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

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.