Endothelial Dysfunction and C-Reactive Protein Are Risk Factors for Diabetes in Essential Hypertension
- Francesco Perticone1,
- Raffele Maio1,
- Angela Sciacqua1,
- Francesco Andreozzi1,
- Giuseppina Iemma1,
- Maria Perticone1,
- Carmine Zoccali2 and
- Giorgio Sesti1
- 1Department of Experimental and Clinical Medicine “G. Salvatore,” University Magna Græcia of Catanzaro, Catanzaro, Italy
- 2Clinical Epidemiology and Physiopathology of Renal Diseases and Hypertension, CNR-IBIM, Reggio, Calabria, Italy
- Address correspondence and reprint requests to Francesco Perticone, MD, Department of Experimental and Clinical Medicine, Campus Universitario di Germaneto, V. le Europa, 88100 Catanzaro, Italy. E-mail: perticone{at}unicz.it
Abstract
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.
Footnotes
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Published ahead of print at http://diabetes.diabetesjournals.org on 10 October 2007. DOI: 10.2337/db07-1189.
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The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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- Accepted October 4, 2007.
- Received August 23, 2007.
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