Insulin resistance is associated with increased risk of major cardiovascular events in patients with preexisting coronary artery disease

Background Over the past years it has been recognized that insulin resistance (IR) is an independent risk factor for the development of diabetes, whereas its association with cardiovascular events remains controversial. The aim of our study was to explore the association between IR per se and cardiovascular events among patients with preexisting coronary artery disease. Methods The mean follow-up period of this prospective study was 6.2 years. Metabolic and inflammatory parameters were analyzed from stored frozen plasma samples obtained at baseline from 2938 patients aged 45 to 74 years. The homeostatic index of IR (HOMA-IR) was calculated according to the homeostasis model assessment. Results New major cardiovascular events (fatal and nonfatal myocardial infarction and sudden death) were recorded in 108 (11.1%) patients from the lowest IR tertile, in 147 (14.7%) from the intermediate tertile, and in 166 (17.2%) from the highest tertile (P = .0002). The linear trend for total and cardiac death across the tertiles of HOMA-IR was significant as well (P = .02 and P = .009, respectively). The highest age-adjusted rates for major cardiovascular events and new diabetes were found among patients within the top tertile of HOMA-IR (57% and 130% higher rates, respectively, tertile 3 vs tertile 1, P < .0001 for both). Multivariable analysis identified HOMA-IR (tertile 3 vs tertile 1) as an independent predictor of increased risk of major cardiovascular events and new diabetes with hazard ratios (95% CI) of 1.4 (1.1-1.8) and 1.5 (1.1-2.0), respectively. Conclusions Insulin resistance per se is an independent risk factor for cardiovascular events and new diabetes in patients with preexisting coronary artery disease.