Platelet gene polymorphisms and cardiac risk assessment in vascular surgical patients

Background: Current perioperative cardiac risk assessment tools use historic and surgical factors to stratify patient risk. Polymorphisms in platelet glycoprotein (GP) IIIa and GPIbα are associated with myocardial ischemic risk in nonsurgical settings, but their relation to perioperative ischemia is unclear. The authors hypothesized that platelet genotype would be an independent predictor of postoperative myocardial ischemia and would improve risk assessment when added to clinical factors. Methods: One hundred ninety-six patients who underwent infrainguinal, abdominal aortic, or thoracoabdominal vascular surgery were evaluated for clinical and genetic factors that might predict the development of postoperative myocardial ischemia. Genomic DNA was genotyped for the Leu33Pro polymorphism of GPIIIa and the Thr145Met polymorphism of GPIbα. Myocardial ischemic outcome was determined by review of the medical record for cardiac death or myocardial infarction and by surveillance troponin I and automated continuous 12-lead electrocardiographic analysis. Results: Sixty-five patients (33%) experienced one or more ischemic endpoints (2% death, 5% myocardial infarction, 20% troponin+, 22% electrocardiogram+). The Pro33 (adjusted odds ratio [OR], 2.4 [95% confidence interval, 1.2-6.2]) and Met145 (OR 3.4 [1.4-9.3]) genotypes were independent predictors of composite ischemic outcome by multivariate regression, as were diabetes mellitus (OR 4.0 [1.7-12.5]), abdominal aortic surgery (OR 4.1 [1.7-14.4]), and thoracoabdominal aortic surgery (OR 6.4 [2.7-23.8]). The addition of platelet gene polymorphisms to clinical factors improved fit (likelihood ratio testing chi-square = 13.5, P < 0.001) of an ischemia prediction model. The derived risk assessment tool had a receiver operator characteristic curve of 0.73 (0.65-0.81) compared with 0.64 (0.57-0.74) for a model excluding genetic factors (P = 0.04). A significant relation between the GPIbα polymorphism and ischemic outcome remained after excluding electrocardiographic ischemia from the composite endpoint. Conclusions: Platelet polymorphisms are independent risk factors for postoperative myocardial ischemia and improve a risk prediction model when added to historic and surgical risk factors.