University of Missouri-Kansas City School of Medicine, M4-325, 2411 Holmes St, Kansas City, MO, USA.
Clin Pharmacokinet. 2018 Jun;57(6):663-672. doi: 10.1007/s40262-017-0611-8.
Obesity is an independent risk factor for cardiovascular morbidity and mortality due to atherothrombotic events and represents a group of patients who are in need of optimized antithrombotic therapy. Central to the obesity-related risk of atherothrombosis is a pro-thrombotic state characterized by increased levels of coagulation factors, impaired fibrinolysis, and platelet hyper-reactivity, which results from the interaction among the features clustering in obesity: insulin resistance, inflammation, oxidative stress, and endothelial dysfunction. Aspirin is a cornerstone antiplatelet drug that has substantial interpatient variability in pharmacodynamic response and a number of reports have demonstrated that obesity is a risk factor for a reduced aspirin pharmacodynamic response. The inflammatory state associated with obesity, particularly a metabolic endotoxemia, may set in motion a number of mechanisms that increase platelet reactivity and platelet turnover and decrease aspirin bioavailability, all contributing to a poor aspirin response. A greater understanding of the mechanisms underlying obesity-related high on-aspirin platelet reactivity will help in optimization of antithrombotic therapy in this patient population.
肥胖是动脉粥样血栓事件导致心血管发病率和死亡率的独立危险因素，代表了一群需要优化抗血栓治疗的患者。肥胖相关动脉粥样血栓形成的核心是一种促血栓形成状态，其特征是凝血因子水平升高、纤维蛋白溶解受损和血小板高反应性，这是肥胖症中聚集的特征相互作用的结果：胰岛素抵抗、炎症、氧化应激和内皮功能障碍。阿司匹林是一种基石抗血小板药物，其药效学反应存在很大的个体间变异性，有许多报道表明肥胖是阿司匹林药效学反应降低的一个危险因素。与肥胖相关的炎症状态，特别是代谢性内毒素血症，可能引发多种机制，增加血小板反应性和血小板更新，并降低阿司匹林的生物利用度，所有这些都导致阿司匹林反应不佳。更好地了解肥胖相关的高阿司匹林血小板反应背后的机制将有助于优化这类患者的抗血栓治疗。
