Studies of recurrent coronary events in obese postinfarction patients show mixed results despite potential importance of obesity-related pathophysiologic processes and associated markers in establishing and predicting risk. The study aim was to determine specific markers of recurrent risk in obese postinfarction patients. Nondiabetic patients of the Thrombogenic Factors and Recurrent Coronary Events (THROMBO) postinfarction study were classified according to BMI as normal weight (<25 kg/m(2)), overweight (25.0-29.9 kg/m(2)), and obese (> or = 30 kg/m(2)). Cox multivariable regression with adjustment for significant clinical covariates was performed in each group monitoring outcome (cardiac death, myocardial infarction (MI), or unstable angina with 26 months follow-up) as a function of 17 thrombogenic, inflammatory, and metabolic blood markers and 17 cardiovascular disease-associated genetic polymorphisms. Results revealed no statistically significant genetic or blood marker variables in normal or overweight patients. For obese postinfarction patients, elevated lipoprotein(a) (Lp(a))was found to be a highly significant risk marker with hazard ratio and 95% confidence interval of 3.94 (2.11-7.35), P = 0.000017 (upper tertile vs. lower two tertiles). Additionally, elevated Lp(a) was found to interact with the -75G>A polymorphism of the apolipoprotein A-I gene and the -250G>A polymorphism of the hepatic lipase gene in establishing risk. We conclude that interactions of elevated Lp(a) with polymorphisms of the apolipoprotein A-I and hepatic lipase genes, primarily reflective of altered lipoprotein metabolism, play an important role in the establishment of recurrent coronary event risk in obese, nondiabetic postinfarction patients. These findings suggest close monitoring and consideration of weight reduction for obese postinfarction patients with elevated Lp(a) levels.