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可溶性尿激酶型纤溶酶原激活物受体与行冠状动脉造影患者的长期预后。

Soluble urokinase plasminogen activation receptor and long-term outcomes in persons undergoing coronary angiography.

机构信息

Department of Nephrology, University of Heidelberg, Heidelberg, Germany.

Department of Medicine, Rush University Medical Center, 1735 West Congress Parkway, Suite 1004, Chicago, IL, 60612, USA.

出版信息

Sci Rep. 2019 Jan 24;9(1):475. doi: 10.1038/s41598-018-36960-6.

Abstract

Soluble urokinase plasminogen activation receptor (suPAR) is risk factor for kidney disease and biomarker for cardiovascular outcomes but long term longitudinal analyses in a large European cohort have not been perfomed. To hus, we studied suPAR in participants of the Ludwigshafen Risk and Cardiovascular Health study over a very long follow-up time of nearly 10 years. We estimated overall risk of all-cause and cardiovascular death by Cox proportional hazards regression according to quartiles of suPAR, including age, sex, use of lipid-lowering drugs, body mass index, diabetes mellitus, hypertension, smoking, lipids, as well as glomerular filtration rate (eGFR), NT-proBNP, interleukin-6 and high-sensitive CRP as covariates. A total of 2940 participants (age 62.7 ± 10.5years) having a median eGFR of 83.8 mL/min/1.73 m were included. The median suPAR concentration was 3010 pg/mL (interquartile range, 2250-3988 pg/mL). Using the lowest quartile of suPAR as the reference, crude hazard ratio for cardiovascular mortality were 1.58 (95% CI 1.16-2.16), 1.85 (95% CI 1.37-2.52) and 2.75 (95% CI 2.03-3.71) in the second, third and fourth quartile, respectively. Adjusting for NT-proBNPeGFR or inflammation (interleukin-6 and high-sensitive CRP) confirmed results. suPAR predicts all-cause and cardiovascular death over a period of ten years in persons undergoing coronary angiography, independent of the natriuretic peptide NT-proBNP, kidney function and of markers of systemic inflammation. Future investigation into a potential causal role of suPAR in cardiovascular disease is warranted.

摘要

可溶性尿激酶型纤溶酶原激活物受体 (suPAR) 是肾脏疾病的风险因素和心血管结局的生物标志物,但在大型欧洲队列中尚未进行长期纵向分析。因此,我们在一项长达近 10 年的随访时间内,对 Ludwigshafen 风险和心血管健康研究的参与者进行了 suPAR 研究。我们根据 suPAR 的四分位数,通过 Cox 比例风险回归估计了全因和心血管死亡的总体风险,包括年龄、性别、降脂药物使用、体重指数、糖尿病、高血压、吸烟、脂质以及肾小球滤过率 (eGFR)、NT-proBNP、白细胞介素-6 和高敏 CRP 作为协变量。共纳入 2940 名(年龄 62.7±10.5 岁)中位 eGFR 为 83.8 mL/min/1.73 m 的参与者。suPAR 浓度的中位数为 3010 pg/mL(四分位距 2250-3988 pg/mL)。以 suPAR 最低四分位数为参考,心血管死亡率的粗危险比分别为 1.58(95%CI 1.16-2.16)、1.85(95%CI 1.37-2.52)和 2.75(95%CI 2.03-3.71)在第二、三和四分位数中。调整 NT-proBNP、eGFR 或炎症(白细胞介素-6 和高敏 CRP)后,结果仍然成立。suPAR 可预测进行冠状动脉造影的个体在十年内发生全因和心血管死亡,与利钠肽 NT-proBNP、肾功能和全身炎症标志物无关。需要进一步研究 suPAR 在心血管疾病中的潜在因果作用。

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