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J Thorac Cardiovasc Surg 2010;139:483-488
© 2010 The American Association for Thoracic Surgery

Perioperative Management

Common genetic variants on chromosome 9p21 predict perioperative myocardial injury after coronary artery bypass graft surgery

^a Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Mass
^b Baylor College of Medicine, Division of Cardiovascular Anesthesia, The Texas Heart Institute, Saint Luke's Episcopal Hospital, Houston, Tex

Received for publication February 25, 2009; revisions received May 20, 2009; accepted for publication June 20, 2009.

^_* Address for reprints: Jochen D. Muehlschlegel, MD, Department of Anesthesiology, Perioperative and Pain Medicine, CWN L1, Brigham and Women's Hospital, 75 Francis St, Boston, MA 02115. (Email: jmuehlschlegel{at}partners.org).

Objective: Approximately 10% of patients undergoing cardiac surgery have perioperative myocardial injury. A recent genome-wide association study identified an association between myocardial infarction in nonsurgical populations and common genetic variants on chromosome 9p21. We hypothesized that these variants are also associated with perioperative myocardial injury after isolated primary coronary artery bypass graft surgery.

Methods: In a prospective observational study of 846 Caucasian patients undergoing primary coronary bypass surgery at 2 US centers, we genotyped 61 linkage-disequilibrium tagging single nucleotide polymorphisms, encompassing 436 kbp of the 9p21 region. A multivariable logistic model was used to adjust for previously identified clinical covariates of perioperative myocardial injury. Perioperative myocardial injury was defined as a postoperative day 1 cardiac troponin I in the top 10th percentile (>9.13 µg/L) of the cohort. Multiple testing of single nucleotide polymorphisms was corrected for with family-wise errors.

Results: Prior myocardial infarction and longer cardiopulmonary bypass time were significant independent predictors of perioperative myocardial injury. Levels of postoperative cardiac troponin I were incrementally increased for each additional copy of the risk alleles of 3 single nucleotide polymorphisms: rs10116277, rs6475606, and rs2383207. Adjusted additive odds ratios ranged between 1.64 and 1.79 (asymptotic P value between 3.7 x 10^–3 and 6 x 10^–4) and remained significantly associated with perioperative myocardial injury even after accounting for clinical covariates including severity of coronary disease, and multiple comparisons.

Conclusions: We have now demonstrated that common genetic variants in the same 9p21 locus, previously known to be associated with myocardial infarction in nonsurgical populations, are also associated with perioperative myocardial injury after coronary artery bypass grafting. Further investigation is warranted to elucidate functional mechanisms.