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 e ffects of cholesterol-lowering therapy. Methods and 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 ar tery disease. Simvastatin lowered LDL-cholesterol by 40+/-12% from 130+/-28 mg/dL (P<0.001), Peak intracoronary acetylcholine infusion produced epicar dial coronary constriction at baseline in both the simvastatin (-17+/-13%) and placebo (-24+/-16%) groups. After treatment, acetylcholine produced les s constriction in both groups (-12+/-19% and -15+/-14%. respectively, P=0.9 7). 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 dilat ion of coronary microvessels. After treatment, the now 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 e ffect on coronary endothelial vasomotor function in the study population of patients with coronary artery disease and mildly elevated cholesterol leve ls. These findings suggest that the effects of cholesterol lowering on endo thelial function an more complex than previously thought.