Eapen Danny J, Manocha Pankaj, Ghasemzadeh Nima, Patel Riyaz S, Al Kassem Hatem, Hammadah Muhammad, Veledar Emir, Le Ngoc-Anh, Pielak Tomasz, Thorball Christian W, Velegraki Aristea, Kremastinos Dimitrios T, Lerakis Stamatios, Sperling Laurence, Quyyumi Arshed A
Emory Clinical Cardiovascular Research Institute, Emory University School of Medicine, Atlanta, GA (D.J.E., P.M., N.G., R.S.P., H.A.K., M.H., E.V., N.A.L., S.L., L.S., A.A.Q.).
Emory Clinical Cardiovascular Research Institute, Emory University School of Medicine, Atlanta, GA (D.J.E., P.M., N.G., R.S.P., H.A.K., M.H., E.V., N.A.L., S.L., L.S., A.A.Q.) Department of Medicine, Cardiff University, Cardiff, UK (R.S.P.).
J Am Heart Assoc. 2014 Oct 23;3(5):e001118. doi: 10.1161/JAHA.114.001118.
Soluble urokinase plasminogen activator receptor (suPAR) is an emerging inflammatory and immune biomarker. Whether suPAR level predicts the presence and the severity of coronary artery disease (CAD), and of incident death and myocardial infarction (MI) in subjects with suspected CAD, is unknown.
We measured plasma suPAR levels in 3367 subjects (67% with CAD) recruited in the Emory Cardiovascular Biobank and followed them for adverse cardiovascular (CV) outcomes of death and MI over a mean 2.1±1.1 years. Presence of angiographic CAD (≥50% stenosis in ≥1 coronary artery) and its severity were quantitated using the Gensini score. Cox's proportional hazard survival and discrimination analyses were performed with models adjusted for established CV risk factors and C-reactive protein levels. Elevated suPAR levels were independently associated with the presence of CAD (P<0.0001) and its severity (P<0.0001). A plasma suPAR level ≥3.5 ng/mL (cutoff by Youden's index) predicted future risk of MI (hazard ratio [HR]=3.2; P<0.0001), cardiac death (HR=2.62; P<0.0001), and the combined endpoint of death and MI (HR=1.9; P<0.0001), even after adjustment of covariates. The C-statistic for a model based on traditional risk factors was improved from 0.72 to 0.74 (P=0.008) with the addition of suPAR.
Elevated levels of plasma suPAR are associated with the presence and severity of CAD and are independent predictors of death and MI in patients with suspected or known CAD.
可溶性尿激酶型纤溶酶原激活物受体（suPAR）是一种新出现的炎症和免疫生物标志物。suPAR水平是否能预测冠状动脉疾病（CAD）的存在及严重程度，以及疑似CAD患者发生死亡和心肌梗死（MI）的风险，目前尚不清楚。
我们测量了埃默里心血管生物样本库中3367名受试者（67%患有CAD）的血浆suPAR水平，并在平均2.1±1.1年的时间里对他们进行随访，观察不良心血管（CV）事件死亡和MI的发生情况。通过血管造影确定CAD（≥1支冠状动脉狭窄≥50%）的存在及其严重程度，并使用Gensini评分进行量化。采用Cox比例风险生存分析和判别分析，模型对已确定的CV危险因素和C反应蛋白水平进行了校正。suPAR水平升高与CAD的存在（P<0.0001）及其严重程度（P<0.0001）独立相关。血浆suPAR水平≥3.5 ng/mL（由约登指数确定的临界值）可预测未来发生MI的风险（风险比[HR]=3.2；P<0.0001）、心源性死亡（HR=2.62；P<0.0001）以及死亡和MI的联合终点（HR=1.9；P<0.0001），即使在调整协变量后依然如此。在传统危险因素模型中加入suPAR后，C统计量从0.72提高到0.74（P=0.008）。
血浆suPAR水平升高与CAD的存在和严重程度相关，是疑似或已知CAD患者死亡和MI的独立预测因素。
