停用辛伐他汀对冠心病及冠心病危险因素患者血管内皮功能的影响  

The effects after withdrawal of simvastatin on brachial artery endothelial function in patient with coronary heart disease or risk factors

作　　者：陈红[1] 任景怡[1] 武蓓[1] 刘昕[1] 汪若婕[1] 李丽君[1] 罗宇[1] 

机构地区：[1]北京大学人民医院心内科,100044

出　　处：《中华心血管病杂志》2007年第6期531-535,共5页Chinese Journal of Cardiology

基　　金：国家自然科学基金(30240036)

摘　　要：目的观察在冠心病及冠心病危险因素患者中,停用辛伐他汀治疗对血管内皮功能的影响,并探讨相应作用机制。方法入选33例血清胆固醇(TC)水平未达标的冠心病及冠心病危险因素患者,分别于基线水平、停药前(即辛伐他汀20 mg 治疗4周后)及停用辛伐他汀1周时,采用高分辨超声技术检测肱动脉血流介导性扩张(FMD)评估血管内皮依赖性舒张功能,并测定一氧化氮(NO)、血浆内皮素(ET)、6-酮-前列腺素 F1_α(6-keto-PGF1_α)和血栓素 B_2(TXB_2)的水平及主要血脂参数的变化。结果辛伐他汀治疗4周后可有效降低冠心病及冠心病危险因素患者 TC、低密度脂蛋白胆固醇(LDL-C)水平,并明显改善患者肱动脉内皮依赖性舒张功能(FMD)。然而,停用辛伐他汀治疗1周后,所有患者肱动脉内皮依赖性舒张功能均较停药前明显下降(4.82±0.71)%与11.51±0.87%,P<0.01),甚至低于未服用辛伐他汀时的基线水平(4.82±0.71%与5.89±0.65%,P<0.01),其中冠心病患者停药后 FMD 下降幅度较仅有冠心病危险因素患者更显著(65.6%与56.3%,P<0.01)。停药1周后,患者血清 NO 水平较停药前及基础值均明显降低,而血浆 ET 水平升高。血浆 TXB_2水平在停药前后无明显变化。此外,停药后患者血清 LDL-C 水平虽较治疗4周时有所升高,但仍未恢复至基线水平。停药后肱动脉 FMD 的变化仅与血清 NO 降低幅度呈正相关关系(r=0.674,P=0.004),而与血清 LDL-C 水平变化无明显相关性(r=-0.414,P=0.083)。结论在 TC水平未达标的冠心病及冠心病危险因素患者中突然终止辛伐他汀治疗可在1周内完全逆转该药对血管内皮功能的改善作用,甚至还可能导致血管内皮功能进一步恶化。并且这种撤药反应随基础疾病的严重性增加。停药所致血管内皮功能损害可能与血管内皮源性的 NO 减少有关,是非胆固醇依赖性作用。Objective Landmark trials have demonstrated that statins can reduce the risk of coronary events. Despite the widespread use of statins in the settings of primary and secondary prevention of CHD, withdrawal of statins is a frequent problem in clinical practice. Several recent clinical studies have suggested that withdrawal of statin therapy might be associated with an increase in thrombotic vascular events and the onset of acute coronary syndromes. However, the effects of discontinuing of statins treatment on endothelial function and underlying mechanism are unknown. Objectives We investigated the effects after withdrawal of simvastatin on brachial artery endothelial function in patients unreached cholesterol target with coronary heart disease （CHD） or CHD risk factors. Methods We included 33 patients with established CHD or CHD risk factors, whose serum cholesterol did not achieve NCEP target level. They were administered simvastatin （20 mg） for 4 weeks. Endothelial dependent flow-mediated vasodilation （FMD） was assessed in the brachial artery using high-resolution ultrasound at baseline, after 4 weeks of simvastatin and after termination of therapy 1 week. We evaluated fasting serum lipid profiles and vasoactive substances simultaneously, included nitric oxide （NO）, endothelin （ET）, 6-keto-PGF1α and thromboxane B2 （TXB2 ）, which were measured as plasma prostacyclin and TXA2 respectively. Results Simvastatin treatment reduced low density lipoprotein cholesterol （LDL-C） and total cholesterol （TC） levels and improved endothelial-dependent vasodilation in patients after 4 weeks. Withdrawal of simvastatin, however, FMD showed a significant reduction [ （4. 82 ± 0. 71 ） % vs （ 11.51 ± 0. 87 ） % , P 〈 0.01 ], that remained in low level after 1 week, and the FMD were even lower than the baseline values[ （4. 82 ±0. 71 ） % vs （5. 89 ± 0. 65） % ,P 〈 0.01 ]. After terminating simvastatin treatment, serum NO and plasma 6-keto-PGFl,, levels decreased, as well as plasma E

关 键 词：冠状动脉疾病 降血脂药 内皮 血管 

分 类 号：R541.4[医药卫生—心血管疾病]