| Title: | Proteomics-Based Soluble Urokinase Plasminogen Activator Receptor Levels Are Associated With Incident Heart Failure Risk |
| Journal: | JACC Advances |
| Published: | 1 Jan 2025 |
| DOI: | https://doi.org/10.1016/j.jacadv.2024.101442 |
| URL: | http://dx.doi.org/10.1016/j.jacadv.2024.101442 |
Publication 13722
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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 (R 2 = 0.76 vs 0.73, P < 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.</p>
12 Authors
- Adithya K. Yadalam
- Matthew E. Gold
- Krishan J. Patel
- Chang Liu
- Alexander C. Razavi
- Vardhmaan Jain
- Nishant Vatsa
- Daniel Gold
- Muhammad Owais
- Nisreen Haroun
- Yan V. Sun
- Arshed A. Quyyumi
1 Application
| Application ID | Title |
|---|---|
| 34031 | Integrative study of genomic, environmental, and clinical factors for cardio-metabolic diseases |
Enabling scientific discoveries that improve human health