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Endothelial Dysfunction and CRP Are Risk Factors for Diabetes in Essential Hypertension

Francesco PERTICONE, MD^*, Raffaele MAIO, MD^*, Angela SCIACQUA, MD^*, Francesco ANDREOZZI, MD^*, Giuseppina IEMMA, MD^*, Maria PERTICONE, MD^*, Carmine ZOCCALI, MD, and Giorgio SESTI, MD^*

(*) Department of Experimental and Clinical Medicine "G. Salvatore", University Magna Græcia of Catanzaro, Italy;
() CNR-IBIM, Clinical Epidemiology and Physiopathology of Renal Diseases and Hypertension, 89100 Reggio Calabria, Italy

OBJECTIVE: Type-2 diabetes mellitus and essential hypertension are major risk factor 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 mellitus in patients with essential hypertension. We unrolled 400 white never treated hypertensive outpatients, free of type-2 diabetes mellitus at the time of the first evaluation. Endothelium-dependent vasodilation was investigated by intra-arterial infusion of acetylcholine. Insulin-resistance was estimated by the homeostasis model assessment (HOMA).

RESULTS: During the follow-up (4.5±1.6 years), 44 patients developed type-2 diabetes mellitus. Event rate was 2.4 events/100 patient-years. In a multivariate Cox regression analysis, the peak percent increase in acetylcholine-stimulated forearm blood flow (HR = 0.77, CI = 0.61-0.99; P=0.04) and CRP (HR = 1.16, CI = 1.03-1.32; P=0.01) resulted the only independent predictors of type-2 diabetes mellitus.

CONCLUSIONS: An impaired vasodilatory response to acetylcholine predicts the development of type-2 diabetes mellitus 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 the treatment of essential hypertension.

Key Words: endothelium • prediction and prevention • insulin resistance • hypertension

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