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(Circulation. 2001;104:191.)
© 2001 American Heart Association, Inc.

Clinical Investigation and Reports

Prognostic Significance of Endothelial Dysfunction in Hypertensive Patients

Francesco Perticone, MD; Roberto Ceravolo, MD; Arturo Pujia, MD; Giorgio Ventura, MD; Saverio Iacopino, MD; Angela Scozzafava, MD; Alessandro Ferraro, MD; Massimo Chello, MD; Pasquale Mastroroberto, MD; Paolo Verdecchia, MD; Giuseppe Schillaci, MD

From the Internal Medicine and Cardiovascular Diseases Unit (F.P., R.C., A.P, G.V., S.I., A.S., A.F.) and Cardiovascular Surgery Unit (M.C., P.M.), Department of Medicina Sperimentale e Clinica "G. Salvatore," University of Catanzaro Magna Græcia, Catanzaro, Italy, and Cardiologia e Fisiopatologia Cardiovascolare (P.V.) and Medicina Interna (G.S.), Angiologia e Malattie da Arteriosclerosi, University of Perugia, Perugia, Italy.

Correspondence to Francesco Perticone, MD, Department of Medicina Sperimentale e Clinica, Policlinico Mater Domini, Via Tommaso Campanella, 88100 Catanzaro, Italy. E-mail perticone{at}unicz.it

Background—— Forearm endothelial dysfunction, characterized by an impaired vasodilating response to acetylcholine (ACh), may be associated with several cardiovascular risk factors, including essential hypertension. Although the prognostic value of coronary endothelial dysfunction has been demonstrated, that of forearm endothelial dysfunction is still unknown.

Methods and Results—— Endothelium-dependent and -independent vasodilation was investigated in 225 never-treated hypertensive patients (age, 35 to 54 years) by intra-arterial infusion of increasing doses of ACh and sodium nitroprusside. Patients were divided into tertiles on the basis of their increase in ACh-stimulated forearm blood flow (FBF) from basal: group 1, from 30% to 184%; group 2, from 185% to 333%; and group 3, from 339% to 760% increase from basal. During a mean follow-up of 31.5 of months (range, 4 to 84 months), there were 29 major adverse events at the cardiac (n=19), cerebrovascular (n=9), or peripheral vascular (n=1) level. Events included myocardial infarction, angina, coronary revascularization procedures, stroke, transient cerebral ischemic attack, and aortoiliac occlusive disease. Event rate per 100 patient-years was 8.17, 4.34, and 2.02 in the first, second, and third tertiles of peak percent increase in FBF during ACh infusion. The excess risk associated with an FBF increase in the first tertile was significant (relative risk, 2.084; 95% CI, 1.25 to 3.48; P=0.0049) after controlling for individual risk markers, including 24-hour ambulatory blood pressure.

Conclusions—— Our data suggest that forearm endothelial dysfunction is a marker of future cardiovascular events in patients with essential hypertension.

Key Words: endothelium • cardiovascular diseases • hypertension

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				A. Natali, E. Toschi, S. Baldeweg, A. Casolaro, S. Baldi, A. M. Sironi, J. S. Yudkin, and E. Ferrannini Haematocrit, type 2 diabetes, and endothelium-dependent vasodilatation of resistance vessels Eur. Heart J., March 1, 2005; 26(5): 464 - 471. [Abstract] [Full Text] [PDF]

				R. K. Kharbanda, S. Wallace, B. Walton, A. Donald, J. M. Cross, and J. Deanfield Systemic Acyl-CoA:Cholesterol Acyltransferase Inhibition Reduces Inflammation and Improves Vascular Function in Hypercholesterolemia Circulation, February 15, 2005; 111(6): 804 - 807. [Abstract] [Full Text] [PDF]

				J. A Vita Polyphenols and cardiovascular disease: effects on endothelial and platelet function Am. J. Clinical Nutrition, January 1, 2005; 81(1): 292S - 297S. [Abstract] [Full Text] [PDF]

				D. Fischer, S. Rossa, U. Landmesser, S. Spiekermann, N. Engberding, B. Hornig, and H. Drexler Endothelial dysfunction in patients with chronic heart failure is independently associated with increased incidence of hospitalization, cardiac transplantation, or death Eur. Heart J., January 1, 2005; 26(1): 65 - 69. [Abstract] [Full Text] [PDF]

				U. Ghani, A. Shuaib, A. Salam, A. Nasir, U. Shuaib, T. Jeerakathil, F. Sher, F. O'Rourke, A. M. Nasser, B. Schwindt, et al. Endothelial Progenitor Cells During Cerebrovascular Disease Stroke, January 1, 2005; 36(1): 151 - 153. [Abstract] [Full Text] [PDF]

				M. P. C. Grooteman and M. J. Nube Impact of the type of dialyser on the clinical outcome in chronic haemodialysis patients: does it really matter? Nephrol. Dial. Transplant., December 1, 2004; 19(12): 2965 - 2970. [Full Text] [PDF]

				F. Wiesmann, S. E. Petersen, P. M. Leeson, J. M. Francis, M. D. Robson, Q. Wang, R. Choudhury, K. M. Channon, and S. Neubauer Global impairment of brachial, carotid, and aortic vascular function in young smokers: Direct quantification by high-resolution magnetic resonance imaging J. Am. Coll. Cardiol., November 16, 2004; 44(10): 2056 - 2064. [Abstract] [Full Text] [PDF]

				D. J Green, A. Maiorana, G. O'Driscoll, and R. Taylor Effect of exercise training on endothelium-derived nitric oxide function in humans J. Physiol., November 15, 2004; 561(1): 1 - 25. [Abstract] [Full Text] [PDF]

				S. Fazel, R. D. Weisel, and S. Verma A novel technique to assess flow-mediated vasodilation J. Am. Coll. Cardiol., October 6, 2004; 44(7): 1478 - 1480. [Full Text] [PDF]

				S. Fichtlscherer, S. Breuer, and A. M. Zeiher Prognostic Value of Systemic Endothelial Dysfunction in Patients With Acute Coronary Syndromes: Further Evidence for the Existence of the "Vulnerable" Patient Circulation, October 5, 2004; 110(14): 1926 - 1932. [Abstract] [Full Text] [PDF]

				C. Delles, M. P. Schneider, S. Oehmer, I. Fleischmann, E. F. Fleischmann, and R. E. Schmieder Increased response of renal perfusion to the antioxidant vitamin C in type 2 diabetes Nephrol. Dial. Transplant., October 1, 2004; 19(10): 2513 - 2518. [Abstract] [Full Text] [PDF]

				N. Gokce L-Arginine and Hypertension J. Nutr., October 1, 2004; 134(10): 2807S - 2811S. [Abstract] [Full Text] [PDF]

				T. Suvorava, N. Lauer, and G. Kojda Physical inactivity causes endothelial dysfunction in healthy young mice J. Am. Coll. Cardiol., September 15, 2004; 44(6): 1320 - 1327. [Abstract] [Full Text] [PDF]

				F. Perticone, R. Maio, G. Tripepi, and C. Zoccali Endothelial Dysfunction and Mild Renal Insufficiency in Essential Hypertension Circulation, August 17, 2004; 110(7): 821 - 825. [Abstract] [Full Text] [PDF]

				S R Johnson, P J Harvey, J S Floras, M Iwanochko, D Ibanez, D D Gladman, and M Urowitz Impaired brachial artery endothelium dependent flow mediated dilation in systemic lupus erythematosus: preliminary observations Lupus, August 1, 2004; 13(8): 590 - 593. [Abstract] [PDF]