Cervera A, Tàssies D, Obach V, Amaro S, Reverter J C, Chamorro A
Stroke Unit, Department of Neurological Sciences, Hospital Clinic, University of Barcelona, and Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain.
Cerebrovasc Dis. 2007;24(2-3):242-6. doi: 10.1159/000104485. Epub 2007 Jun 28.
The contribution of genetic factors to aspirin treatment failure (ATF) for secondary prevention is not settled in patients with ischemic stroke.
We assessed the polymorphisms VNTR (A, B, C, D) of glycoprotein (GP) Ibalpha, 807C/T of GP Ia/IIa, and Pl(A1/A2) of GP IIb/IIIa, and the 5-year incidence of major recurrent events in 82 stroke patients with no major sources of cardioembolism (mean age 70, SD 9.0 years; female gender 23%). Using a structured interview, all participants confirmed good compliance with aspirin (100-300 mg/day) for secondary prevention. Demographics and atherothrombotic risk factors assessed included diabetes, hypertension, dyslipemia, smoking, and coronary heart disease.
Thirty-one stroke patients had one recurrent stroke or myocardial infarction within 33 (7-48) months of aspirin onset, while 51 patients demonstrated an uneventful clinical course. Female gender (p < 0.05), diabetes (p < 0.05), dyslipemia (p < 0.05), and the BC genotype of VNTR (25.8 vs. 7.8%, p < 0.05) were more prevalent in patients in whom aspirin failed to prevent clinical events than in those in whom it did not. The BC genotype of VNTR was the only factor that remained associated with ATF in an age-, sex-, and risk factor-adjusted logistic regression analysis (OR 9.6, 95% CI 1.5-61.0).
The BC genotype of the VNTR polymorphism of GP Ibalpha is an independent predictor of recurrent events in stroke patients treated with aspirin. This finding suggests that high shear-induced platelet activation mediated by GP Ibalpha and von Willebrand factor is an important contributor to ATF in the stroke population.
在缺血性中风患者中，遗传因素对阿司匹林二级预防治疗失败（ATF）的影响尚未明确。
我们评估了糖蛋白（GP）Ibalpha的VNTR（A、B、C、D）多态性、GP Ia/IIa的807C/T以及GP IIb/IIIa的Pl（A1/A2），并评估了82例无主要心源性栓塞来源的中风患者（平均年龄70岁，标准差9.0岁；女性占23%）5年内主要复发事件的发生率。通过结构化访谈，所有参与者均确认在二级预防中对阿司匹林（100 - 300毫克/天）的依从性良好。评估的人口统计学和动脉粥样硬化血栓形成危险因素包括糖尿病、高血压、血脂异常、吸烟和冠心病。
31例中风患者在阿司匹林治疗开始后的33（7 - 48）个月内发生了一次复发性中风或心肌梗死，而51例患者临床过程平稳。与阿司匹林成功预防临床事件的患者相比，女性（p < 0.05）、糖尿病（p < 0.05）、血脂异常（p < 0.05）以及VNTR的BC基因型（25.8%对7.8%，p < 0.05）在阿司匹林未能预防临床事件的患者中更为普遍。在年龄、性别和危险因素调整的逻辑回归分析中，VNTR的BC基因型是唯一与ATF相关的因素（比值比9.6，95%置信区间1.5 - 61.0）。
GP Ibalpha的VNTR多态性的BC基因型是接受阿司匹林治疗的中风患者复发事件的独立预测因子。这一发现表明，由GP Ibalpha和血管性血友病因子介导的高剪切力诱导的血小板活化是中风人群中ATF的重要促成因素。
