【摘要】 目的 观察冠状动脉粥样硬化性心脏病(冠心病)患者阿托伐他汀联合依折麦布降脂治疗过程中血清胆固醇合成与吸收标志物水平的动态变化。方法 收集2016年6—9月在首都医科大学附属北京安贞医院急诊科经冠状动脉造影证实的冠心病患者52例,给予阿托伐他汀20 mg/d口服治疗4周,根据危险分层治疗目标值判断血清总胆固醇、低密度脂蛋白胆固醇(LDL-C)是否达标继续分组治疗:血脂达标者入选单纯他汀组继续服用阿托伐他汀;血脂未达标者入选联合治疗组,阿托伐他汀联合依折麦布10 mg/d治疗,至8周结束。治疗前和治疗4、8周后以气相色谱法测定2组患者血清胆固醇合成标志物(7-烯胆甾烷醇和2,4-脱氢胆甾烷醇等)与吸收标志物(菜油固醇和谷固醇等)水平。结果 52例冠心病患者阿托伐他汀治疗4周后,血清总胆固醇和LDL-C水平均明显低于治疗前,差异有统计学意义[(3.91±0.11)mmol/L比(4.67±0.15)mmol/L、(2.20±0.09)mmol/L比(2.94±0.15)mmol/L](均P<0.05),总达标率为63.5%(33/52);联合治疗组治疗8周后血清总胆固醇和LDL-C水平较治疗4周后明显降低[(3.69±0.15)mmol/L比(4.41±0.13)mmol/L、(1.72±0.12)mmol/L比(2.78±0.14)mmol/L](均P<0.01),其中63.2%(12/19)患者达标;联合治疗组治疗前7-烯胆甾烷醇水平明显低于单纯他汀组[(11.0±2.5)mg/L比(17.2±3.5)mg/L](P<0.05);联合治疗组治疗8周后,菜油固醇、谷固醇及菜油固醇/总胆固醇比值均明显低于治疗4周后[(3.5±0.5)mg/L比(7.2±1.0)mg/L、(12.4±1.1)mg/L比(14.6±1.2)mg/L、(2.5±0.3)μg/mg比(4.3±0.5)μg/mg](均P<0.05)。结论 基线胆固醇高合成状态的冠心病患者可能通过降低胆固醇合成效率从阿托伐他汀治疗中获益;基线胆固醇低合成状态患者在他汀基础上联合依折麦布治疗可能通过降低胆固醇吸收效率使血脂达标率大幅度提高。更多还原

【Abstract】 Objective To observe changes of cholesterol absorption and synthesis markers in patients with coronary atherosclerotic heart disease(CHD) during lipid-lowing therapy with atorvastatin and ezetimibe.Methods Fifty-two patients with CHD diagnosed by coronary angiography from June to September 2016 in Beijing Anzhen Hospital,Capital Medical University were treated with atorvastatin 20 mg/d for 4 weeks.Patients with standard blood lipid level[total cholesterol(TC) and low density lipoprotein cholesterol(LDL-C)]after treatment were allocated to monotherapy group to continue atorvastatin;patients with abnormal blood lipid level were allocated to combined therapy group to take atorvastatin and ezetimibe(10 mg/d) for 4 weeks.Concentrations of cholesterol synthesis markers(lathosterol and desmosterol) and absorption markers(campesterol and sitosterol)were measured before and after 4,8 weeks of treatment by gas chromatography method.Results After 4 weeks of treatment with atorvastatin,levels of TC and LDL-C significantly decreased compared to those before treatment in52 cases[(3.91 ±0.11)mmol/L vs(4.67 ±0.15)mmol/L,(2.20 ±0.09)mmol/L vs(2.94 ±0.15)mmol/L](P < 0.05);the standard-reaching rate was 63.5%(33/52).After 8 weeks of treatment,levels of TC and LDL-C in combined therapy group(19 cases) were significantly lower than those 4 weeks before[(3.69 ±0.15)mmol/L vs(4.41 ±0.13)mmol/L,(1.72 ±0.12) mmol/L vs(2.78 ±0.14)mmol/L](P <0.01);the standard-reaching rate was 63.2%(12/19).The level of lathosterol in combined therapy group was significantly lower than that in monotherapy group before treatment[(11.0 ±2.5) mg/L vs(17.2 ± 3.5) mg/L](P < 0.05).Levels of campesterol,sitosterol and campesterol/TC ratio after 8 weeks of treatment in combined therapy group were significantly lower than those after 4 weeks of treatment[(3.5 ± 0.5) mg/L vs(7.2 ± 1.0) mg/L,(12.4 ±1.1)mg/L vs(14.6±1.2)mg/L,(2.5±0.3)(μg/mg vs(4.3 ±0.5) μg/mg](P <0.05).Conclusion CHD patients with high cholesterol synthesis level can benefit from atorvastatin through lowering cholesterol synthesis;patients with low cholesterol synthesis level should take ezetimibe in combination with atorvastatin to lower cholesterol absorption and blood lipid level.更多还原