Elevated plasma fibrinogen and diabetes mellitus are associated with lower inhibition of platelet reactivity with clopidogrel
Elevated plasma fibrinogen and diabetes mellitus are associated with lower inhibition of platelet reactivity with clopidogrel
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DOI：
10.1016/j.jacc.2008.05.054
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发表时间：
2008-09-23
影响因子：
24
通讯作者：
Mahmud, Ehtisham
中科院分区：
文献类型：
--
作者：
Ang, Lawrence;Palakodeti, Vachaspathi;Mahmud, Ehtisham
目的本研究的目的是确定与心血管疾病（CVD）受试者中氯吡格雷的血小板抑制（PI）较低相关的因素。背景存在对氯吡格雷的异质性血小板反应，而氯吡格雷的次优PI的临床或生化预测因素尚不清楚。方法本研究前瞻性招募了需要氯吡格雷治疗的CVD受试者（招募前每日75 mg，持续≥ 7天或600 mg推注≥ 24 h）。床边快速血小板功能测定（VerifyNow，Acccumetrics，San Diego，加州）测量最大和氯吡格雷介导的血小板反应性，并鉴定与较低PI相关的因素。在157例受试者（年龄67.2 ± 12.2岁; 59.9%为男性）中观察到氯吡格雷的反应（平均40.8 ± 26.2%）。对已知影响血小板反应性的临床和生化因素进行多变量分析，发现血浆纤维蛋白原水平升高（>= 375 mg/dl）、糖尿病和体重指数（BMI）升高（>= 25 kg/m2）的患者PI较低。在相互作用测试中，纤维蛋白原水平升高与糖尿病状态相关，导致糖尿病患者PI较低（23.9 +/- 3.9% vs. 45.1 +/-4.5%，p < 0.001），但非糖尿病患者无此现象（44.7 +/- 4.4% vs. 46.3 +/-4.8%，p = 0.244）。无论糖尿病状态或纤维蛋白原水平如何，氯吡格雷治疗后BMI增加与PI降低独立相关（36.8 +/- 9.0% vs. 49.0 +/-7.0%，P < 0.001）。在有糖尿病和BMI增加（>= 25 kg/m2）的CVD患者中，氯吡格雷的PI较低。
Objectives The goal of this study was to identify factors associated with lower platelet inhibition ( PI) with clopidogrel in subjects with cardiovascular disease (CVD).Background A heterogeneous platelet reactivity response to clopidogrel exists, and the clinical or biochemical predictors of suboptimal PI with clopidogrel remain unclear.Methods This study prospectively enrolled subjects with CVD requiring treatment with clopidogrel (75 mg daily for >= 7 days or 600-mg bolus >= 24 h before recruitment). A bedside rapid platelet function assay (VerifyNow, Acccumetrics, San Diego, California) to measure maximal and clopidogrel-mediated platelet reactivity was utilized, and factors associated with lower PI were identified.Results A heterogeneous, normally distributed PI (mean 40.8 +/- 26.2%) response to clopidogrel was observed in 157 subjects (age 67.2 +/- 12.2 years; 59.9% men). Multiple variable analysis of clinical and biochemical factors known to affect platelet reactivity revealed lower PI in patients with an elevated plasma fibrinogen level (>= 375 mg/dl), diabetes mellitus, and increased body mass index (BMI) (>= 25 kg/m(2)). On testing for interaction, elevated fibrinogen level was associated with diabetic status, resulting in lower PI in diabetic patients (23.9 +/- 3.9% vs. 45.1 +/- 4.5%, p < 0.001), but not nondiabetic patients (44.7 +/- 4.4% vs. 46.3 +/- 4.8%, p = 0.244). Increased BMI remained independently associated with lower PI after clopidogrel therapy regardless of diabetic status or fibrinogen level (36.8 +/- 9.0% vs. 49.0 +/- 7.0%, p < 0.001).Conclusions Elevated plasma fibrinogen (>= 375 mg/dl) in the presence of diabetes mellitus and increased BMI (>= 25 kg/m(2)) are associated with lower PI with clopidogrel in patients with CVD.