Yadalam Adithya K, Gold Matthew E, Patel Krishan J, Liu Chang, Razavi Alexander C, Jain Vardhmaan, Vatsa Nishant, Gold Daniel, Owais Muhammad, Haroun Nisreen, Sun Yan V, Quyyumi Arshed A
Emory University School of Medicine, Division of Cardiology, Department of Medicine, Atlanta, Georgia, USA.
Emory University, Rollins School of Public Health, Department of Epidemiology, Atlanta, Georgia, USA.
JACC Adv. 2024 Dec 9;4(1):101442. doi: 10.1016/j.jacadv.2024.101442. eCollection 2025 Jan.
Higher soluble urokinase plasminogen activator receptor (suPAR) levels are associated with adverse outcomes in chronic heart failure (HF).
The authors assessed the association between proteomics-based suPAR levels and incident HF risk in the general population.
In 40,418 UK Biobank participants without HF or coronary artery disease at enrollment, the association between Olink-based suPAR levels measured as relative protein expression levels and incident all-cause, ischemic, and nonischemic HF was analyzed by competing-risk regression, while accounting for all-cause death as a competing risk. The additional variability in incident HF risk attributable to suPAR levels beyond demographics, traditional risk factors, N-terminal pro B-type natriuretic peptide (NT-proBNP), and C-reactive protein (CRP) levels was assessed with nested Cox modeling and likelihood ratio testing.
The mean age was 56 years; 45% were male, and 94% were White. During a median follow-up of 13.7 (IQR: 1.5) years, 1,428 (3.5%) incident HF events occurred. Proteomics-based suPAR levels (per 1-SD) were independently associated with incident HF (subdistribution HR (sHR): 1.37, 95% CI: 1.29-1.46), ischemic HF (sHR: 1.40, 95% CI: 1.28-1.54), and nonischemic HF (sHR: 1.32, 95% CI: 1.21-1.44) risk, after adjustment for demographics, traditional cardiovascular risk factors, NT-proBNP, and CRP levels. The addition of suPAR levels to a base risk factor model significantly improved the explained variability of incident HF risk ( = 0.76 vs 0.73, < 0.001).
Independent of demographics, traditional risk factors, NT-proBNP, and CRP levels, proteomics-based suPAR levels were significantly associated with incident all-cause, ischemic, and nonischemic HF risk. Proteomics-based measurement of suPAR levels may underestimate the effect size of this relationship.
较高的可溶性尿激酶型纤溶酶原激活物受体（suPAR）水平与慢性心力衰竭（HF）的不良预后相关。
作者评估了基于蛋白质组学的suPAR水平与普通人群中HF发病风险之间的关联。
在40418名入组时无HF或冠状动脉疾病的英国生物银行参与者中，通过竞争风险回归分析了以相对蛋白表达水平衡量的基于Olink的suPAR水平与全因、缺血性和非缺血性HF发病之间的关联，同时将全因死亡作为竞争风险进行考量。通过嵌套Cox模型和似然比检验评估了除人口统计学、传统风险因素、N末端B型利钠肽原（NT-proBNP）和C反应蛋白（CRP）水平之外，suPAR水平导致的HF发病风险的额外变异性。
平均年龄为56岁；45%为男性，94%为白人。在中位随访13.7（四分位间距：1.5）年期间，发生了1428例（3.5%）HF发病事件。在调整了人口统计学、传统心血管风险因素、NT-proBNP和CRP水平后，基于蛋白质组学的suPAR水平（每增加1个标准差）与HF发病（亚分布风险比（sHR）：1.37，95%置信区间：1.29 - 1.46）、缺血性HF（sHR：1.40，95%置信区间：1.28 - 1.54）和非缺血性HF（sHR：1.32，95%置信区间：1.21 - 1.44）风险独立相关。将suPAR水平添加到基础风险因素模型中显著提高了对HF发病风险的解释变异性（χ² = 0.76对0.73，P < 0.001）。
独立于人口统计学、传统风险因素、NT-proBNP和CRP水平，基于蛋白质组学的suPAR水平与全因、缺血性和非缺血性HF发病风险显著相关。基于蛋白质组学的suPAR水平测量可能低估了这种关系的效应大小。
