Proteomics-Based Soluble Urokinase Plasminogen Activator Receptor Levels Are Associated With Incident Heart Failure Risk
JACC: Advances, 2024
Yadalam A., Gold M., Patel K., Liu C., Razavi A., Jain V., Vatsa N., Gold D., Owais M., Haroun N., Sun Y., Quyyumi A.
| Disease area | Application area | Sample type | Products |
|---|---|---|---|
CVD | Patient Stratification | Plasma | O Olink Explore 3072/384 |
Abstract
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 (R2 = 0.76 vs 0.73, P < 0.001).ConclusionsIndependent 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.