阿托伐他汀改善高LDL-C相关血小板活化异常的临床研究

Atorvastatin inhibits enhanced platelet activation in patients with high LDL-C

目的探讨口服阿托伐他汀对高LDL-C血症相关的血小板异常活化功能的改善作用,阐明他汀类药物降低临床事件的新机制。方法从2012年11月至2013年7月于华山医院门诊就诊人群中,纳入LDL-C≥4.14mmol/L同时三酰甘油(triglycerides,TG)<1.7mmol/L且未经调脂治疗和抗血小板治疗者作为研究对象,作为阿托伐他汀治疗组(AT组),从体检中心招募健康志愿者作为对照组。测定血小板最大聚集率(maximal platelet aggregation,MPAG),全血流式细胞检测法测定血小板活化标志物CD62p(P-选择素)和PAC-1(GpⅡbⅢa)水平。对患者予以标准他汀治疗(阿托伐他汀20mg/天),并于治疗后1个月、2个月随访检测以上指标。结果 AT组共纳入40例,其中33例完成研究;对照组纳入并完成35例。两组人群基线资料(年龄、性别、BMI、吸烟史、血压、冠心病家族史、血糖)无明显差异;AT组患者服用阿托伐他汀治疗后,TC、TG、LDL-C均明显下降(P<0.05);基线时AT组血小板最大聚集率与对照组相似(33.03%±15.87%vs.29.05%±17.75%,P=0.102),采用他汀治疗2个月后,AT组患者血小板最大聚集率较基线显著下降但差异无统计学意义(P=0.073)。治疗前AT组CD62p和PAC-1均高于对照组(1.72±0.96 vs.0.90±0.77,P<0.001;4.33±2.42 vs.2.63±2.03,P<0.01);阿托伐他汀治疗2个月后,CD62p和PAC-1分别为0.85±0.72和1.50±1.07,与治疗前比较,两者表达均明显下降(P<0.05)。结论临床上阿托伐他汀可以改善高LDL-C相关的血小板活化。

Objective To discuss the relationships between high LDL-C level and the platetet activation, and to observe the effect of atorvastatin on the platelet activation of patients with high LDL- C level. Methods The eligible for this study were patients with LDL-C ≥ 4. 1 mmol/L and triglyeerides （TG）〈1. 7 mmol/I, and without lipid lowering therapy or antiplatelet therapy as threatment group （AT group）, and normocholesterolemic volunteers as control group. We used whole blood aggregometry and flow cytometry to monitor the levels of maximal platelet aggregation （MPAG） and platelet activation markers [CIX62p （P-seleetin） and PAC-1 （GP Ⅱb/Ⅲn）]. Furthermore, standard atorvastatin therapy （20 mg/d） was administrated by high level LDL-C patients, and the above assessments were obtained at the time points of baselinee and treatment for 1 and 2 months. Results In AT group,33 cases of 40 patients with high LDL-C level finished the study. All of 35 normoeholesterolemie volunteers in the control group finished the study. There was no significant difference between the two groups in age, sex, BM1, smoking history, blood pressure, family history of coronary artery disease, and fasting blood glucose. TC, TG and LDL-C decreased significanthly （P〈 0.05） in AT group after the treatment. MPAG was higher in AT group than that in control group,but without statistical difference （33.03 ± 15.87 vs. 29.05 ± 17.75 ,P = 0. 102） at baseline,and was lower than baseline after 2-month treatment without statistical difference （P = 0. 073）. The surface expression of platelet CD62p and PAC-1 were increased in AT group compared with control group with statistical difference （1.72± 0.96 vs. 0. 90 ± 0.77,P〈0. 001 and 4.33 ± 2.42 vs. 2.63 ±2.03,P〈 0.01）. By administrating atorvastatin for 2 months, the expression of platelet activation markers, CD62P and PAC-1 ,were reduced significantly in AT group （1.72 ± 0. 96 vs. 17.85 ± 0.72, P〈0. 001 and 4.33 ±2.42 vs. 1. 50± 1. 07,P〈0. 001 ）. Conclusions Atorvastatin improves the platelet hyper- activities induced by high level of LDL-C.