| Sung-Ji Park, Jeong-Rang Park, Su-nyoung Choi, Tae-Jung Kwon, So-La Park, Young-Ran Kang, Chung-Whan Gak, Jin-Young Hwang |
Background Endothelial dysfunction is an important early sign of atherosclerosis in hypercholesterolemic and hypertensive patients. The clinical benefits of statins therapy are well established. The aim of this study was to investigate antiatherosclerotic effect of statins compare with cholestyramine affecting plasma lipids. Methods In a randomized, double-blind, placebo-controlled trial, we studied 72 patients randomly assigned to receive pravastatin(40mg/d,27 patients,group P),cholestyramine resin(16g/d,23patients, group Q) or placebo(22patients,group C) during 2 months. To estimate the endothelial function, Flow-mediated dilatation(FMD) and nitroglycerin-induced, endothelium-independent vasodilatation(NMD) were measured in brachial artery using vascular ultrasound. As inflammatory markers, plasma WBC, ESR, IL-6 and hsCRP were measured before and after 2-month follow-up. Lymphocytes were isolated and Real-time RT-PCR(sense:5´-GCAAGATGTAGCCATGAAGTGC-3´, antisense:5´-CTTCTGCAAGAACCATCTGCC-3´) was done to estimate the expression of GRK2 in lymphocytes. Results Total cholesterol decreased in group P and Q, compared to the baseline by 17.1±14% and 17±10%(both P<0.001). LDL cholesterol decreased by 23.2±18% and 25.3±25%(both P<0.001). The mean reductions of total cholesterol(-17.1%, -17%) and LDL cholesterol(-23.2%, -25.3%) were observed in group P and Q. The hsCRP level in group P and Q(from 1.54±1.8 to 0.91±0.9mg/dl, from 1.99±2.3 to 0.59±0.38mg/dl: P<0.05) was dropped significantly. The levels of GRK2(C: from 0.061±0.023 to 0.075±0.031pg, P: from 0.024±0.02 to 0.015±0.01pg, Q: from 0.018±0.011 to 0.015±0.009pg, P=ns) were not altered significantly. FMD improved after therapy in group P and Q(from 5.5±4% to 8.9±3%, from 3.5±2% to 9.4±3%: P< 0.001), whereas NMD was not changed. Conclusions Endothelial function in hypercholesterolemic and hypertensive patients was improved by treatment with either pravastatin or cholestyramine. Atherogenic lipoprotein particles, LDL-cholesterol, elicit pro-inflammatory responses of cellular elements of the vessel wall, but not sympathetic regulation. This improvement is mediated by lowering of circulating LDL cholesterol.
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