Proteomics-Based Soluble Urokinase Plasminogen Activator Receptor Levels Are Associated With Adverse Cardiovascular Outcomes in the General Population: Insights From the UK Biobank.

Authors

Shaimaa M Sakr, Jose R Medina-Inojosa, Chang Liu, Ishwar D Chuckaree, Veena Agusala, Rafia Lodhi, Zara Mecklai, Muhammad Owais, Mahmoud Al Kasem, Wesam Hritani, Muhammet Hasan, Salim Hayek, Yan V Sun, Arshed A Quyyumi

Published in

Journal of the American Heart Association. Pages e047057. Jul 03, 2026. Epub Jul 03, 2026.

Abstract

Elevated soluble urokinase plasminogen activator receptor (suPAR) levels are associated with inflammation, immune activation, and major adverse cardiovascular events in coronary artery disease. Encoded by the PLAUR gene, suPAR levels are influenced by the rs4760 genetic variant. Whether proteomics-based suPAR levels predict adverse outcomes in the general population remains unknown.
Proteomics-based suPAR levels were measured using the Olink Immunoassay in 33 963 UK Biobank participants without known coronary artery disease. Fine-Gray and Cox proportional hazards models assessed associations between suPAR and major adverse cardiovascular events (primary outcome: cardiovascular mortality, nonfatal myocardial infarction, or stroke), cardiovascular mortality, and all-cause mortality (secondary outcomes), after adjustment for demographic and clinical risk factors, hs-CRP (high-sensitivity C-reactive protein), and the rs4760 variant. Incremental discrimination was evaluated using C-statistics.
Participants were aged 56.4 (SD, 8.2) years; 45% were men, and 93.4% were White. Over a median follow-up of 14 years (476 177 person-years), 10.7% experienced major adverse cardiovascular events, 2.6% experienced cardiovascular mortality, and 9.4% experienced all-cause mortality. Each 1-SD increment in proteomics-based suPAR was associated with significantly higher risk of major adverse cardiovascular events (hazard ratio [HR], 3.2 [95% CI, 2.9-4.5]), cardiovascular mortality (HR, 5.9 [95% CI, 5.1-6.9]), and all-cause mortality (HR, 5.0 [95% CI, 4.6-5.5]), independent of clinical risk factors and hs-CRP. Additional adjustment for rs4760 did not attenuate these associations. Proteomics-based suPAR significantly improved discrimination beyond clinical risk factors (C-statistic: 0.719 versus 0.732; P<0.001).
Proteomics-based suPAR independently predicts adverse cardiovascular outcomes in the general population, beyond conventional risk factors, hs-CRP, and genetic predisposition to elevated suPAR levels.

PMID:
42396825
Bibliographic data and abstract were imported from PubMed on 03 Jul 2026.

Read full publication at:
Please sign in to see all details.

Stats

1-terrible, 9-excellent. How would you rate this publication? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.