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 have been well established. The mechanisms responsible for this benefit however, have not been fully understood. This study examined the impact of lipid-lowering therapy on endothelium-dependent vasoreactivity in a subgroup of patients after myocardial infarction with average cholesterol levels who participated in the Cholesterol Recurrent Events (CARE) study to determine whether an effect on endothelial function is a viable mechanism for the observed reduction in clinical events. Methods and Results Participants were recruited from among volunteers in the CARE trial at 2 university-based outpatient cardiology clinics. Patients were randomly assigned to pravastatin or placebo. Plasma lipids were measured at baseline and semiannually thereafter. During the final 6 months of the trial, vasoreactivity was assessed by change in ultrasound-determined brachial artery diameter in response to blood pressure cuff-induced ischemia (endothelium-dependent) and to nitroglycerin, a direct vasodilator. Differences in response were examined between the 2 randomized groups. The relation between change in LDL-cholesterol from baseline to year 5 and the magnitude of endothelium-dependent vasodilation also was examined. There was significantly greater endothelium-dependent vasodilation observed in the pravastatin group compared with the placebo group (13% vs 8%, P = .0002), with no difference between the groups in their response to the endothelium-independent vasodilator nitroglycerin. The magnitude of the endothelium-dependent vasodilation was significantly correlated with the percent change in LDL-cholesterol 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 received placebo. The magnitude of this vasodilatory response is correlated to the reduction in LDL-cholesterol. This improvement in endothelium-dependent vasoreactivity may be a likely mechanism, at least in port, for the reduction in recurrent clinical events observed and reported in the CARE study.