从外周动脉疾病患者中得出的血小板反应性指数可预测心血管风险
从外周动脉疾病患者中得出的血小板反应性指数可预测心血管风险
血小板是动脉粥样硬化血栓形成的关键介质，然而用于识别血小板表型高反应性个体的工具却很有限。在这项研究中，我们调查了血小板高反应性与心血管事件的关系，并介绍了一种工具--血小板反应性指数评分（PRESS），它综合了血小板聚集反应和 RNA 测序。在外周动脉疾病（PAD）患者中，对0.4 µM肾上腺素有高反应性血小板反应（60%聚集）的患者30天内主要心血管终点的发生率较高（37.2%对无高反应性患者的15.3%，调整HR 2.76，95% CI 1.5-5.1，P = 0.002）。PRESS 能很好地识别 PAD 患者的高反应表型（AUC [交叉验证] 0.81，95% CI 0.68 -0.94，n = 84）和独立的健康参与者队列（AUC [验证] 0.77，95% CI 0.75 -0.79，n = 35）。经过多变量调整后，PRESS 评分高于中位数的 PAD 患者未来发生心血管事件的风险更高（调整后 HR 1.90，CI 1.07-3.36；P = 0.027，n = 129，NCT02106429）。本研究得出并验证了 PRESS 鉴别血小板高反应性和识别心血管风险增加者的能力。未来有必要在更大的独立队列中进行研究，以进一步验证其有效性。血小板反应性表达评分的开发为降低心血管风险的个性化抗血栓治疗提供了可能。
Platelets are key mediators of atherothrombosis, yet, limited tools exist to identify individuals with a hyperreactive platelet phenotype. In this study, we investigate the association of platelet hyperreactivity and cardiovascular events, and introduce a tool, the Platelet Reactivity ExpreSsion Score (PRESS), which integrates platelet aggregation responses and RNA sequencing. Among patients with peripheral artery disease (PAD), those with a hyperreactive platelet response (>60% aggregation) to 0.4 µM epinephrine had a higher incidence of the 30 day primary cardiovascular endpoint (37.2% vs. 15.3% in those without hyperreactivity, adjusted HR 2.76, 95% CI 1.5–5.1,p = 0.002). PRESS performs well in identifying a hyperreactive phenotype in patients with PAD (AUC [cross-validation] 0.81, 95% CI 0.68 –0.94,n = 84) and in an independent cohort of healthy participants (AUC [validation] 0.77, 95% CI 0.75 –0.79,n = 35). Following multivariable adjustment, PAD individuals with a PRESS score above the median are at higher risk for a future cardiovascular event (adjusted HR 1.90, CI 1.07–3.36;p = 0.027,n = 129, NCT02106429). This study derives and validates the ability of PRESS to discriminate platelet hyperreactivity and identify those at increased cardiovascular risk. Future studies in a larger independent cohort are warranted for further validation. The development of a platelet reactivity expression score opens the possibility for a personalized approach to antithrombotic therapy for cardiovascular risk reduction.