Prognostic Significance of Endothelial Dysfunction in Hypertensive Patients

TLDR

Forearm endothelial dysfunction, defined by impaired acetylcholine‑induced vasodilation, is linked to cardiovascular risk factors such as essential hypertension, yet its prognostic value remains unclear compared to coronary endothelial dysfunction. The study assessed endothelium‑dependent and -independent vasodilation in 225 untreated hypertensive patients (age 35‑54) via intra‑arterial acetylcholine and sodium nitroprusside, categorizing them into tertiles based on the magnitude of forearm blood flow increase. During a mean 31.5‑month follow‑up, patients in the lowest tertile of forearm blood flow response experienced a significantly higher event rate (8.17 per 100 patient‑years, RR = 2.08) compared to higher tertiles, indicating that forearm endothelial dysfunction predicts future cardiovascular events in essential hypertension.

Abstract

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.