血小板活化标志物、维生素D与氯吡格雷抵抗的相关性

Relationship of Platelet Activation Markers and Vitamin D to Clopidogrel Resistance

目的探讨血小板活化标志物、维生素D与缺血性脑卒中患者抗血小板药物抵抗的相关性。方法 2017年6月至2018年6月,190例接受阿司匹林和氯吡格雷联合治疗的缺血性脑卒中患者,于用药后7～10 d检测二磷酸腺苷(ADP)和花生四烯酸(AA)诱导的最大血小板聚集率(MPAR)、血小板CD_(62p)活化百分率、血浆P选择素和维生素D。根据MPAR将患者分为抗血小板药物抵抗组和敏感组。结果阿司匹林抵抗率为1.2%,氯吡格雷抵抗率24.7%(抵抗组47例,敏感组143例)。抵抗组血小板CD_(62p)活化百分率(t=-5.232, P <0.001)、高血压患病率(χ~2=4.878, P <0.05)均高于敏感组,维生素D浓度明显低于敏感组(t=3.052, P <0.01),两组血浆P选择素浓度无显著性差异(t=-0.684, P=0.253)。Logistic回归分析结果显示,高血压(OR=5.538, 95%CI:1.204～25.470, P <0.05)、血小板CD62P活化百分率(OR=1.082,95%CI:1.041～1.092, P <0.05)是氯吡格雷抵抗的危险因素,而维生素D (OR=0.848, 95%CI:0.755～0.953,P <0.01)是氯吡格雷抵抗的保护因素。结论抑制血小板活化和补充维生素D可能有助于提高氯吡格雷的疗效。

Objective To explore the relationship of platelet activation markers and vitamin D to antiplatelet drug resistance in ischemic stroke patients.Methods From June,2017 to June,2018,190 patients with ischemic stroke were tested their maximum platelet aggregation rate(MPAR)induced by adenosine diphosphate(ADP)and arachidonic acid(AA),activation of platelet CD 62P and P-selectin vitamin D seven to ten days after dual antiplatelet treatment(aspirin 100 mg/d+clopidogrel 75 mg/d).According to the MPAR induced by ADP and AA,the patients were divided into resistance group and sensitive group.Results The prevalence of aspirin resistance was 1.2% ,while the prevalence of clopidogrel resistance was 24.7% (47 in the resistance group and 143 in the sensitive group).The activation of platelet CD62P(t=-5.232,P<0.001)and the prevalence of hypertension(χ^2=4.878,P<0.05)were more in the resistance group than in the sensitive group,while the vitamin D concentration was less(t=3.052,P<0.01).There was no significant difference in Pselectin between the resistance and sensitive groups(t=-0.684,P=0.253).Logistic regression analyses showed that hypertension(OR=5.538,95% CI:1.204-25.470,P<0.05),activation of platelet CD62P(OR=1.082,95% CI:1.041-1.092,P<0.05)and vitamin D(OR=0.848,95% CI:0.755-0.953,P<0.01)were the independent related factors for clopidogrel resistance.Conclusion Inhibition of platelet activation and supplementation of vitamin D may help to overcome the resistance of clopidogrel.