{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T20:29:03Z","timestamp":1793046543251,"version":"4.5.0"},"reference-count":37,"publisher":"Oxford University Press (OUP)","issue":"44","license":[{"start":{"date-parts":[[2019,9,26]],"date-time":"2019-09-26T00:00:00Z","timestamp":1569456000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000780","name":"European Commission","doi-asserted-by":"publisher","award":["FP7-242209-BIOSTAT-CHF"],"award-info":[{"award-number":["FP7-242209-BIOSTAT-CHF"]}],"id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,11,21]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Aims<\/jats:title>\n                  <jats:p>Iron deficiency (ID) is common in heart failure (HF) patients and negatively impacts symptoms and prognosis. The aetiology of ID in HF is largely unknown. We studied determinants and the biomarker profile of ID in a large international HF cohort.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods and results<\/jats:title>\n                  <jats:p>We studied 2357 worsening HF patients from the BIOSTAT-CHF cohort. ID was defined as transferrin saturation &amp;lt;20%. Univariable and multivariable logistic regression models were constructed to identify determinants for ID. We measured 92 cardiovascular markers (Olink Cardiovascular III) to establish a biomarker profile of ID. The primary endpoint was the composite of all-cause mortality and first HF rehospitalization. Mean age (\u00b1standard deviation) of all patients was 69\u2009\u00b1\u200912.0\u2009years, 26.1% were female and median N-terminal pro B-type natriuretic peptide levels (+interquartile range) were 4305 (2360\u20138329) ng\/L. Iron deficiency was present in 1453 patients (61.6%), with highest prevalence in females (71.1% vs. 58.3%; P\u2009&amp;lt;\u20090.001). Independent determinants of ID were female sex, lower estimated protein intake, higher heart rate, presence of peripheral oedema and orthopnoea, chronic kidney disease, lower haemoglobin, higher C-reactive protein levels, lower serum albumin levels, and P2Y12 inhibitor use (all P\u2009&amp;lt;\u20090.05). None of these determinants were sex-specific. The biomarker profile of ID largely consisted of pro-inflammatory markers, including paraoxonase 3 (PON3) and tartrate-resistant acid phosphatase type 5. In multivariable Cox proportional hazard regression analyses, ID was associated to worse outcome, independently of predictors of ID (hazard ratio 1.25, 95% confidence interval 1.06\u20131.46; P\u2009=\u20090.007).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Our data suggest that the aetiology of ID in worsening HF is complex, multifactorial and seems to consist of a combination of reduced iron uptake (malnutrition, fluid overload), impaired iron storage (inflammation, chronic kidney disease), and iron loss (antiplatelets).<\/jats:p>\n                  <jats:p\/>\n               <\/jats:sec>","DOI":"10.1093\/eurheartj\/ehz680","type":"journal-article","created":{"date-parts":[[2019,9,11]],"date-time":"2019-09-11T11:51:35Z","timestamp":1568202695000},"page":"3616-3625","source":"Crossref","is-referenced-by-count":105,"title":["Iron deficiency in worsening heart failure is associated with reduced estimated protein intake, fluid retention, inflammation, and antiplatelet use"],"prefix":"10.1093","volume":"40","author":[{"given":"Haye H","family":"van der Wal","sequence":"first","affiliation":[{"name":"Department of Cardiology, University of Groningen, University Medical Centre Groningen , Hanzeplein 1, RB Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4629-9960","authenticated-orcid":false,"given":"Niels","family":"Grote Beverborg","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University of Groningen, University Medical Centre Groningen , Hanzeplein 1, RB Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth","family":"Dickstein","sequence":"additional","affiliation":[{"name":"University of Bergen , Bergen, Norway"},{"name":"Stavanger University Hospital, Gerd-Ragna Bloch Thorsens Gate 8 , Stavanger, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3331-7314","authenticated-orcid":false,"given":"Stefan D","family":"Anker","sequence":"additional","affiliation":[{"name":"Division of Cardiology and Metabolism-Heart Failure , Cachexia & Sarcopenia; Department of Cardiology (CVK), Berlin-Brandenburg Center for Regenerative Therapies (BCRT), German Centre for Cardiovascular Research (DZHK) partner site Berlin, Charit\u00e9 University Medicine, Charit\u00e9pl. 1, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chim C","family":"Lang","sequence":"additional","affiliation":[{"name":"Division of Molecular and Clinical Medicine, School of Medicine, University of Dundee , Ninewells Hospital & Medical School, Dundee, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6553-5749","authenticated-orcid":false,"given":"Leong L","family":"Ng","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Sciences, University of Leicester , Groby Road, Leicester, UK"},{"name":"NIHR Leicester Biomedical Research Unit, Glenfield Hospital , Groby Road, Leicester, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dirk J","family":"van Veldhuisen","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University of Groningen, University Medical Centre Groningen , Hanzeplein 1, RB Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriaan A","family":"Voors","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University of Groningen, University Medical Centre Groningen , Hanzeplein 1, RB Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"van der Meer","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University of Groningen, University Medical Centre Groningen , Hanzeplein 1, RB Groningen, The Netherlands"},{"name":"Department of Cardiology, University of Groningen, University Medical Centre Groningen , Hanzeplein 1, RB Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,9,26]]},"reference":[{"key":"2022102610281010200_ehz680-B1","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1016\/j.ahj.2013.01.017","article-title":"Iron deficiency in chronic heart failure: an international pooled analysis","volume":"165","author":"Klip","year":"2013","journal-title":"Am Heart J"},{"key":"2022102610281010200_ehz680-B2","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1038\/nrcardio.2011.77","article-title":"Anemia and iron deficiency in heart failure: mechanisms and therapeutic approaches","volume":"8","author":"van Veldhuisen","year":"2011","journal-title":"Nat Rev 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