The Effect of Cholesterol Lowering Therapy on Endothelium-Dependent Vasodilation in Hypercholesterolemia

Kim, Woo Shik; Kim, Kwon Sam; Kim, Soo Joong; Kang, Heung Sun; Choue, Chung Whee; Song, Jung Sang; Bae, Jong Hoa

Abstract

BACKGROUND: Hypercholesterolemia is an important risk factor for cardiovascular disease, particulary ischemic heart disease, and it impairs endothelium-dependent vasodilation. Cholesterol-lowering therapy can improve cardiovascular morbidity and mortality in patients with atherosclerosis. Although the mechanism responsible are undear, it has been proposed that enhanced endothelial function might contribute to the improvement in clinical status. The purpose of this study was to examine brachial artery flow-mediated vasodilation(FMD) in patients with hypercholesterolemia and to determine if reduction of serum cholesterol with simvastatin, an inhibitor of HMG-CoA reductase, is associated with an improvement of endothelium-dependent vasodilation.
METHODS
Twenty one patients with hypercholesterolemia(mean+/-SD: age 59+/-7 yr) were studied. Endothelium-dependent, flow-mediated vasodilation and endothelium-independent nitroglycerin-mediated vasodilation(NMD) were assessed in the brachial artery using high resolution ultrasound 1) at baseline 2) during 12 weeks of simvastatin(10mg) therapy, and 3) after withdrawal of simvastatin for 4 weeks.
RESULTS
Simvastatin significantly decreased total cholesterol from 284+/-31 to 200+/-45mg/ dL, LDL-cholesterol from 178+/-39 to 115+/-44mg/dL, and triglyceride from 263+/-158 to 183+/-102mg/dL in 4 weeks after the drug administration(p=0.0005). At 12 weeks, total cholesterol, LDL-cholesterol and triglyceride fell to 201+/-36mg/dL, 104+/-46mg/dL and 219+/-215mg/dL. Flow mediated vasodilation rose from 6.1+/-4.1% at baseline to 9,7+/-6.4%(p<0.05), 11+/-4.3% and 12+/-3.5%(p=0.002) after 4, 8, 12 weeks therapy. But, after 4 weeks of simvastatin discontinuation(16 week), total cholesterol, LDL-cholesterol rose to 249+/-37mg/ dL, 115+/-44mg/dL(p=0.0002) and FMD fell to 4+/-5.7%(p(0.0002).
CONCLUSION
These findings suggest that cholesterol-lowering therapy with simvastatin leads to an improvement of FMD in the brachial artery of patients with hypercholesterolemia.