Influence of Sex on Platelet Reactivity in Response to Aspirin.
Influence of Sex on Platelet Reactivity in Response to Aspirin.
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DOI：
10.1161/jaha.119.014726
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发表时间：
2020-07-21
影响因子：
5.4
通讯作者：
Voora D
中科院分区：
文献类型：
--
作者：
Friede KA;Infeld MM;Tan RS;Knickerbocker HJ;Myers RA;Dubois LG;Thompson JW;Kaddurah-Daouk R;Ginsburg GS;Ortel TL;Voora D
阿司匹林预防心肌梗塞和中风的有效性和安全性存在性别差异。这是否可以通过血小板反应性和阿司匹林反应的潜在差异来解释，目前还知之甚少。健康志愿者(n=378 ，208例)和有冠状动脉疾病或冠状动脉疾病危险因素的患者(n=217， ，112例)服用阿司匹林，疗程为4周。使用富含血小板血浆的透光性聚集法在基线、第一次服用阿司匹林后3小时和每日服用阿司匹林4周后测量血小板对肾上腺素、胶原和ADP的反应性。对一组患者进行了药代动力学和药效学评估，包括水杨酸盐和环氧合酶-1衍生的前列腺素代谢物水平，以及对花生四烯酸的反应和体外暴露于阿司匹林后的透光率聚集法。在基线时，女性对ADP和胶原蛋白的反应是增加了血小板聚集性。阿司匹林对先天血小板的反应，通过体外阿司匹林暴露于基线血小板来评估，没有性别差异。在第一次口服阿司匹林三小时后，肾上腺素对女性的血小板聚集有更大程度的抑制，胶原蛋白对其抑制程度较小。在每日治疗4周后，尽管水杨酸盐浓度较高，环氧合酶-1抑制作用更强，但女性对肾上腺素和ADP的血小板抑制作用有所减弱。我们观察了阿司匹林对血小板反应中激动剂依赖性的性别差异。尽管环氧合酶-1抑制作用更强，但随着时间的推移，每天服用阿司匹林导致女性对肾上腺素和ADP反应的血小板抑制反常地减弱，但在男性中没有。
There are sex differences in the efficacy and safety of aspirin for the prevention of myocardial infarction and stroke. Whether this is explained by underlying differences in platelet reactivity and aspirin response remains poorly understood. Healthy volunteers (n=378 208 women) and patients with coronary artery disease or coronary artery disease risk factors (n=217 112 women) took aspirin for 4 weeks. Light transmittance aggregometry using platelet‐rich plasma was used to measure platelet reactivity in response to epinephrine, collagen, and ADP at baseline, 3 hours after the first aspirin dose, and after 4 weeks of daily aspirin therapy. A subset of patients underwent pharmacokinetic and pharmacodynamic assessment with levels of salicylate and cyclooxygenase‐1–derived prostaglandin metabolites and light transmittance aggregometry in response to arachidonic acid and after ex vivo exposure to aspirin. At baseline, women had increased platelet aggregation in response to ADP and collagen. Innate platelet response to aspirin, assessed with ex vivo aspirin exposure of baseline platelets, did not differ by sex. Three hours after the first oral aspirin dose, platelet aggregation was inhibited in women to a greater degree in response to epinephrine and to a lesser degree with collagen. After 4 weeks of daily therapy, despite higher salicylate concentrations and greater cyclooxygenase‐1 inhibition, women exhibited an attenuation of platelet inhibition in response to epinephrine and ADP. We observed agonist‐dependent sex differences in platelet responses to aspirin. Despite higher cyclooxygenase‐1 inhibition, daily aspirin exposure resulted in a paradoxical attenuation of platelet inhibition in response to epinephrine and ADP over time in women but not in men.