Reduction in serum cholesterol with pravastatin improves endothelium-dependent coronary vasomotion in patients with hypercholesterolemia.

Abstract

BACKGROUND: This study aimed to determine if cholesterol-lowering therapy improves endothelium-dependent coronary vasomotion in patients with hypercholesterolemia. METHODS AND RESULTS: Nine patients with hypercholesterolemia were studied before and after cholesterol-lowering therapy with pravastatin (an inhibitor of HMG-CoA reductase) for 6 +/- 3 months, which lowered serum cholesterol from 272 +/- 8 to 187 +/- 16 mg/dL (P < .01). Control patients with serum cholesterol of 218 +/- 23 mg/dL also were studied twice in a similar interval (8 +/- 2 months) with no cholesterol-lowering drugs. Acetylcholine (the endothelium-dependent vasodilator) and papaverine and nitrate (endothelium-independent vasodilators) were infused into the study coronary artery. Changes in the diameter of the epicardial coronary artery and coronary blood flow were assessed by quantitative coronary arteriography and an intracoronary Doppler catheter. In patients with hypercholesterolemia, acetylcholine-induced vasoconstriction of the epicardial artery was less (P < .05) and the acetylcholine-induced increases in coronary blood flow were greater (P < .001) after than before pravastatin. In control patients, responses of the epicardial coronary artery and coronary blood flow to acetylcholine did not change over the follow-up period. The vasomotor responses to papaverine or nitrate were similar between the two groups, and no interval changes in their responses were noted in either group. CONCLUSIONS: These results suggest that cholesterol-lowering therapy with pravastatin may improve endothelium-dependent coronary vasomotion, which may possibly contribute to the improvement of myocardial perfusion as well as the regression of coronary atherosclerosis.