevations represent clinically important evidence of myocardial necrosis and should be considered sufficient cardiac-marker criteria for a diagnosis of MI in patients with cardiac chest pain. Elevation of CK-MB above the upper limit of normal identifies a group of patients at higher risk of death.

Comment by Richard J. Hamilton, MD, FAAEM, ABMT

The number of laboratory tools for finding the sick cardiac patients in the emergency center has grown in recent years. For example, since adding troponin I to our cardiac enzyme panel, I have identified a significant number of patients with myocardial infarction that I may have overlooked with simple isoenzymes and ECG findings. This article provides insight into another laboratory tool—the total CK-MB. Alexander et al provide solid evidence that one elevated total CK-MB seems to have some utility as a predictor of short-term mortality and probably should be regarded as evidence of acute MI. In my practice, that means I should be more aggressive when a patient with cardiac chest pain has a single elevated CK-MB, even with an ECG without acute injury pattern. Furthermore, I might be able to gauge the level of intervention on the degree to which the CK-MB is elevated. No data are available to show that a particular intervention (such as thrombolysis) may be beneficial, but this will guide the other difficult decisions we make everyday about the use of heparin, beta blockers, or intravenous nitrates in cardiac chest pain. Perhaps the 20-year-old World Health Organization guidelines need reconsideration, but I’ll accept these data as a reason to lower my threshold for action now.

23. Elevations of CK-MB:

a. are meaningless unless accompanied by EKG changes suggestive of acute myocardial infarction.

b. are meaningless unless present on consecutive serum samples.

c. may represent clinically significant myocardial necrosis.

d. may represent clinically significant myocardial necrosis only if they are elevated 10 times normal.