高剂量他汀对急性心肌梗死患者血小板功能及心室重构的影响

Effects of high dose atorvastatin administration on platelet activities and ventricular remodeling of patients with acute myocardial infarction

目的 评价负荷剂量联合高维持剂量阿托伐他汀治疗对急性ST段抬高心肌梗死（STEMI）患者血小板活化参数以及接受直接经皮冠状动脉介入（PCI）治疗后心室重构的影响与机制.方法 选择2012年6月至2013年12月在本院心内科住院并诊断为STEMI的患者260例,随机分为对照组（常规剂量组）140例及高剂量他汀组120例,检测患者直接PCI术前及术后平均血小板体积（MPV）、大血小板比例（P-LCR）、血小板活化指标CD62p、糖蛋白（Gp）Ⅱb/Ⅲa受体复合物（PAC-1）水平,记录直接PCI术后患者心肌灌注指标TIMI心肌灌注分级（TMPG）;患者于术后5～7d及出院6个月后行超声心动图测定左室舒张末期容积（LVEDV）、左室收缩末期容积（LVESV）、左室质量指数（LVMI）及左室射血分数（LVEF）.术后对患者随访6个月,动态追踪观察两组患者随访期内肝功能损害、肌病及心血管不良事件（MACE）的发生情况.结果 高剂量组患者术后MPV、P-LCR、CD62p 、PAC-1等血小板活化参数均低于对照组[（12.96±1.73）fl vs （14.18±1.86）fl,P＜0.05;（29.12±5.83）％ vs （30.66 ±6.12）％,P＜0.05;（45.36±5.24）％ vs （48.44±4.75）％,P＜0.01;（74.61±5.57）％ vs （78.55±5.78）％,P＜0.01],术后TMPG良好比例显著高于对照组（73.3％ vs 58.6％,P＜0.01）,出院6个月后,高剂量组患者LVEDV、LVESV、LVMI显著小于对照组,而LVEF则高于对照组[（110.46±8.86）ml vs（112.61±8.5）ml,P＜0.01;（60.16±6.13）ml vs（63.52±5.54）ml,P＜0.01;（101.69±4.35）g/m2 vs （103.96±4.17）g/m2,P＜0.05;（50.08±3.78）％ vs （48.47±4.12）％,P＜0.05],随访期间两组患者肝功能损害及肌病的发生情况差异无统计学意义（P＞0.05）,Kaplan-Meier生存分析显示高剂量组患者累积无MACE事件生存率显著高于对照组,Log rank检验差异有统计学意义（91.7％ vs 82.4％,Log rank =4.409,P=0.036）.结论 对STEMI患者应用高剂量他汀能显著降低患者血小板活化程度,改善直接PCI术后心肌灌注并减轻左心室重构,减少不良心血管事件的发生且具有良好的安全性.

Objective To investigate the effects of high dose atovastatin administration on platelet activity and ventricular remodeling of patients with ST-Segment elevation myocardial infarction （STEMI） underwent primary percutaneous coronary intervention （PCI）.Methods A total of 260 STEMI patients who hospitalized in our Department of Cardiology from June 2012 to December 2013 was enrolled and randomly divided into two groups：controlled group （n =140） and high dose atorvastatin group （n =120）.Indicators of platelet activities including mean platelet volume （MPV）,platelet large cell ratio （P-LCR）,blood CD62p,and glucose protein Ⅱ b/Ⅲa （PAC-1） were measured before and 48 hours after PCI.TIMI myocardial perfusion grade （TMPG） after PCI was recorded and patients accepted ultrasound cardiogram （UCG） examinations 5 ～7 days after PCI and 6 months after discharge.After PCI,Patients were followed up for 6 months,statin-associated liver impairment,myopath and major adverse cardiac events （MACE） happened during follow-up periods were recorded.Results MPV,P-LCR,CD62p,and PAC-1 in patients of high dose atorvastatin group were less than controlled group and TMPG were better than controlled group [（12.96±1.73）fl vs （14.18 ± 1.86）fl,P 〈0.05;（29.12 ±5.83）% vs （30.66 ±6.12）%,P 〈 0.05;（45.36±5.24）% vs （48.44±4.75）%,P 〈0.01;（74.61 ±5.57）% vs （78.55±5.78）%,P 〈0.01].Six months after PCI,UCG examination showed that Left ventricular end-diastolic volume （LV-EDV）,left ventricular end-systolic volume （LVESV） and left ventricular mass index （LVMI） in high dose group were less than controlled group while the left ventricular ejection fraction （LVEF） was higher than controlled group [（110.46 ±8.86）ml vs （112.61 ±8.5）ml,P 〈0.01;（60.16 ±6.13）ml vs （63.52 ± 5.54）ml,P 〈0.01;（1O1.69±4.35）g/m2 vs （103.96 ±4.17）g/m2,P 〈0.05;（50.08 ±3.78）% vs （48.47 ± 4.12） %,P 〈 0.05].After 6 months of follow-up,the incidence rate of statin-associated liver impairment and myopathe had no significant difference between two groups and Kaplan-Meier survival analysis showed patients of two groups had significantly different cumulative non-events survival rates （91.7% vs 82.4%,Log rank =4.409,P =O.036）.Conclusions Loading dose atorvastatin before PCI combined high maintenance dose after PCI can inhibit platelet activation and improve myocardial perfusion levels of patients with STEMI underwent primary PCI.It also can reduce Left ventricular remodeling and improve patient＇s prognosis without increasing side effects.