Endothelium-dependent responses in patients with hypercholesterolemic coronary artery disease under the effects of simvastatin and enalapril, either separately or combined.
BACKGROUND
Endothelial dysfunction is an early event in atherosclerotic disease that precedes clinical manifestations and complications. The noninvasive assessment of endothelial function in patients with risk factors undergoing clinical treatment is an important medical advance. In this setting, altered endothelial function in patients with coronary hypercholesterolemia and its modifications by treatment with enalapril and simvastatin, either separately or in combination, was assessed in the brachial artery in a randomized, double-blind, 2-period crossover study.


METHODS
Thirty-eight patients were separated in 2 groups. Group 1 (18 patients, 3 female, mean age 63 +/- 6.0 years) received simvastatin 10 mg/d for 8 weeks and simvastatin plus enalapril 5 mg/d for another 8 weeks. Group 2 (20 patients, 3 female, mean age 64 +/- 5.8 years) received enalapril 5 mg/d for 8 weeks and enalapril plus simvastatin 10 mg/d for another 8 weeks. All subjects underwent measurements of brachial artery diameter before and after postischemic hyperemia with high-resolution ultrasound at basal conditions (control) and under the effects of the drugs at the end of 8 and 16 weeks.


RESULTS
Cholesterol and LDL cholesterol levels significantly decreased with simvastatin treatment alone or with enalapril. Mean baseline arterial diameter was 5.24 +/- 1.25 mm in group 1 and 4.83 +/- 0.99 mm in group 2 (not significant). In group 1 after the first 8 weeks, endothelium-dependent vasodilation significantly increased with simvastatin treatment (control, 4.4%; 8 weeks, 7.6%; P <.001). After 16 weeks with the addition of enalapril, a further increase in vasodilation was seen (8.6%, P <.05 vs 8 weeks). In group 2, with enalapril treatment an increase in vasodilation versus control was seen (control, 4.3%; 8 weeks, 5.8%; P <.01). After 16 weeks, with the addition of simvastatin an additional increase in vasodilation was observed (9.1%, P <.001 vs 8 weeks). After nitroglycerin, vasodilation in group 1 at control, 8, and 16 weeks was 17%, 17.5%, and 18%, respectively. In group 2, nitroglycerin vasodilation at control, 8, and 16 weeks was 21%, 21%, and 22%, respectively.


CONCLUSIONS
Simvastatin significantly increased the postischemic vasodilator response in patients with coronary hypercholesterolemia, either as single treatment or added to enalapril. Similarly, the response was increased by enalapril, either alone or while simvastatin was being administered. Both drugs improve vasodilation and additive effects appear to be present.
Esper
R J
RJ
Department of Medicine, University of Buenos Aires, Argentina. ricardo.esper@mundomail.net
Machado
R
R
Vilariño
J
J
Cacharrón
J L
JL
Ingino
C A
CA
García Guiñazú
C A
CA
Bereziuk
E
E
Bolaño
A L
AL
Suarez
D H
DH
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D001916:Brachial Artery / Q000000981:diagnostic imaging / Q000187:drug effects / Q000503:physiopathology; D002784:Cholesterol / Q000097:blood; D003327:Coronary Disease / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D004656:Enalapril / Q000627:therapeutic use*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology*; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D006937:Hypercholesterolemia / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D019821:Simvastatin / Q000627:therapeutic use*; D014463:Ultrasonography; D014664:Vasodilation / Q000187:drug effects
D000806:Angiotensin-Converting Enzyme Inhibitors; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D004656:Enalapril; D002784:Cholesterol; D019821:Simvastatin