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Association of Myocardial Enzyme Elevation and Survival Following Coronary Artery Bypass Graft Surgery
Study Questions:
What is the relationship between peak post-coronary artery bypass grafting (CABG) elevation of biomarkers of myocardial damage and early, intermediate-, and long-term mortality?
Methods:
Studies (randomized clinical trials or registries) of patients undergoing CABG surgery, in which postprocedural biomarker and mortality data were collected, were included. A search of the PubMed database was performed in July 2008 using the search terms coronary artery bypass, troponin, creatine kinase-myocardial band (CK-MB), and mortality. Two independent reviewers determined study eligibility. The principal investigator from each eligible study was contacted to request his/her participation. Once institutional review board approval for the use of these data for this purpose was obtained, the authors requested patient-level data from each source. Data were examined to ensure that cardiac markers had been measured within 24 hours after CABG surgery, key baseline covariates, and mortality were available. To examine the longer-term relationship of the CK-MB and troponin ratio to mortality, the investigators fitted a Cox proportional hazards model for mortality from 0 to 30 days, 30 days to 1 year, and from 1 to 5 years.
Results:
A total of 18,908 patients from seven studies were included. Follow-up varied from 3 months to 5 years. Mortality was found to be a monotonically increasing function of the CK-MB ratio. The 30-day mortality rates by categories of CK-MB ratio were 0.63% (95% confidence interval [CI], 0.36%-1.02%) for 0 to <1, 0.86% (95% CI, 0.49%-1.40%) for 1 to <2, 0.95% (95% CI, 0.72%-1.22%) for 2 to <5, 2.09% (95% CI, 1.69%-2.57%) for 5 to <10, 2.78% (95% CI, 2.12%-3.58%) for 10 to <20, and 7.06% (95% CI, 5.46%-8.96%) for 20 to ≥40. Of the variables considered, the CK-MB ratio was the strongest independent predictor of death to 30 days and remained significant even after adjusting for a wide range of baseline risk factors (χ2 = 143, p < 0.001; hazard ratio [HR] for each 5-point increment above the upper limits of normal [ULN] = 1.12; 95% CI, 1.10-1.14). This result was strongest at 30 days, but the adjusted association persisted from 30 days to 1 year (χ2 = 24; p < 0.001; HR for each 5-point increment above ULN = 1.17; 95% CI, 1.10-1.24) and a trend was present from 1 year to 5 years (χ2 = 2.8; p = 0.10; HR for each 5-point increment above ULN = 1.05; 95% CI, 0.99-1.11). Similar analyses using troponin as the marker of necrosis led to the same conclusions (χ2 = 142 for 0-30 days and χ2 = 40 for 30 days to 6 months, both p < 0.001; HR for each 50 points above the ULN = 1.28; 95% CI, 1.23-1.33 and 1.15; 95% CI, 1.10-1.21, respectively).
Conclusions:
The authors concluded that among patients who had undergone CABG surgery, elevation of CK-MB or troponin levels within the first 24 hours was independently associated with increased intermediate- and long-term risk of mortality.
Perspective:
This large study of the relationship between post-CABG surgery enzyme elevation and mortality shows a strong, graded, independent association of elevation of CK-MB and troponin levels, and mortality following CABG surgery for all CK-MB and troponin ratios greater than 1. The mortality rate more than doubled at a CK-MB ratio of 4.4, and qualitatively similar results were seen for troponin elevation. These findings require confirmation in large prospective studies, and if confirmed, may influence the design of future clinical trials with respect to using cardiac markers as an outcome measure following CABG surgery. The appropriate threshold level for choosing an enzyme increase as a predictor of worse prognosis also needs to be prospectively defined in future studies.
Keywords: Outcome Assessment, Health Care, Prognosis, Follow-Up Studies, Proportional Hazards Models, Biomarkers, Creatine Kinase, MB Form, Risk Factors, Necrosis, Coronary Artery Bypass, Troponin
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