{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,12]],"date-time":"2026-11-12T05:52:07Z","timestamp":1794462727211,"version":"4.9.1"},"reference-count":37,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T00:00:00Z","timestamp":1790294400000},"content-version":"am","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100018890","name":"Dutch Cardiovascular Alliance","doi-asserted-by":"publisher","award":["2020B008 RECONNEXT"],"award-info":[{"award-number":["2020B008 RECONNEXT"]}],"id":[{"id":"10.13039\/100018890","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100018890","name":"Dutch Cardiovascular Alliance","doi-asserted-by":"publisher","award":["2020B004 IMPRESS"],"award-info":[{"award-number":["2020B004 IMPRESS"]}],"id":[{"id":"10.13039\/100018890","id-type":"DOI","asserted-by":"publisher"}]},{"name":"EU\/EFPIA Innovative Medicines Initiative 2 Joint Undertaking BigData@Heart","award":["116074"],"award-info":[{"award-number":["116074"]}],"id":[{"id":"https:\/\/ror.org\/019af4n30","id-type":"ROR","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100018722","name":"Jaap Schouten Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100018722","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Noordwest Academie"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Heart failure (HF) is a systemic syndrome affecting multiple organs. Organ age gaps (OAGs), quantifying organ-level ageing from plasma proteomics, are linked to organ-specific disease including HF, but have been studied exclusively cross-sectionally. We examined how organ-specific ageing evolves within individuals over the course of HF and whether it carries prognostic information beyond established HF markers.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We studied two complementary cohorts with repeated plasma proteomic profiling: 557 individuals including those at risk for HF, pre-HF, and newly diagnosed HF (HELPFul, mainly HFpEF) and 382 patients with established HF (Bio-SHiFT, all LVEF &amp;lt; 50%). OAGs for five organs plus a conventional clock were z-scored. Within each cohort, we modelled longitudinal OAG trajectories using linear mixed-effects models, and, in Bio-SHiFT, related OAGs to the primary endpoint using Cox models with progressive adjustment up to NT-proBNP and troponin T.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Baseline OAGs differed across HF severity in both cohorts. Longitudinally, 50 HELPFul individuals with LVDD showed increasing artery and immune OAGs over 4.6 years. In Bio-SHiFT, event-free patients had stable trajectories, whereas those with adverse events showed sharply accelerating multi-organ ageing over 2.1 years (immune \u03b2 = 0.36 z-score per year, 95% CI 0.26\u20130.47; heart \u03b2 = 0.29, 95% CI 0.17\u20130.40). Higher OAGs predicted the primary endpoint, and the kidney, lung, and immune OAGs remained prognostic after full adjustment including NT-proBNP and troponin T.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>In this exploratory study, multi-organ ageing accelerated before adverse events, and the kidney, lung, and immune OAGs predicted outcome independently of conventional severity markers, supporting a dynamic, organ-level view of HF risk that warrants confirmation in larger cohorts.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/ejhf\/xuag298","type":"journal-article","created":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T11:26:13Z","timestamp":1790335573000},"source":"Crossref","is-referenced-by-count":1,"title":["Longitudinal proteomic organ-specific ageing in heart failure"],"prefix":"10.1093","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5295-0361","authenticated-orcid":false,"given":"Kaiyong","family":"Qu","sequence":"first","affiliation":[{"name":"Laboratory of Experimental Cardiology, University Medical Center Utrecht, Utrecht University , 3584 CX Utrecht ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4313-4290","authenticated-orcid":false,"given":"Ernest","family":"Diez Benavente","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Cardiology, University Medical Center Utrecht, Utrecht University , 3584 CX Utrecht ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ezgi Hatip","family":"\u00dcnl\u00fc","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Thorax Center, Cardiovascular Institute, Erasmus University Medical Center , Rotterdam ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne-Mar L N","family":"van Ommen","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Cardiology, University Medical Center Utrecht, Utrecht University , 3584 CX Utrecht ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M Louis","family":"Handoko","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University Medical Center Utrecht, Utrecht University , Utrecht ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arco J","family":"Teske","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University Medical Center Utrecht, Utrecht University , Utrecht ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maarten Jan","family":"Cramer","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University Medical Center Utrecht, Utrecht University , Utrecht ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Folkert W","family":"Asselbergs","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Amsterdam Cardiovascular Sciences, Amsterdam University Medical Center, University of Amsterdam , Amsterdam ,","place":["The Netherlands"]},{"name":"The National Institute for Health Research University College London Hospitals Biomedical Research Centre, University College London , London ,","place":["UK"]},{"name":"Institute of Health Informatics, University College London , London ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frans H","family":"Rutten","sequence":"additional","affiliation":[{"name":"The National Institute for Health Research University College London Hospitals Biomedical Research Centre, University College London , London ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2559-7128","authenticated-orcid":false,"given":"Eric","family":"Boersma","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Thorax Center, Cardiovascular Institute, Erasmus University Medical Center , Rotterdam ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hester M","family":"den Ruijter","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Cardiology, University Medical Center Utrecht, Utrecht University , 3584 CX Utrecht ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N Charlotte","family":"Onland-Moret","sequence":"additional","affiliation":[{"name":"Department of General Practice & Nursing Science, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University , Utrecht ,","place":["The 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