循环microRNA-223水平与急性冠脉综合征患者的血小板反应及临床预后相关性的研究

目的　研究血浆microRNA-223（miR-223）表达水平与急性冠脉综合征（ACS）患者服用氯吡格雷后血小板反应及临床预后的关系。方法　连续纳入接受经皮冠状动脉介入治疗（PCI）的ACS患者208例，术前均接受负荷剂量的氯吡格雷+阿司匹林的双联抗血小板聚集治疗（DAPT）。采用实时荧光定量PCR（qPCR）检测血浆miR-223表达水平，流式细胞术检测血小板反应指数（PRI）。根据PRI中位数将患者分为低PRI组（PRI≤56.3%）和高PRI组（PRI>56.3%），各104例。比较2组患者血浆miR-223表达水平和主要临床及生化指标。随访2年，通过Cox比例风险回归分析血浆miR-223表达水平、PRI、肌钙蛋白I（TnI）、B型钠尿肽（BNP）等指标对主要不良心血管事件（MACE）的影响因素。通过受检者工作特征（ROC）曲线评价血浆miR-223、PRI对MACE的预测能力。结果　miR-223表达水平与PRI呈负相关（rs=-0.420，P＜0.05）。低PRI组患者血浆miR-223表达水平高于高PRI组［（1.15（0.58，1.80） vs. 0.64（0.26，1.08），Z=0.471，P＜0.05］。30例（14.4%）患者发生MACE，低PRI组MACE发生率低于高PRI组（P＜0.05）。Cox比例风险回归分析显示，血浆miR-223和PRI是ACS患者发生MACE的独立预测因子。血浆miR-223和PRI预测ACS患者发生MACE的ROC曲线下面积分别为0.700（95%CI：0.609~0.791，P＜0.05）和0.710（95%CI：0.606~0.815，P＜0.05）。结论　循环miR-223表达水平与ACS患者服用氯吡格雷后PRI呈负相关，循环miR-223和PRI是ACS患者PCI术后MACE的独立预测因子。

Correlation research between circulating microRNA-223 and platelet activity and prognosis in patients with acute coronary syndrome

Objective　To investigate the relationship between the expression level of plasma microRNA-223 (miR-223) and platelet reactivity as well as clinical prognosis in patients with acute coronary syndrome (ACS) after clopidogrel administration. Methods　A total of 208 ACS patients received percutaneous coronary intervention (PCI) were enrolled consecutively. All patients were treated with loading doses of clopidogrel combined with aspirin (DAPT) before intervention. Real-time PCR was used to quantify the expression level of plasma miR-223, and the platelet reactive index (PRI) was quantified through flow cytometry. Patients were divided into two groups according to the PRI median, low PRI group (PRI≤56.3%) and high PRI group (PRI>56.3%), with 104 cases in each group. Plasma miR-223 expression levels, basic clinical data and biochemical index were compared between two groups of patients. After 2-year follow-up, Cox proportional risk regression analysis was used to estimate the influencing factors of plasma miR-223 level, PRI, troponin I (TnI), B-type natriuretic peptide (BNP) and other parameters for major adverse cardiovascular events (MACE). The receiver operating characteristic (ROC) curve was plotted to evaluate the predictive ability of plasma miR-223 and PRI levels for MACE. Results　The level of circulating miR-223 was negatively correlated with PRI (rs=-0.420, P＜0.05), and miR-223 expression level was significantly higher in low PRI group compared with that of high PRI group [1.15 (0.58，1.80) vs.0.64 (0.26，1.08), Z=0.471, P＜0.05]. MACE occurred in 30 patients (14.4%), and the incidence of MACE was lower in low PRI group than that in high PRI group (P < 0.05). Cox proportional risk regression analysis showed that the plasma miR-223 level and PRI were independent risk factors for predicting MACE in ACS patients. The AUC of plasma miR-223 and PRI for predicting the occurrence of MACE in ACS patients was 0.700 (95%CI: 0.609-0.791, P＜0.05) and 0.710 (95%CI: 0.606-0.815, P＜0.05), respectively. Conclusion　The circulating miR-223 level is negatively correlated with PRI in ACS patients after taking clopidogrel. The circulating miR-223 level and PRI are independent factors for predicting MACE in ACS patients after PCI.