Effect of cholesterol-lowering therapy on coronary endothelial vasomotor function in patients with coronary artery disease.
BACKGROUND
Improved endothelial function may contribute to the beneficial effects of cholesterol-lowering therapy.


RESULTS
In this randomized, double-blind study, we compared the effect of 6 months of simvastatin (40 mg/d) treatment with that of placebo on coronary endothelial vasomotor function in 60 patients with coronary artery disease. Simvastatin lowered LDL-cholesterol by 40+/-12% from 130+/-28 mg/dL (P<0.001). Peak intracoronary acetylcholine infusion produced epicardial coronary constriction at baseline in both the simvastatin (-17+/-13%) and placebo (-24+/-16%) groups. After treatment, acetylcholine produced less constriction in both groups (-12+/-19% and -15+/-14%, respectively, P=0.97). The increase in coronary blood flow during infusion of the peak dose of substance P was blunted at baseline in both the simvastatin (42+/-50%) and placebo (55+/-71%) groups, reflecting impaired endothelium-dependent dilation of coronary microvessels. After treatment, the flow increase was 82+/-81% in the simvastatin group and 63+/-53% in the placebo group (P=0.16).


CONCLUSIONS
Six months of cholesterol-lowering therapy has no significant effect on coronary endothelial vasomotor function in the study population of patients with coronary artery disease and mildly elevated cholesterol levels. These findings suggest that the effects of cholesterol lowering on endothelial function are more complex than previously thought.
Vita
J A
JA
Boston University School of Medicine, Boston, MA, USA. jvita@bu.edu
Yeung
A C
AC
Winniford
M
M
Hodgson
J M
JM
Treasure
C B
CB
Klein
J L
JL
Werns
S
S
Kern
M
M
Plotkin
D
D
Shih
W J
WJ
Mitchel
Y
Y
Ganz
P
P
D000328:Adult; D000368:Aged; D000924:Anticholesteremic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002784:Cholesterol / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D003326:Coronary Circulation / Q000187:drug effects; D003327:Coronary Disease / Q000188:drug therapy* / Q000503:physiopathology; D003331:Coronary Vessels / Q000187:drug effects* / Q000503:physiopathology; D004311:Double-Blind Method; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000503:physiopathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010496:Pericardium / Q000187:drug effects / Q000503:physiopathology; D010919:Placebos; D019821:Simvastatin / Q000009:adverse effects / Q000627:therapeutic use*; D014666:Vasomotor System / Q000187:drug effects* / Q000503:physiopathology
D000924:Anticholesteremic Agents; D008078:Cholesterol, LDL; D010919:Placebos; D002784:Cholesterol; D019821:Simvastatin