Inflammatory gene polymorphisms and risk of postoperative myocardial infarction after cardiac surgery.

Journal Article (Journal Article)

BACKGROUND: The inflammatory response triggered by cardiac surgery with cardiopulmonary bypass (CPB) is a primary mechanism in the pathogenesis of postoperative myocardial infarction (PMI), a multifactorial disorder with significant inter-patient variability poorly predicted by clinical and procedural factors. We tested the hypothesis that candidate gene polymorphisms in inflammatory pathways contribute to risk of PMI after cardiac surgery. METHODS AND RESULTS: We genotyped 48 polymorphisms from 23 candidate genes in a prospective cohort of 434 patients undergoing elective cardiac surgery with CPB. PMI was defined as creatine kinase-MB isoenzyme level > or = 10x upper limit of normal at 24 hours postoperatively. A 2-step analysis strategy was used: marker selection, followed by model building. To minimize false-positive associations, we adjusted for multiple testing by permutation analysis, Bonferroni correction, and controlling the false discovery rate; 52 patients (12%) experienced PMI. After adjusting for multiple comparisons and clinical risk factors, 3 polymorphisms were found to be independent predictors of PMI (adjusted P<0.05; false discovery rate <10%). These gene variants encode the proinflammatory cytokine interleukin 6 (IL6 -572G>C; odds ratio [OR], 2.47), and 2 adhesion molecules: intercellular adhesion molecule-1 (ICAM1 Lys469Glu; OR, 1.88), and E-selectin (SELE 98G>T; OR, 0.16). The inclusion of genotypic information from these polymorphisms improved prediction models for PMI based on traditional risk factors alone (C-statistic 0.764 versus 0.703). CONCLUSIONS: Functional genetic variants in cytokine and leukocyte-endothelial interaction pathways are independently associated with severity of myonecrosis after cardiac surgery. This may aid in preoperative identification of high-risk cardiac surgical patients and development of novel cardioprotective strategies.

Full Text

Duke Authors

Cited Authors

  • Podgoreanu, MV; White, WD; Morris, RW; Mathew, JP; Stafford-Smith, M; Welsby, IJ; Grocott, HP; Milano, CA; Newman, MF; Schwinn, DA; Perioperative Genetics and Safety Outcomes Study (PEGASUS) Investigative Team,

Published Date

  • July 4, 2006

Published In

Volume / Issue

  • 114 / 1 Suppl

Start / End Page

  • I275 - I281

PubMed ID

  • 16820586

Pubmed Central ID

  • PMC1945056

Electronic International Standard Serial Number (EISSN)

  • 1524-4539

Digital Object Identifier (DOI)

  • 10.1161/CIRCULATIONAHA.105.001032


  • eng

Conference Location

  • United States