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