{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T03:01:22Z","timestamp":1792119682578,"version":"4.4.0"},"reference-count":46,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T00:00:00Z","timestamp":1774569600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Institute of Health Carlos III","doi-asserted-by":"crossref","award":["PI14\/00695"],"award-info":[{"award-number":["PI14\/00695"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100004587","name":"Institute of Health Carlos III","doi-asserted-by":"crossref","award":["PI21\/00369"],"award-info":[{"award-number":["PI21\/00369"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"crossref"}]},{"name":"SACYL, Junta Castilla y Le\u00f3n","award":["GRS1030\/A\/14"],"award-info":[{"award-number":["GRS1030\/A\/14"]}]},{"DOI":"10.13039\/501100000780","name":"European Union","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"crossref"}]},{"name":"ISCIII-Sara Borrell Program","award":["CD24\/00120"],"award-info":[{"award-number":["CD24\/00120"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Growth differentiation factor 15 (GDF15) is a stress-responsive cytokine strongly associated with aging, multimorbidity, and cardiovascular disease. Although prior studies have established its prognostic value in high-risk populations, its role in the general population remains less defined. The aim of this study was to determine if there is an association between plasma GDF15 levels, heart disease and mortality in a representative population-based cohort. We analyzed 1532 participants (mean age 55 years; 54.6% women) with available baseline plasma GDF15 concentrations. Participants were stratified according to an optimal cutoff of 1081 pg\/mL, derived from ROC curve analysis for mortality. Associations with prevalent heart disease were assessed using multivariable logistic regression models adjusted for cardiovascular risk factors and NT-proBNP. Mortality was analyzed using Cox proportional hazards models, with model performance evaluated by C-index and time-dependent ROC curves. Individuals with GDF15 &gt; 1081 pg\/mL were older and exhibited a more adverse cardiometabolic profile with higher prevalence of comorbidities. Elevated GDF15 was independently associated with ischemic cardiomyopathy (OR 3.34, 95% CI: 1.38\u20138.11), particularly in men (OR 4.26, 95% CI: 1.40\u201312.96), but not in women. No independent associations were observed with arrhythmias, valvulopathy, or heart failure after adjustment for NT-proBNP. During a median follow-up of 6.2 years, 51 deaths occurred. Elevated GDF15 independently predicted all-cause mortality (HR 2.47, 95% CI: 1.19\u20135.13), though the effect was attenuated after adjustment for NT-proBNP. GDF15 improved model discrimination (\u0394C-index = +0.01; LRT p = 0.011) and showed robust time-dependent predictive ability, with AUCs of 0.76, 0.82, and 0.85 at 2, 4, and 6 years, respectively. In this population-based cohort, elevated GDF15 identified individuals with an adverse health profile, was independently associated with ischemic cardiomyopathy in men, and predicted mortality. Although its incremental predictive value over NT-proBNP was modest, GDF15 could provide complementary biological information and may enhance multimarker strategies for cardiovascular risk stratification in the general population.<\/jats:p>","DOI":"10.3390\/ijms27073078","type":"journal-article","created":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T08:22:36Z","timestamp":1774858956000},"page":"3078","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Growth Differentiation Factor 15 as a Biomarker of Cardiovascular Burden and Mortality in a Population-Based Cohort"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1683-6617","authenticated-orcid":false,"given":"Beatriz","family":"Mart\u00edn-Carro","sequence":"first","affiliation":[{"name":"Department of Cardiology, University Hospital of Salamanca, 37007 Salamanca, Spain"},{"name":"Instituto de Investigaci\u00f3n Biom\u00e9dica de Salamanca (IBSAL), 37007 Salamanca, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Cardiovasculares (CIBER-CV), Instituto de Salud Carlos III, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leticia","family":"Nieto-Garc\u00eda","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University Hospital of Salamanca, 37007 Salamanca, Spain"},{"name":"Instituto de Investigaci\u00f3n Biom\u00e9dica de Salamanca (IBSAL), 37007 Salamanca, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Cardiovasculares (CIBER-CV), Instituto de Salud Carlos III, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clara","family":"S\u00e1nchez-Pablo","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University Hospital of Salamanca, 37007 Salamanca, Spain"},{"name":"Instituto de Investigaci\u00f3n Biom\u00e9dica de Salamanca (IBSAL), 37007 Salamanca, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Cardiovasculares (CIBER-CV), Instituto de Salud Carlos III, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfonso","family":"Romero","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n Biom\u00e9dica de Salamanca (IBSAL), 37007 Salamanca, Spain"},{"name":"Miguel Armijo Primary Care Centre, 37007 Salamanca, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Candelas","family":"P\u00e9rez del Villar","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University Hospital of Salamanca, 37007 Salamanca, Spain"},{"name":"Instituto de Investigaci\u00f3n Biom\u00e9dica de Salamanca (IBSAL), 37007 Salamanca, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Cardiovasculares (CIBER-CV), Instituto de Salud Carlos III, 28029 Madrid, Spain"},{"name":"Faculty of Medicine, University of Salamanca, 37007 Salamanca, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 Carlos","family":"Moyano-Maza","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n Biom\u00e9dica de Salamanca (IBSAL), 37007 Salamanca, Spain"},{"name":"Clinical Biochemistry Department, University Hospital of Salamanca, 37007 Salamanca, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 Mar\u00eda de","family":"Dios","sequence":"additional","affiliation":[{"name":"Periurbana Norte Primary Care Center, 37184 Salamanca, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6658-0883","authenticated-orcid":false,"given":"David","family":"Cembrero-Fuci\u00f1os","sequence":"additional","affiliation":[{"name":"Clinical Biochemistry Department, University Hospital of Salamanca, 37007 Salamanca, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2235-3336","authenticated-orcid":false,"given":"Estefan\u00eda","family":"Iglesias-Colino","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University Hospital of Salamanca, 37007 Salamanca, Spain"},{"name":"Instituto de Investigaci\u00f3n Biom\u00e9dica de Salamanca (IBSAL), 37007 Salamanca, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Cardiovasculares (CIBER-CV), Instituto de Salud Carlos III, 28029 Madrid, Spain"},{"name":"Faculty of Medicine, University of Salamanca, 37007 Salamanca, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paz","family":"Muriel","sequence":"additional","affiliation":[{"name":"La Alamedilla Primary Care Centre, 37003 Salamanca, 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Primary Care Centre, 37900 Salamanca, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-4486-3954","authenticated-orcid":false,"given":"Lydia","family":"Gonz\u00e1lez-Gonz\u00e1lez","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University Hospital of Salamanca, 37007 Salamanca, Spain"},{"name":"Instituto de Investigaci\u00f3n Biom\u00e9dica de Salamanca (IBSAL), 37007 Salamanca, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Concepci\u00f3n","family":"Ledesma","sequence":"additional","affiliation":[{"name":"Pe\u00f1aranda de Bracamonte Primary Care Centre, 37300 Salamanca, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8901-2141","authenticated-orcid":false,"given":"Javier","family":"Maillo-Seco","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University Hospital of Salamanca, 37007 Salamanca, Spain"},{"name":"Instituto de Investigaci\u00f3n Biom\u00e9dica de Salamanca (IBSAL), 37007 Salamanca, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Cardiovasculares (CIBER-CV), Instituto de Salud Carlos III, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7279-8208","authenticated-orcid":false,"given":"Jes\u00fas","family":"Rodr\u00edguez-Nieto","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University Hospital of Salamanca, 37007 Salamanca, Spain"},{"name":"Instituto de Investigaci\u00f3n Biom\u00e9dica de Salamanca (IBSAL), 37007 Salamanca, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Cardiovasculares (CIBER-CV), Instituto de Salud Carlos III, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1819-5742","authenticated-orcid":false,"given":"Luis 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L.","family":"S\u00e1nchez","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University Hospital of Salamanca, 37007 Salamanca, Spain"},{"name":"Instituto de Investigaci\u00f3n Biom\u00e9dica de Salamanca (IBSAL), 37007 Salamanca, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Cardiovasculares (CIBER-CV), Instituto de Salud Carlos III, 28029 Madrid, Spain"},{"name":"Faculty of Medicine, University of Salamanca, 37007 Salamanca, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"716","DOI":"10.1093\/eurheartj\/ehab892","article-title":"European Society of Cardiology: Cardiovascular disease statistics 2021","volume":"43","author":"Timmis","year":"2022","journal-title":"Eur. 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