Prognostic significance of endothelial dysfunction in hypertensive patients.
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.
Perticone
F
F
Internal Medicine and Cardiovascular Diseases Unit, Department of Medicina Sperimentale e Clinica "G. Salvatore," University of Catanzaro Magna Graecia, Catanzaro, Italy. perticone@unicz.it
Ceravolo
R
R
Pujia
A
A
Ventura
G
G
Iacopino
S
S
Scozzafava
A
A
Ferraro
A
A
Chello
M
M
Mastroroberto
P
P
Verdecchia
P
P
Schillaci
G
G
D000109:Acetylcholine / Q000008:administration & dosage; D000328:Adult; D000959:Antihypertensive Agents / Q000627:therapeutic use; D001783:Blood Flow Velocity / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D018450:Disease Progression; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology*; D005260:Female; D005500:Follow-Up Studies; D005542:Forearm / Q000098:blood supply / Q000503:physiopathology; D006801:Humans; D006973:Hypertension / Q000175:diagnosis* / Q000188:drug therapy / Q000503:physiopathology*; D007261:Infusions, Intra-Arterial; D008297:Male; D008875:Middle Aged; D009599:Nitroprusside / Q000008:administration & dosage; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000008:administration & dosage
D000959:Antihypertensive Agents; D014665:Vasodilator Agents; D009599:Nitroprusside; D000109:Acetylcholine