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To assess oxidative stress, direct quantification of reactive oxygen species would be ideal but this is not feasible due to their short half-lives. Antioxidant enzymes such as peroxiredoxins, produced as a direct response to oxidative stress, mirror the process and can be more easily quantified. The aim of this study was to examine whether circulating peroxiredoxin-4 (Prx4), a marker of systemic oxidative stress, associates with incident HF and its subtypes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>We included a total of 8199 individuals from the Prevention of REnal and Vascular End-stage Disease (PREVEND) community-based cohort (mean age: 49.8\u2009years; 50.1% women). During a median follow-up of 12.6\u2009years, 349 (4.3%) HF events occurred of which 118 (33.8%) had HF with preserved ejection fraction. In a Cox proportional hazards model adjusting for age, sex, smoking, diabetes, hypertension, obesity, total and high-density lipoprotein cholesterol, cholesterol-lowering medication and renal disease, Prx4 was significantly associated with incident HF (hazard ratio [HR] per 1 standard deviation increase in log-Prx4: 1.22; 95% confidence interval [CI] 1.09\u20131.36; p\u2009&amp;lt;\u20090.001). Among HF subtypes, Prx4 remained associated with incident HF with preserved (HR 1.27; 95% CI 1.05\u20131.53) as well as reduced ejection fraction (HR 1.19; 95% CI 1.04\u20131.37), with no significant difference between the subtypes (p\u2009=\u20090.64).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Circulating Prx4 associates with the risk of developing HF, both with preserved and reduced ejection fraction. Future studies should examine whether Prx4 can serve as a real-time marker of oxidative stress status.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ejhf.3653","type":"journal-article","created":{"date-parts":[[2025,4,6]],"date-time":"2025-04-06T20:25:36Z","timestamp":1743971136000},"page":"905-911","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Peroxiredoxin-4, a Marker of Systemic Oxidative Stress, is Associated with Incident Heart Failure"],"prefix":"10.1093","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7781-2897","authenticated-orcid":false,"given":"Navin","family":"Suthahar","sequence":"first","affiliation":[{"name":"Department of Cardiology, Erasmus MC, Cardiovascular Institute, Thorax Center , Rotterdam ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanne 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