Proteomics-Based Soluble Urokinase Plasminogen Activator Receptor Levels Are Associated With Incident Heart Failure Risk.

Background: Higher soluble urokinase plasminogen activator receptor (suPAR) levels are associated with adverse outcomes in chronic heart failure (HF).

Objectives: The authors assessed the association between proteomics-based suPAR levels and incident HF risk in the general population.

Methods: 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.

Results: 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).

Conclusions: 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.