停用辛伐他汀对健康男性肱动脉内皮功能的影响

The effects of simvastatin withdrawal on brachial artery endothelial function in healthy normocholesterolemic men

目的观察停用辛伐他汀对TC水平正常健康男性肱动脉内皮功能的影响。方法16例健康青年男性服用20mg辛伐他汀4周后停药，分别检测停药前后不同时间点肱动脉内皮依赖性舒张功能（FMD），并测定血管活性物质——NO、血浆内皮素和6-酮．前列腺素F1α（6-keto-PGF1α）以及血脂参数的变化。结果健康男性服用辛伐他汀4周后，在停药第1天观察到FMD较停药前明显降低，甚至低于未服药时的基线水平（P〈0．05）。停药后血清NO水平较停药前和基础值亦明显降低，其变化与FMD的变化一致。停药后血浆内皮素水平升高，6-keto-PGF1α水平降低。血清LDL-C在停药后最初2d内无明显改变，其变化与FMD无明显相关。结论健康男性服用辛伐他汀后突然停药，不仅使该药对肱动脉内皮功能的改善作用迅速消失，而且还对血管内皮功能造成进一步损害，该不良影响可能与循环中NO水平降低有关，是非TC依赖性的。

Objective To determine whether acute withdrawal of simvastatin treatment in healthy normocholesterolemic men impairs the brachial artery endothelial function. Methods The study was performed on 16 healthy, young male subjects with desirable serum levels of cholesterol. They were administered with simvastatin （20 mg/d） for 4 weeks. Endothelial dependent flow-mediated vasodilation （FMD） was assessed on the brachial artery using high-resolution ultrasound, and fasting serum lipid profiles as well as vasoactive substances [ NO, endothelin （ET） and 6-keto-PGF1α] were measured. The parameters mentioned above were obtained at indicated time points before and after simvastatin treatment. Results Simvastatin treatment for 4 weeks significantly improved FMD and reduced low density LDL-C and total TC levels. Withdrawal of simvastatin, however, resulted in dramatic impairment of endotheliumdependent relaxation on the first day after with drawal [ （4. 6 ± 0.48 ） % and （ 10.9 ± 0. 89） %, P 〈 0.01 ], Furthermore, FMD decreased significantly as compared with baseline level [ （4.6 ± 0. 48 ） % vs （ 6. 4 ± 0.47 ）%, P 〈0.01 ]. Serum NO level varied according to the change of endothelial-dependent relaxation （γ= 0. 496,P 〈 0. 01 ）. After discontinuing simvastatin therapy, plasma ET increased and plasma 6-keto- PGF1α decreased progressively. In addition, serum TC and LDL-C were not significantly modified during the initial 2 days. No correlation was shown between FMD and serum LDL-C level （γ= -0. 172,P =0. 101 ）. Conclusions Withdrawal of simvastatin not only abrogates the beneficial effect on endothelial function of healthy normocholesterolemic men rapidly, but also induces further endothelial deterioration as compared with pretreatment status. This adverse effect is independent of serum cholesterol. The underlying mechanism may be related to the suppression of endothelial NO production.