Benefits of lipid lowering on vascular reactivity in patients with coronary artery disease and average cholesterol levels: A mechanism for reducing clinical events?

Background The favorable effects of lowering low-density lipoprotein (LDL)- cholesterol on reducing clinical events in patients with coronary disease h ave been well established. The mechanisms responsible for this benefit howe ver, have not been fully understood. This study examined the impact of lipi d-lowering therapy on endothelium-dependent vasoreactivity in a subgroup of patients after myocardial infarction with average cholesterol levels who p articipated in the Cholesterol Recurrent Events (CARE) study to determine w hether an effect on endothelial function is a viable mechanism for the obse rved reduction in clinical events. Methods and Results Participants were recruited from among volunteers in th e CARE trial at 2 university-based outpatient cardiology clinics. Patients were randomly assigned to pravastatin or placebo. Plasma lipids were measur ed at baseline and semiannually thereafter. During the final 6 months of th e trial, vasoreactivity was assessed by change in ultrasound-determined bra chial artery diameter in response to blood pressure cuff-induced ischemia ( endothelium-dependent) and to nitroglycerin, a direct vasodilator. Differen ces in response were examined between the 2 randomized groups. The relation between change in LDL-cholesterol from baseline to year 5 and the magnitud e of endothelium-dependent vasodilation also was examined. There was signif icantly greater endothelium-dependent vasodilation observed in the pravasta tin group compared with the placebo group (13% vs 8%, P = .0002), with no d ifference between the groups in their response to the endothelium-independe nt vasodilator nitroglycerin. The magnitude of the endothelium-dependent va sodilation was significantly correlated with the percent change in LDL-chol esterol from baseline to final visit (r = 0.49, P = .015). Conclusions These findings indicate that the use of pravastatin in patients after myocardial infarction with average cholesterol levels is associated with greater endothelium-dependent vasodilation compared with those who rec eived placebo. The magnitude of this vasodilatory response is correlated to the reduction in LDL-cholesterol. This improvement in endothelium-dependen t vasoreactivity may be a likely mechanism, at least in port, for the reduc tion in recurrent clinical events observed and reported in the CARE study.