Prognostic significance of endothelial dysfunction in hypertensive patients

Background-Forearm endothelial dysfunction, characterized by an impaired va sodilating 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 yea rs) by intra-arterial infusion of increasing doses of ACh and sodium nitrop russide. Patients were divided into tertiles on the basis of their increase in ACh-stimulated forearm blood flow (FBF) from basal: group 1, from 30% t o 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 mont hs), there were 29 major adverse events at the cardiac (n=19), cerebrovascu lar (n=9), or peripheral vascular (n=1) level. Events included myocardial i nfarction, 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 r isk associated with an FBF increase in the first tertile was significant (r elative 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 mark er of future cardiovascular events in patients with essential hypertension.