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.