Modulators of platelet function in aging

Abstract

Platelets are small, anucleated effector cells that play an important role in linking the hemostatic and inflammatory processes in the body. Platelet function is known to be altered under various inflammatory conditions including aging. A gain in platelet function during aging can increase the risk of thrombotic events, such as stroke and acute myocardial infarction. Anti-platelet therapy is designed to reduce risk of serious cerebrovascular and cardiovascular events, but the adverse consequences of therapy, such as risk for bleeding increases with aging as well. Age-associated comorbidities such as obesity, diabetes, and hyperlipidemia also contribute to increased platelet activity and thus can enhance the risk of thrombosis. Therefore, identification of unique mechanisms of platelet dysfunction in aging and in age-associated comorbidities is warranted to design novel antiplatelet drugs. This review outlines some of the current areas of research on aging-related mechanisms of platelet hyperactivity and addresses the clinical urgency for designing anti-platelet therapies toward novel molecular targets in the aging population.     

不同双重抗血小板治疗时间对药物洗脱支架极晚期血栓患者预后的影响

目的：分析药物洗脱支架（DES）术后发生极晚期支架内血栓（VLST）的患者接受双重抗血小板治疗（DAPT）的情况,探讨不同DAPT持续时间对患者远期预后的影响。方法2006年1月至2013年2月,首都医科大学附属北京朝阳医院心脏中心共完成3945例急诊冠状动脉造影,入选经急诊造影证实为VLST的患者。根据随访期间是否仍持续使用DAPT,将患者分为持续DAPT组和对照组。比较两组患者的临床资料、造影及介入治疗资料以及抗血小板药物治疗情况。临床主要不良心血管事件（MACE）包括随访期间的非致死性心肌梗死（MI）,再发支架内血栓（ST）,靶血管重建率（TVR）以及死亡。探讨不同DAPT持续时间对患者远期预后的影响,并分析随访期间发生MACE的预测因素。结果共计有62例VLST患者纳入研究,其中男性55例,女性7例,年龄41～82（58.6±10.2）岁。VLST距第1次DES置入时间为12.5～84（38.7±18.1）个月。住院期间脑出血死亡1例,存活的61例患者随访5～88（32.1±19.1）个月。随访期间,又有17例患者出现MACE,Kaplan-Meier生存率分析提示无事件生存率为45.1%。末次随访时,坚持持续DAPT的患者38例,其中5例（13.2%）发生MACE,事件发生率明显低于对照组（54.2%,P＝0.001）。根据是否发生MACE事件将所有患者分为两组,Cox单因素分析提示再次置入第一代DES[危害率（hazard ratio,HR）：2.69,P＝0.04]和持续DAPT（HR：0.25,P＝0.01）为远期随访中MACE相关的预测因素。而多因素Cox分析则提示仅有持续DAPT是随访期间不发生MACE的唯一预测因素（HR：0.30,95% CI：0.09～0.97,P＝0.04）。结论 DES术后VLST患者远期预后情况欠佳,事件发生率较高。坚持DAPT可能有助于减少远期不良事件的发生。