Endothelial dysfunction and C-reactive protein are risk factors for diabetes in essential hypertension

OBJECTIVE: Type 2 diabetes and essential hypertension are major risk factors for cardiovascular diseases. Endothelial dysfunction is an early step in the development of atherosclerosis and has been demonstrated in hypertensive and diabetic patients. RESEARCH DESIGN AND METHODS: We designed this study to determine whether forearm endothelial dysfunction is an independent predictor of type 2 diabetes in patients with essential hypertension. We enrolled 400 white never-treated hypertensive outpatients, free of type 2 diabetes at the time of the first evaluation. Endothelium-dependent vasodilation was investigated by intra-arterial infusion of acetylcholine. Insulin resistance was estimated by homeostasis model assessment. RESULTS: During the follow-up (4.5 +/- 1.6 years), 44 patients developed type 2 diabetes. The event rate was 2.4 events/100 patient-years. In a multivariate Cox regression analysis, the peak percentage increase in acetylcholine-stimulated forearm blood flow (hazard ratio [HR] 0.77 [95% CI 0.61-0.99]; P = 0.04) and C-reactive protein (1.16 [1.03-1.32]; P = 0.01) resulted in the only independent predictors of type 2 diabetes. CONCLUSIONS: An impaired vasodilatory response to acetylcholine predicts development of type 2 diabetes in patients with essential hypertension. Present data also extend recent findings regarding a possible inflammatory pathogenesis of type 2 diabetes and suggest a new approach in treatment of essential hypertension.