双抗患者缺血性脑卒中复发与血小板高反应性的相关性研究
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摘要
目的 探讨双联抗血小板治疗患者缺血性脑卒中复发与血小板高反应性及基因多态性的关系。方法 87例急性缺血性脑卒中患者被纳入,随访6个月,比较复发组和对照组血栓弹力图参数及CYP2C19基因多态性。结果 复发组2型糖尿病(69. 2%vs 37. 8%,χ~2=4. 46,P=0. 04)的发生比例较对照组高。复发组MA_(ADP)水平显著增高(52. 43±11. 80 vs 42. 17±26. 44,P=0. 02)、ADP%水平显著降低(22. 55±25. 60 vs 42. 17±26. 44,P=0. 01),两组MA_(AA)和AA%比较差异无统计学意义。MA_(ADP)的ROC曲线下面积为0. 749,47. 15是曲线临界点,此时灵敏度(84. 6%)和特异度(68. 9%)均较好。多因素Logistic回归模型显示MA_(ADP)与2型糖尿病(OR=1. 077,95%CI=1. 014～1. 144,P=0. 016; OR=3. 791,95%CI=1. 006～14. 285,P=0. 049)均为缺血性脑卒中复发的独立危险因素。结论 MA_(ADP)对缺血性脑卒中复发的诊断有意义,47. 15是MA_(ADP)预测复发的最佳临界值。MA_(ADP)和2型糖尿病是缺血性脑卒中复发的独立危险因素。
Objective To investigate the relationship between recurrence of ischemic cerebral infarction and high on-treatment platelet reactivity on dual antiplatelet treatment patients. Methods According to the 6 months follow-up,87 patients were divided into recurrent group and control group based on the recurrence of ischemic events. The parameters of thromboelastography and clopidogrel gene polymorphisms were compared. Results In the recurrent group,the incidence of diabetes( 69. 2% vs 37. 8%,χ~2= 4. 46,P = 0. 04) was higher. Compared with patients without ischemic events,MA_(ADP) was significantly higher and the ADP% was significantly lower in patients with ischemic events. There was no significant difference in MA_(AA)and AA% between two groups. From the ROC curve analysis,the area under the MA_(ADP)curve was0. 749,P = 0. 004,the area under the ADP% curve was 0. 284,P = 0. 013,indicating that both MA_(ADP)and ADP% made sense to the recurrent ischemic stroke diagnosis. 47. 15 was the cutoff point,and the sensitivity( 84. 6%) and specificity( 68. 9%) were both good. Logistic analysis identified MA_(ADP)and diabetes were independent risk factors for the recurrence of ischemic stroke with OR of 1. 077 and 3. 791. Conclusion MA_(ADP)was useful for the diagnosis of recurrent ischemic stroke,and 47. 15 was the cutoff point of the MA_(ADP). MA_(ADP)and diabetes were independent risk factors for the recurrence of ischemic stroke.
Objective To investigate the relationship between recurrence of ischemic cerebral infarction and high on-treatment platelet reactivity on dual antiplatelet treatment patients. Methods According to the 6 months follow-up,87 patients were divided into recurrent group and control group based on the recurrence of ischemic events. The parameters of thromboelastography and clopidogrel gene polymorphisms were compared. Results In the recurrent group,the incidence of diabetes( 69. 2% vs 37. 8%,χ~2= 4. 46,P = 0. 04) was higher. Compared with patients without ischemic events,MA_(ADP) was significantly higher and the ADP% was significantly lower in patients with ischemic events. There was no significant difference in MA_(AA)and AA% between two groups. From the ROC curve analysis,the area under the MA_(ADP)curve was0. 749,P = 0. 004,the area under the ADP% curve was 0. 284,P = 0. 013,indicating that both MA_(ADP)and ADP% made sense to the recurrent ischemic stroke diagnosis. 47. 15 was the cutoff point,and the sensitivity( 84. 6%) and specificity( 68. 9%) were both good. Logistic analysis identified MA_(ADP)and diabetes were independent risk factors for the recurrence of ischemic stroke with OR of 1. 077 and 3. 791. Conclusion MA_(ADP)was useful for the diagnosis of recurrent ischemic stroke,and 47. 15 was the cutoff point of the MA_(ADP). MA_(ADP)and diabetes were independent risk factors for the recurrence of ischemic stroke.
引文
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[4]中华医学会神经病学分会脑血管病学组缺血性脑卒中二级预防指南撰写组.中国缺血性脑卒中和短暂性脑缺血发作二级预防指南(2010)[J].中华神经科杂志,2015,48(4):68-74.
[5]Liu L,Gao YH,Cao J,et al.High prevalence of aspirin resistance in elderly patients with cardiovascular disease and metabolic syndrome[J].J Geriatr Cardiol,2016,13(6):531-536.
[6]Jia Q,Zhao X,Wang C,et al.Diabetes and poor outcomes within 6months after acute ischemic stroke:the China National Stroke Registry[J].Stroke,2011,42(10):2758-2762.
[7]Simpson SH,Abdelmoneim AS,Omran D,et al.Prevalence of high ontreatment platelet reactivity in diabetic patients treated with aspirin[J].Am J Med,2014,127(1):91-99.
[8]Aboonabi A,Singh I.The effectiveness of antioxidant therapy in aspirin resistance,diabetes population for prevention of thrombosis[J].Biomed Pharmacother,2016,83:277-282.
[9]蔡皓伟.急性缺血性脑卒中患者CYP2C19基因多态性与血小板抑制率的相关性分析[D].天津医科大学,2015.
[10]Patrono C,Andreotti F,Arnesen H,et al.Antiplatelet agents for the treatment and prevention of atherothrombosis[J].Eur Heart J,2011,32(23):2922-2932.
[11]Fiolaki A,Katsanos AH,Kyritsis AP,et al.High on treatment platelet reactivity to aspirin and clopidogrel in ischemic stroke:A systematic review and meta-analysis[J].J Neurol Sci,2017,376:112-116.
[12]Aradi D,Storey RF,Komocsi A,et al.Expert position paper on the role of platelet function testing in patients undergoing percutaneous coronary intervention[J].Eur Heart J,2014,35(4):209-215.
[13]Wang B,Li XQ,Ma N,et al.Association of thrombelastographic parameters with post-stenting ischemic events[J].J Neurointerv Surg,2017,9(2):192-195.
[14]Desta Z,Zhao X,Shin JG,et al.Clinical significance of the cytochrome P450 2C19 genetic polymorphism[J].Clin Pharmacokinet,2002,41(12):913-958.
[15]Kubica A,Kozinski M,Grzesk G,et al.Genetic determinants of platelet response to clopidogrel[J].J Thromb Thrombolysis,2011,32(4):459-466.
[16]Perry E.Clopidogrel hyporesponsiveness and the FDA boxed warning:detection and management of patients with genetic polymorphisms[J].Am J Health Syst Pharm,2011,68(6):529-532.
[17]Tang N,Yin S,Sun Z,et al.The relationship between on-clopidogrel platelet reactivity,genotype,and post-percutaneous coronary intervention outcomes in Chinese patients[J].Scand J Clin Lab Invest,2015,75(3):223-229.
[2]Gurbel PA,Bliden KP,Guyer K,et al.Platelet reactivity in patients and recurrent events post-stenting:results of the PREPARE POST-STENTING Study[J].J Am Coll Cardiol,2005,46(10):1820-1826.
[3]中华医学会神经病学分会.中国急性缺血性脑卒中诊治指南2014[J].中华神经科杂志,2015,48(4):246-257.
[4]中华医学会神经病学分会脑血管病学组缺血性脑卒中二级预防指南撰写组.中国缺血性脑卒中和短暂性脑缺血发作二级预防指南(2010)[J].中华神经科杂志,2015,48(4):68-74.
[5]Liu L,Gao YH,Cao J,et al.High prevalence of aspirin resistance in elderly patients with cardiovascular disease and metabolic syndrome[J].J Geriatr Cardiol,2016,13(6):531-536.
[6]Jia Q,Zhao X,Wang C,et al.Diabetes and poor outcomes within 6months after acute ischemic stroke:the China National Stroke Registry[J].Stroke,2011,42(10):2758-2762.
[7]Simpson SH,Abdelmoneim AS,Omran D,et al.Prevalence of high ontreatment platelet reactivity in diabetic patients treated with aspirin[J].Am J Med,2014,127(1):91-99.
[8]Aboonabi A,Singh I.The effectiveness of antioxidant therapy in aspirin resistance,diabetes population for prevention of thrombosis[J].Biomed Pharmacother,2016,83:277-282.
[9]蔡皓伟.急性缺血性脑卒中患者CYP2C19基因多态性与血小板抑制率的相关性分析[D].天津医科大学,2015.
[10]Patrono C,Andreotti F,Arnesen H,et al.Antiplatelet agents for the treatment and prevention of atherothrombosis[J].Eur Heart J,2011,32(23):2922-2932.
[11]Fiolaki A,Katsanos AH,Kyritsis AP,et al.High on treatment platelet reactivity to aspirin and clopidogrel in ischemic stroke:A systematic review and meta-analysis[J].J Neurol Sci,2017,376:112-116.
[12]Aradi D,Storey RF,Komocsi A,et al.Expert position paper on the role of platelet function testing in patients undergoing percutaneous coronary intervention[J].Eur Heart J,2014,35(4):209-215.
[13]Wang B,Li XQ,Ma N,et al.Association of thrombelastographic parameters with post-stenting ischemic events[J].J Neurointerv Surg,2017,9(2):192-195.
[14]Desta Z,Zhao X,Shin JG,et al.Clinical significance of the cytochrome P450 2C19 genetic polymorphism[J].Clin Pharmacokinet,2002,41(12):913-958.
[15]Kubica A,Kozinski M,Grzesk G,et al.Genetic determinants of platelet response to clopidogrel[J].J Thromb Thrombolysis,2011,32(4):459-466.
[16]Perry E.Clopidogrel hyporesponsiveness and the FDA boxed warning:detection and management of patients with genetic polymorphisms[J].Am J Health Syst Pharm,2011,68(6):529-532.
[17]Tang N,Yin S,Sun Z,et al.The relationship between on-clopidogrel platelet reactivity,genotype,and post-percutaneous coronary intervention outcomes in Chinese patients[J].Scand J Clin Lab Invest,2015,75(3):223-229.