Insulin resistance increases the occurrence of new cardiovascular events in patients with manifest arterial disease without known diabetes. The SMART study

Background: Insulin resistance is accompanied by a cluster of metabolic changes, often referred to as metabolic syndrome. Metabolic syndrome is associated with an increased cardiovascular risk in patients with manifest arterial disease. We investigated whether insulin resistance is associated with an increased risk for cardiovascular events in patients with manifest arterial disease without known diabetes and whether this can be explained by the components of the metabolic syndrome or by inflammation. Methods: Prospective cohort study in 2611 patients with manifest arterial disease without known diabetes. Homeostasis model of insulin resistance (HOMA-IR) was used to quantify insulin resistance. The relation of HOMA-IR with cardiovascular events (vascular death, myocardial infarction or stroke) and all cause mortality was assessed with Cox regression analysis. In additional models adjustments were performed for the single components constituting the metabolic syndrome and for inflammation. Results: HOMA-IR increases with the number of metabolic syndrome components (mean HOMA-IR +/- SD in groups with 0, 1, 2, 3, 4 and 5 metabolic syndrome components: 1.4 +/- 0.7; 1.8 +/- 1.2; 2.4 +/- 1.5; 3.1 +/- 1.8; 4.0 +/- 2.6; and 5.6 +/- 3.6 respectively). High HOMA-IR was independently associated with an increased risk of cardiovascular events (tertile 2 vs. 1 HR 1.92; 95% CI 1.20-3.08) (tertile 3 vs. 1 HR 1.78; 95% CI 1.10-2.89) and with all cause mortality (tertile 2 vs. 1 HR 1.80; 95% CI 1.04-3.10) (tertile 3 vs. 1 HR 1.56; 95% CI 0.88-2.75). These relations were not influenced by the individual components of metabolic syndrome or by inflammation. Conclusions: In patients with manifest arterial disease without known diabetes, insulin resistance increases with the number of metabolic syndrome components, and elevated insulin resistance increases the risk of new cardiovascular events.