停用阿托伐他汀对健康男性血管内皮功能的影响

Effects of Atorvastatin discontinuation on vascular endothelial function in health young men

目的观察停用阿托伐他汀对血脂水平正常的健康男性青年肱动脉内皮功能的影响。方法30例健康男性青年每日服用20mg阿托伐他汀28d后停药,以高分辨率超声测定的肱动脉血流介导内皮依赖性舒张功能(FMD)作为内皮功能的评价指标,分别检测用药前、停药前、停药后1、3、7d肱动脉FMD、一氧化氮(NO)、血浆内皮素(ET)以及血脂参数的变化。结果停药第1天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ET-I水平升高,血清LDL-C在停药后最初3d内无明显改变,其变化与FMD无明显相关性。结论停用阿托伐他汀,不仅使其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损害,该不良影响可能与循环中NO水平下降有关。提示他汀类药物不能轻易停用。

[Objective] To observe the effect of Atorvastatin discontinuation on brachial artery endothelial function with health young male subjects. [Methods] 30 health young male volunteers were given Atorvastatin （20 mg/d） for 28 days. Before treatment, withdrawal and after treatment 1, 3, 7 days, endothelium-dependent flow-mediated vasodilation （FMD） was assessed on the brachial artery using high-resolution ultrasound. The plasma levels of nitric oxide （NO）, endothelial-1 （ET-1） and lipid were detected. [Results] After 28 days treatment of Atorvastatin, FMD was significantly improved and the plasma low density lipoprotein （LDL-C）, triglyeeride （TG） and total cholesterol （TC） were reduced. Discontinuation of Atorvastatin, however, resulted in dramatic impairment of endothelium-depen- dent relaxation on the first day after withdrawal （P 〈0.01）. Furthermore, FMD decreased significantly as compared with baseline level （P 〈0.01）. Serum NO level varied according to the change of endothelial-dependent relaxation （P 〈0.01）. After treatment of Atorvastatin, plasma ET-I increased. Serum TG and LDL-C were not significantly modi- fied during the initial 3 days. No correlation was shown between FMD and serum LDL-C level （P 〉0.05）. [Con- clusions] Withdrawal of Atorvastatin not only loses the beneficial effect on the brachial artery endothelial function of health young men rapidly, but also causes further endothelial damage as compared with that of pretreatment. The underlying mechanism may be related to the suppression of endothelial NO production. It suggests that statins drugs should not be withdrawn.