Beneficial effect of cholesterol-lowering therapy on coronary endothelium-dependent relaxation in hypercholesterolaemic patients

Abstract

Since hypercholesterolaemia is associated with impaired endothelium-dependent vasodilation, a study was conducted to find out whether cholesterol reduction will improve endothelial function in patients with hypercholesterolaemia and normal coronary arteries.25 men (mean age 51 [SD 8] years) with total serum cholesterol >6·2 mmol/L) and angiographically normal coronary arteries had their coronary vasomotor responses to intracoronary acetylcholine and nitroglycerin assessed by computer-assisted quantitative angiography at baseline and after 6 months of cholesterol-reducing diet and cholestyramine. Between baseline and follow-up mean total serum cholesterol level fell by 28·7 (SD 5·6)% (p <0·001); mean low-density lipoprotein (LDL) cholesterol level by 35·6 (8·7)% (p <0·001); and mean total cholesterol to high-density lipoprotein (HDL) cholesterol ratio by 29·4 (10·6)% (p <0·001). Acetylcholine significantly reduced the mean segment diameter at baseline, by 21·7 (14·0)% (p <0·01), but it increased the diameter at follow-up, by 6·16 (13·3)% (p <0·01), the difference between the two occasions being significant (p < 0·001). Nitroglycerin significantly increased the mean segment diameter, both at baseline, by 18·7 (11·5)% (p <0·01), and at follow-up, by 19·3 (12·1)% (p <0·01), the difference between the two responses being not significant. At baseline total cholesterol and LDL cholesterol did not correlate with acetylcholine response, but they did at follow-up (total cholesterol, r = 0·67, p <0·01; LDL cholesterol, r = 0·64, p <0·01).Impairment of endothelium-dependent (acetylcholine-induced) dilation of the epicardial coronary arteries in hypercholesterolaemic patients with angiographically normal coronary arteries is thus reversible by reducing serum cholesterol. In addition, the degree of impairment of acetylcholine-induced vasomotor response is related to the cholesterol concentrations after therapy.