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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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