Elevated Myocardial Enzymes after CABG Are Associated with Increased Mortality Risk, Study Says

A new analysis of creatine kinase (CK-MB) and troponin levels in patients who received coronary artery bypass graft (CABG) surgery found that elevated levels of the myocardial enzymes within 24 hours after surgery were associated with an increased intermediate and long-term mortality risk for patients. The results of the analysis, which compiled data from 7 different studies, were recently reported in the Journal of the American Medical Association [2011;305(6):585-591]. Each year approximately 400,000 CABG procedures are performed in the United States, and often there is an increase in patient CK-MB or troponin levels following surgery. According to the authors of the latest analysis, previous research has indicated that these elevated myocardial enzymes may be associated with a worse patient prognosis; however, research into this area has been limited. To investigate further, researchers designed an analysis of previous studies that evaluated mortality and either CK-MB, troponin levels, or both in patients who had recently undergone CABG. The purpose of the analysis was to quantify the relationship between elevated myocardial enzymes after surgery and early, intermediate, and long-term mortality. Researchers identified eligible studies by searching the PubMed database for studies where CABG surgery was performed, enzyme CK-MB data were available, and follow-up data for at least 3 months were included. The analysis ultimately included 7 studies following a total of 18,908 patients. The studies had follow-up times ranging from 3 months to 5 years. As part of the analysis, researchers calculated a CK-MB ratio for each patient by determining the ratio between the peak CK-MB level and the upper limit of normal (ULN) for the participating laboratory of each study. Researchers also assessed the relationship between the CK-MB ratio and long-term mortality by using a Cox proportional hazards model to measure mortality up to 30 days, from 30 days to 1 year, and from 1 to 5 years. A primary outcome of the study was mortality risk. Researchers found that mortality increased as patient CK-MB ratios increased and calculated the following 30-day survival rates based on CK-MB ratio categories: 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. Using a Cox model, researchers also found that the CK-MB ratio, age, history of renal dysfunction, and prior myocardial infarction were all significant predictors of 30-day mortality; however, the CK-MB ratio was the strongest predictor and remained strong even after adjusting for other baseline factors (χ²=143; P<.001; hazard ratio [HR] for each 5-point increase above the ULN=1.12; 95% CI, 1.10-1.14). Researchers also examined troponin levels and found that this enzyme was also independently associated with an increased risk of mortality (χ²=142 for 0-30 days and χ²=40 for 30 days to 6 months, both P<.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). They noted, however, that troponin measures were only provided in 2 of the studies. The authors of the analysis believe that their findings may have important implications for future clinical trials, but also acknowledge that there were several limitations to the analysis. For instance, some applicable studies may not have been included in the analysis, researchers were only able to adjust for confounders that corresponded to data available in all studies, and long-term follow-up was only included in 3 studies. They believe additional research will be needed to confirm the findings of the analysis.