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Alfred Taubman Medical Research Institute","doi-asserted-by":"publisher","award":["Wolfe Scholarship"],"award-info":[{"award-number":["Wolfe Scholarship"]}],"id":[{"id":"10.13039\/100008456","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100019495","name":"Michigan Center on the Demography of Aging, University of Michigan","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100019495","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Inflammation is postulated to be a key pathogenic mechanism in heart failure with preserved ejection fraction (HFpEF). Soluble urokinase plasminogen activator receptor (suPAR), a regulator of innate immune activity, is associated with incident heart failure; however, its role in HFpEF remains unclear. We aimed to elucidate the role of suPAR in HFpEF outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this secondary analysis of the TOPCAT trial's North American cohort, suPAR was measured at baseline and 1 year in a subset of patients with HFpEF (n = 406) treated with either spironolactone or placebo. We assessed the association between suPAR levels and adverse outcomes, whether spironolactone influenced suPAR levels and whether the association between spironolactone and outcomes is dependent on suPAR levels. The primary outcome was a composite of cardiovascular death, cardiac arrest or hospitalization for heart failure management.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The mean age of participants was 69.5 years, and 46.6% were female. After a median follow-up of 2.9 years, 19.9% experienced the primary outcome event. The 5-year cumulative incidence of the primary outcome in the highest tertile of suPAR (&amp;gt;3.93 ng\/mL) was 44%, compared with 14% in the lowest tertile (\u22642.94 ng\/mL) (P = 0.001). Spironolactone did not significantly change suPAR levels at 1 year, nor was its effect on outcomes modified by baseline suPAR (P for interaction = 0.6). In multivariable analysis, each doubling of baseline suPAR levels was associated with nearly twofold increased risk of the primary outcome, independent of traditional risk factors and natriuretic peptide (NP) levels (HR 1.94 [95% CI 1.33\u20132.83]). suPAR's risk discrimination ability was superior and additive to that of NP.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>While suPAR levels independently predict poor outcomes in HFpEF patients, spironolactone does not modulate this inflammatory pathway. The findings suggest that suPAR represents a stable inflammatory biomarker in HFpEF, highlighting the need for further evaluation of targeted anti-inflammatory strategies in this population.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ehf2.15423","type":"journal-article","created":{"date-parts":[[2025,9,18]],"date-time":"2025-09-18T04:15:58Z","timestamp":1758168958000},"page":"4208-4218","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Soluble Urokinase Plasminogen Activator Receptor and Outcomes in HFpEF: A TOPCAT Ancillary Study"],"prefix":"10.1093","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9957-5952","authenticated-orcid":false,"given":"Christina G.","family":"Hutten","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Division of Cardiovascular Medicine, University of Michigan , Ann Arbor, Michigan 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Internal Medicine, Division of Cardiology, University of Texas Medical Branch , Galveston, Texas ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pennelope","family":"Kunkle","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Cardiovascular Medicine, University of Michigan , Ann Arbor, Michigan ,","place":["USA"]},{"name":"Department of Internal Medicine, Division of Cardiology, University of Texas Medical Branch , Galveston, Texas ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sascha N.","family":"Goonewardena","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Cardiovascular Medicine, University of Michigan , Ann Arbor, Michigan ,","place":["USA"]},{"name":"Veteran Affairs Ann Arbor Health System , Ann Arbor, Michigan ,","place":["USA"]},{"name":"Department of Biobehavioral Nursing and Health Informatics, School of Nursing, 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