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Original Contribution
February 9, 2011

Association of Myocardial Enzyme Elevation and Survival Following Coronary Artery Bypass Graft Surgery

Author Affiliations

Author Affiliations: The Mount Sinai Cardiovascular Institute, New York, New York (Drs Domanski and Farkouh); Duke Clinical Research Institute, Duke University Medical Center, Durham, North Carolina (Drs Mahaffey, Hasselblad, Smith, and Alexander, Mr Broderick, and Ms Pieper); New York Methodist Hospital, Brooklyn (Dr Brener); The George Institute for International Health, Sydney, Australia (Dr Hillis); Mercy Saint Vincent Medical Center, Toledo, Ohio (Dr Engoren); Emory University School of Medicine, Atlanta, Georgia (Dr Levy); Saint Louis University School of Medicine, St Louis, Missouri (Dr Chaitman); Baylor Healthcare System, Dallas, Texas (Dr Mack); and University Health Network and Li Ka Shing Knowledge Institute, University of Toronto, Toronto, Ontario, Canada (Dr Farkouh).

JAMA. 2011;305(6):585-591. doi:10.1001/jama.2011.99
Abstract

Context Several small studies have suggested that cardiac enzyme elevation in the 24 hours following coronary artery bypass graft (CABG) surgery is associated with worse prognosis, but a definitive study is not available. Also, the long-term prognostic impact of small increases of perioperative enzyme has not been reported.

Objective To quantify the relationship between peak post-CABG elevation of biomarkers of myocardial damage and early, intermediate-, and long-term mortality, including determining whether there is a threshold below which elevations lack prognostic significance.

Data Sources Studies (randomized clinical trials or registries) of patients undergoing CABG surgery in which postprocedural biomarker and mortality data were collected and included. A search of the PubMed database was performed in July 2008 using the search terms coronary artery bypass, troponin, CK-MB, and mortality.

Study Selection Studies evaluating mortality and creatine kinase (CK-MB), troponin, or both were included. One study investigator declined to participate and 3 had insufficient data.

Data Extraction 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, we 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.

Results A total of 18 908 patients from 7 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 < .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 < .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 = .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 < .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 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.

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