{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T09:58:16Z","timestamp":1793354296109,"version":"4.5.0"},"reference-count":41,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2025,1,16]],"date-time":"2025-01-16T00:00:00Z","timestamp":1736985600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"NIH\/NHLBI","award":["R01 HL134320"],"award-info":[{"award-number":["R01 HL134320"]}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012737","name":"Department of Health and Human Services","doi-asserted-by":"publisher","award":["75N92022D00001, 75N92022D00002, 75N92022D00003, 75N92022D00004"],"award-info":[{"award-number":["75N92022D00001, 75N92022D00002, 75N92022D00003, 75N92022D00004"]}],"id":[{"id":"10.13039\/100012737","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012737","name":"Department of Health and Human Services","doi-asserted-by":"publisher","award":["75N92022D00005"],"award-info":[{"award-number":["75N92022D00005"]}],"id":[{"id":"10.13039\/100012737","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,8,25]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Hepcidin regulates plasma and tissue iron levels. We studied the association of hepcidin levels with the risk of incident heart failure (HF) and cardiac dysfunction in older adults.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>We included adults from the ongoing, longitudinal Atherosclerosis Risk in Communities (ARIC) study, who were free from prevalent anaemia and HF at Visit 5 (2011\u201313) and had available hepcidin and covariate data. Associations of plasma hepcidin levels with overall adjudicated incident HF, HF with reduced ejection fraction (HFrEF), and HF with preserved ejection fraction (HFpEF) were assessed using multivariable Cox proportional hazards regression models. Cross-sectional associations of hepcidin with echocardiographic measures of cardiac structure and function were estimated using multivariable linear regression models. The mean age was 75 \u00b1 5 years old, and 56% were women. In fully adjusted models, lower hepcidin levels were associated with a higher risk of overall incident HF [hazard ratio [HR] [95% confidence interval (CI) per 50% lower hepcidin]: 1.15 [1.05\u20131.26]; P = 0.003] and HFpEF [HR (95% CI): 1.25 (1.10\u20131.42); P = 0.001]. Plasma hepcidin level was not significantly associated with the risk of incident HFrEF [HR (95% CI): 1.08 (0.94\u20131.24); P = 0.30]. Lower hepcidin levels were associated with higher E wave (P = 0.046), higher E\/e\u2032 ratio (P = 0.002), higher left atrial volume index (P = 0.005), and higher pulmonary artery systolic pressure (P = 0.02).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>In community-dwelling older adults without anaemia, lower plasma hepcidin levels associate with a higher risk of incident HF (particularly HFpEF) and diastolic dysfunction.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/eurjpc\/zwaf018","type":"journal-article","created":{"date-parts":[[2025,1,16]],"date-time":"2025-01-16T11:56:16Z","timestamp":1737028576000},"page":"993-1000","source":"Crossref","is-referenced-by-count":10,"title":["Hepcidin, incident heart failure, and cardiac dysfunction in older adults: the ARIC study"],"prefix":"10.1093","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9412-1668","authenticated-orcid":false,"given":"Iman A F","family":"Aboelsaad","sequence":"first","affiliation":[{"name":"Department of Pharmacy, Brigham and Women\u2019s Hospital , 75 Francis Street, Boston MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4215-9218","authenticated-orcid":false,"given":"Brian L","family":"Claggett","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine, Brigham and Women's Hospital , 75 Francis Street, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria","family":"Lamberson","sequence":"additional","affiliation":[{"name":"Division of Cardiology, University of Texas Southwestern Medical Center , 5323 Harry Hines Boulevard, Dallas, TX 75390, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7764-0802","authenticated-orcid":false,"given":"Pranav","family":"Dorbala","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine, Brigham and Women's Hospital , 75 Francis Street, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7179-718X","authenticated-orcid":false,"given":"Kunihiro","family":"Matsushita","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health , 615 N Wolfe St, Baltimore, MD 21205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1572-1340","authenticated-orcid":false,"given":"Pamela","family":"Lutsey","sequence":"additional","affiliation":[{"name":"Division of Epidemiology & Community Health, University of Minnesota School of Public Health , 451 West Bank Office Building, Minneapolis, MN 55454, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bing","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, University of Texas Health Science Center at Houston School of Public Health , 1200 Pressler Street, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0630-6505","authenticated-orcid":false,"given":"Brandon W","family":"Lennep","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Mississippi, University , MS 38677, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youssef M K","family":"Farag","sequence":"additional","affiliation":[{"name":"Alexion\/AstraZeneca, 121 Seaport Boulevard , Boston, MA 02210, USA"},{"name":"Harvard Medical School , 25 Shattuck Street, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amil M","family":"Shah","sequence":"additional","affiliation":[{"name":"Division of Cardiology, University of Texas Southwestern Medical Center , 5323 Harry Hines Boulevard, Dallas, TX 75390, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1570-1486","authenticated-orcid":false,"given":"Leo F","family":"Buckley","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Brigham and Women\u2019s Hospital , 75 Francis Street, Boston MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,1,16]]},"reference":[{"key":"2025082511023770900_zwaf018-B1","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1002\/ejhf.701","article-title":"Ferritin levels and risk of heart failure-the Atherosclerosis Risk in Communities Study","volume":"19","author":"Silvestre","year":"2017","journal-title":"Eur J Heart Fail"},{"key":"2025082511023770900_zwaf018-B2","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1002\/ejhf.622","article-title":"Serum ferritin and risk for new-onset heart failure and cardiovascular events in the community","volume":"19","author":"Klip","year":"2017","journal-title":"Eur J Heart Fail"},{"key":"2025082511023770900_zwaf018-B3","doi-asserted-by":"crossref","first-page":"522","DOI":"10.2215\/CJN.15360920","article-title":"Heart failure hospitalization risk associated with iron status in veterans with CKD","volume":"16","author":"Cho","year":"2021","journal-title":"Clin J Am Soc Nephrol"},{"key":"2025082511023770900_zwaf018-B4","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1093\/eurheartj\/ehs377","article-title":"Iron status in patients with chronic heart failure","volume":"34","author":"Jankowska","year":"2013","journal-title":"Eur Heart J"},{"key":"2025082511023770900_zwaf018-B5","doi-asserted-by":"crossref","first-page":"910","DOI":"10.1002\/ejhf.1154","article-title":"Iron deficiency impairs contractility of human cardiomyocytes through decreased mitochondrial function","volume":"20","author":"Hoes","year":"2018","journal-title":"Eur J Heart Fail"},{"key":"2025082511023770900_zwaf018-B6","first-page":"362","article-title":"Iron-regulatory proteins secure iron availability in cardiomyocytes to prevent heart failure","volume":"38","author":"Haddad","year":"2017","journal-title":"Eur Heart J"},{"key":"2025082511023770900_zwaf018-B7","doi-asserted-by":"crossref","first-page":"716","DOI":"10.1002\/ejhf.2454","article-title":"Cardiac energetics in patients with chronic heart failure and iron deficiency: an in-vivo 31 P magnetic resonance spectroscopy study","volume":"24","author":"Papalia","year":"2022","journal-title":"Eur J Heart Fail"},{"key":"2025082511023770900_zwaf018-B8","doi-asserted-by":"crossref","first-page":"e014254","DOI":"10.1161\/JAHA.119.014254","article-title":"Noninvasive imaging estimation of myocardial iron repletion following administration of intravenous iron: the Myocardial-IRON Trial","volume":"9","author":"N\u00fa\u00f1ez","year":"2020","journal-title":"J Am Heart Assoc"},{"key":"2025082511023770900_zwaf018-B9","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.yjmcc.2021.06.005","article-title":"Systemic iron deficiency does not affect the cardiac iron content and progression of heart failure","volume":"159","author":"Paterek","year":"2021","journal-title":"J Mol Cell Cardiol"},{"key":"2025082511023770900_zwaf018-B10","doi-asserted-by":"crossref","first-page":"e004800","DOI":"10.1161\/CIRCHEARTFAILURE.117.004800","article-title":"Skeletal muscle abnormalities and iron deficiency in chronic heart Failure: an exercise 31P magnetic resonance spectroscopy study of calf muscle","volume":"11","author":"Melenovsky","year":"2018","journal-title":"Circ Heart Fail"},{"key":"2025082511023770900_zwaf018-B11","doi-asserted-by":"crossref","first-page":"2386","DOI":"10.1161\/CIRCULATIONAHA.118.038516","article-title":"Effect of iron isomaltoside on skeletal muscle energetics in patients with chronic heart failure and iron deficiency","volume":"139","author":"Charles-Edwards","year":"2019","journal-title":"Circulation"},{"key":"2025082511023770900_zwaf018-B12","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1146\/annurev-med-043021-032816","article-title":"Hepcidin and iron in health and disease","volume":"74","author":"Nemeth","year":"2023","journal-title":"Annu Rev Med"},{"key":"2025082511023770900_zwaf018-B13","doi-asserted-by":"crossref","first-page":"2663","DOI":"10.1210\/en.2006-1331","article-title":"The iron regulatory peptide hepcidin is expressed in the heart and regulated by hypoxia and inflammation","volume":"148","author":"Merle","year":"2007","journal-title":"Endocrinology"},{"key":"2025082511023770900_zwaf018-B14","doi-asserted-by":"crossref","first-page":"e19804","DOI":"10.7554\/eLife.19804","article-title":"An essential cell-autonomous role for hepcidin in cardiac iron homeostasis","volume":"5","author":"Lakhal-Littleton","year":"2016","journal-title":"eLife"},{"key":"2025082511023770900_zwaf018-B15","doi-asserted-by":"crossref","first-page":"1981","DOI":"10.1182\/blood-2015-05-642223","article-title":"Oral iron supplements increase hepcidin and decrease iron absorption from daily or twice-daily doses in iron-depleted young women","volume":"126","author":"Moretti","year":"2015","journal-title":"Blood"},{"key":"2025082511023770900_zwaf018-B16","doi-asserted-by":"crossref","first-page":"1232","DOI":"10.3324\/haematol.2019.220830","article-title":"Iron absorption from supplements is greater with alternate day than with consecutive day dosing in iron-deficient anemic women","volume":"105","author":"Stoffel","year":"2020","journal-title":"Haematologica"},{"key":"2025082511023770900_zwaf018-B17","doi-asserted-by":"crossref","first-page":"1958","DOI":"10.1001\/jama.2017.5427","article-title":"Effect of oral iron repletion on exercise capacity in patients with heart failure with reduced ejection fraction and iron deficiency: the IRONOUT HF randomized clinical trial","volume":"317","author":"Lewis","year":"2017","journal-title":"JAMA"},{"key":"2025082511023770900_zwaf018-B18","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1002\/ajh.23354","article-title":"Hepcidin levels predict nonresponsiveness to oral iron therapy in patients with iron deficiency anemia","volume":"88","author":"Bregman","year":"2013","journal-title":"Am J Hematol"},{"key":"2025082511023770900_zwaf018-B19","doi-asserted-by":"crossref","first-page":"2032","DOI":"10.1093\/eurjpc\/zwad244","article-title":"Long-term dietary iron intake and risk of non-fatal cardiovascular diseases in the China Health and Nutrition Survey","volume":"30","author":"Chen","year":"2023","journal-title":"Eur J Prev Cardiol"},{"key":"2025082511023770900_zwaf018-B20","doi-asserted-by":"crossref","first-page":"2939","DOI":"10.1016\/j.jacc.2021.04.035","article-title":"The ARIC (atherosclerosis risk in communities) study: JACC focus seminar 3\/8","volume":"77","author":"Wright","year":"2021","journal-title":"J Am Coll Cardiol"},{"key":"2025082511023770900_zwaf018-B21","first-page":"5","article-title":"Nutritional anaemias.","volume":"405","author":"World Health Organization","year":"1968","journal-title":"World Health Organ Tech Rep Ser"},{"key":"2025082511023770900_zwaf018-B22","doi-asserted-by":"crossref","first-page":"e15004","DOI":"10.1371\/journal.pone.0015004","article-title":"Aptamer-based multiplexed proteomic technology for biomarker discovery","volume":"5","author":"Gold","year":"2010","journal-title":"PLoS One"},{"key":"2025082511023770900_zwaf018-B23","doi-asserted-by":"crossref","first-page":"e26332","DOI":"10.1371\/journal.pone.0026332","article-title":"From SOMAmer-based biomarker discovery to diagnostic and clinical applications: a SOMAmer-based, streamlined multiplex proteomic assay","volume":"6","author":"Kraemer","year":"2011","journal-title":"PLoS"},{"key":"2025082511023770900_zwaf018-B24","doi-asserted-by":"crossref","first-page":"1712","DOI":"10.1038\/s41588-021-00978-w","article-title":"Large-scale integration of the plasma proteome with genetics and disease","volume":"53","author":"Ferkingstad","year":"2021","journal-title":"Nat Genet"},{"key":"2025082511023770900_zwaf018-B25","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1038\/s41588-022-01051-w","article-title":"Plasma proteome analyses in individuals of European and African ancestry identify cis-pQTLs and models for proteome-wide association studies","volume":"54","author":"Zhang","year":"2022","journal-title":"Nat Genet"},{"key":"2025082511023770900_zwaf018-B26","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1161\/CIRCHEARTFAILURE.111.963199","article-title":"Classification of heart failure in the Atherosclerosis Risk in Communities (ARIC) study","volume":"5","author":"Rosamond","year":"2012","journal-title":"Circ Heart Fail"},{"key":"2025082511023770900_zwaf018-B27","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1161\/CIRCIMAGING.113.000736","article-title":"Rationale and design of a multicenter echocardiographic study to assess the relationship between cardiac structure and function and heart failure risk in a biracial cohort of community-dwelling elderly persons","volume":"7","author":"Shah","year":"2014","journal-title":"Circ Cardiovasc Imaging"},{"key":"2025082511023770900_zwaf018-B28","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/S0735-1097(02)01938-1","article-title":"Anemia as a risk factor for cardiovascular disease in the atherosclerosis risk in communities (aric) study","volume":"40","author":"Sarnak","year":"2002","journal-title":"J Am Coll Cardiol"},{"key":"2025082511023770900_zwaf018-B29","doi-asserted-by":"crossref","first-page":"e006259","DOI":"10.1161\/JAHA.117.006259","article-title":"Kidney disease measures and left ventricular structure and function: the Atherosclerosis Risk in Communities Study","volume":"6","author":"Matsushita","year":"2017","journal-title":"J Am Heart Assoc"},{"key":"2025082511023770900_zwaf018-B30","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/0895-4356(95)00041-0","article-title":"Community surveillance of coronary heart disease in the Atherosclerosis Risk in Communities (ARIC) study: methods and initial two years\u2019 experience","volume":"49","author":"White","year":"1996","journal-title":"J Clin Epidemiol"},{"key":"2025082511023770900_zwaf018-B31","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/j.ahj.2009.05.010","article-title":"Incidence of atrial fibrillation in whites and African-Americans: the Atherosclerosis Risk in Communities (ARIC) study","volume":"158","author":"Alonso","year":"2009","journal-title":"Am Heart J"},{"key":"2025082511023770900_zwaf018-B32","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1093\/oxfordjournals.aje.a010233","article-title":"Carotid wall thickness is predictive of incident clinical stroke: the Atherosclerosis Risk in Communities (ARIC) study","volume":"151","author":"Chambless","year":"2000","journal-title":"Am J Epidemiol"},{"key":"2025082511023770900_zwaf018-B33","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1007\/s40200-019-00391-5","article-title":"Diabetes mellitus and cancer incidence: the Atherosclerosis Risk in Communities (ARIC) cohort study","volume":"18","author":"Rastad","year":"2019","journal-title":"Diabetes Metab Disord"},{"key":"2025082511023770900_zwaf018-B34","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1016\/j.annepidem.2014.08.004","article-title":"Elevated hepatic enzymes and incidence of venous thromboembolism: a prospective study","volume":"24","author":"Folsom","year":"2014","journal-title":"Ann Epidemiol"},{"key":"2025082511023770900_zwaf018-B35","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.neurobiolaging.2018.03.031","article-title":"The association of mid- to late-life systemic inflammation with white matter structure in older adults: the ARIC study","volume":"68","author":"Walker","year":"2018","journal-title":"Neurobiol Aging"},{"key":"2025082511023770900_zwaf018-B36","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1056\/NEJMoa1114248","article-title":"Estimating glomerular filtration rate from serum creatinine and cystatin C","volume":"367","author":"Inker","year":"2012","journal-title":"N Engl J Med"},{"key":"2025082511023770900_zwaf018-B37","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1038\/s43587-021-00064-0","article-title":"Large-scale plasma proteomic analysis identifies proteins and pathways associated with dementia risk","volume":"1","author":"Walker","year":"2021","journal-title":"Nat Aging"},{"key":"2025082511023770900_zwaf018-B38","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1373\/jalm.2018.027086","article-title":"Reproducibility and variability of protein analytes measured using a multiplexed modified aptamer assay","volume":"4","author":"Tin","year":"2019","journal-title":"J Appl Lab Med"},{"key":"2025082511023770900_zwaf018-B39","doi-asserted-by":"crossref","first-page":"1530","DOI":"10.1161\/CIRCULATIONAHA.118.034545","article-title":"Iron regulator hepcidin impairs macrophage-dependent cardiac repair after injury","volume":"139","author":"Zlatanova","year":"2019","journal-title":"Circulation"},{"key":"2025082511023770900_zwaf018-B40","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1038\/labinvest.2017.111","article-title":"Balance of cardiac and systemic hepcidin and its role in heart physiology and pathology","volume":"98","author":"Vela","year":"2018","journal-title":"Lab Invest"},{"key":"2025082511023770900_zwaf018-B41","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1001\/jama.2015.17346","article-title":"Effect of caloric restriction or aerobic exercise training on peak oxygen consumption and quality of life in obese older patients with heart failure with preserved ejection fraction: a randomized clinical trial","volume":"315","author":"Kitzman","year":"2016","journal-title":"JAMA"}],"container-title":["European Journal of Preventive Cardiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/eurjpc\/advance-article-pdf\/doi\/10.1093\/eurjpc\/zwaf018\/61462094\/zwaf018.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/eurjpc\/article-pdf\/32\/11\/993\/61462094\/zwaf018.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/eurjpc\/article-pdf\/32\/11\/993\/61462094\/zwaf018.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,25]],"date-time":"2025-08-25T15:02:50Z","timestamp":1756134170000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/eurjpc\/article\/32\/11\/993\/7958707"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,16]]},"references-count":41,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2025,1,16]]},"published-print":{"date-parts":[[2025,8,25]]}},"URL":"https:\/\/doi.org\/10.1093\/eurjpc\/zwaf018","relation":{},"ISSN":["2047-4873","2047-4881"],"issn-type":[{"value":"2047-4873","type":"print"},{"value":"2047-4881","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2025,8]]},"published":{"date-parts":[[2025,1,16]]}}}