{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:03:43Z","timestamp":1785542623430,"version":"3.56.0"},"reference-count":52,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2021,12,9]],"date-time":"2021-12-09T00:00:00Z","timestamp":1639008000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000780","name":"European Commission","doi-asserted-by":"publisher","award":["FP7\u2010242209\u2010BIOSTAT\u2010CHF"],"award-info":[{"award-number":["FP7\u2010242209\u2010BIOSTAT\u2010CHF"]}],"id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["European J of Heart Fail"],"published-print":{"date-parts":[[2022,1]]},"abstract":"<jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Whereas the combination of anaemia and chronic kidney disease (CKD) has been extensively studied in patients with heart failure (HF), the contribution of iron deficiency (ID) to this dysfunctional interplay is unknown. We aimed to assess clinical associates and pathophysiological pathways related to ID in this multimorbid syndrome.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>\n                      We studied 2151 patients with HF from the BIOSTAT\u2010CHF cohort. Patients were stratified based on ID (transferrin saturation &lt;20%), anaemia (World Health Organization definition) and\/or CKD (estimated glomerular filtration rate &lt;60\u2009ml\/min\/1.73\u2009m\n                      <jats:sup>2<\/jats:sup>\n                      ). Patients were mainly men (73.3%), with a median age of 70.5 (interquartile range 61.4\u201378.1). ID was more prevalent than CKD and anaemia (63.3%, 47.2% and 35.6% respectively), with highest prevalence in those with concomitant CKD and anaemia (77.5% vs. 59.3%;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001). There was a considerable overlap in biomarkers and pathways between patients with isolated ID, anaemia or CKD, or in combination, with processes related to immunity, inflammation, cell survival and cancer amongst the common pathways. Key biomarkers shared between syndromes with ID included transferrin receptor, interleukin\u20106, fibroblast growth factor\u201023, and bone morphogenetic protein 6. Having ID, either alone or on top of anaemia and\/or CKD, was associated with a lower overall summary Kansas City Cardiomyopathy Questionnaire score, an impaired 6\u2010min walk test and increased incidence of hospitalizations and\/or mortality in multivariable analyses (all\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Iron deficiency, CKD and\/or anaemia in patients with HF have great overlap in biomarker profiles, suggesting common pathways associated with these syndromes. ID either alone or on top of CKD and anaemia is associated with worse quality of life, exercise capacity and prognosis of patients with worsening HF.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ejhf.2393","type":"journal-article","created":{"date-parts":[[2021,11,24]],"date-time":"2021-11-24T01:55:30Z","timestamp":1637718930000},"page":"192-204","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":44,"title":["Additional burden of iron deficiency in heart failure patients beyond the cardio\u2010renal anaemia syndrome: findings from the\n                    <scp>BIOSTAT\u2010CHF<\/scp>\n                    study"],"prefix":"10.1093","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7012-9422","authenticated-orcid":false,"given":"Ridha I.S.","family":"Alnuwaysir","sequence":"first","affiliation":[{"name":"Department of Cardiology University Medical Center Groningen, University of Groningen  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 Medical Center Groningen, University of Groningen  Groningen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0234-438X","authenticated-orcid":false,"given":"Martijn F.","family":"Hoes","sequence":"additional","affiliation":[{"name":"Department of Cardiology University Medical Center Groningen, University of Groningen  Groningen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8192-6670","authenticated-orcid":false,"given":"George","family":"Markousis\u2010Mavrogenis","sequence":"additional","affiliation":[{"name":"Department of Cardiology University Medical Center Groningen, University of Groningen  Groningen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7317-8980","authenticated-orcid":false,"given":"Karla A.","family":"Gomez","sequence":"additional","affiliation":[{"name":"Department of Cardiology University Medical Center Groningen, University of Groningen  Groningen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haye H.","family":"van der Wal","sequence":"additional","affiliation":[{"name":"Department of Cardiology University Medical Center Groningen, University of Groningen  Groningen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1471-7016","authenticated-orcid":false,"given":"John G.F.","family":"Cleland","sequence":"additional","affiliation":[{"name":"Robertson Centre for Biostatistics, Institute of Health and Wellbeing University of Glasgow, Glasgow and National Heart &amp; Lung Institute, Imperial College  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth","family":"Dickstein","sequence":"additional","affiliation":[{"name":"University of Bergen, Stavanger University Hospital  Stavanger Norway"}],"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 &amp; 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, Glenfield Hospital  Leicester UK"},{"name":"NIHR Leicester Biomedical Research Centre Glenfield Hospital  Leicester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piotr","family":"Ponikowski","sequence":"additional","affiliation":[{"name":"Department of Heart Diseases Wroclaw Medical University, and Cardiology Department, Military Hospital  Wroclaw Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan D.","family":"Anker","sequence":"additional","affiliation":[{"name":"Department of Cardiology (CVK); and Berlin Institute of Health Center for Regenerative Therapies (BCRT); German Centre for Cardiovascular Research (DZHK) partner site Berlin Charit\u00e9 Universit\u00e4tsmedizin Berlin  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dirk J.","family":"van Veldhuisen","sequence":"additional","affiliation":[{"name":"Department of Cardiology University Medical Center Groningen, University of Groningen  Groningen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriaan A.","family":"Voors","sequence":"additional","affiliation":[{"name":"Department of Cardiology University Medical Center Groningen, University of Groningen  Groningen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"van der Meer","sequence":"additional","affiliation":[{"name":"Department of Cardiology University Medical Center Groningen, University of Groningen  Groningen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,12,9]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjmed.2014.08.024"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2008.04.061"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1159\/000243795"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cardfail.2004.03.003"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1159\/000443339"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000052622.51963.FC"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/ejhf.1154"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/ejhf.84"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2011.04.040"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/ejhf.1710"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0908355"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(20)32339-4"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehu385"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.117.027497"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehab368"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamacardio.2016.1161"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/ehf2.12351"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12872-017-0497-2"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurjhf\/hfs056"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.4061\/2011\/365301"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/ejhf.531"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/ejhf.785"},{"key":"e_1_2_6_24_1","doi-asserted-by":"crossref","DOI":"10.1161\/CIRCHEARTFAILURE.117.004519","article-title":"Definition of iron deficiency based on the gold standard of bone marrow iron staining in heart failure patients","volume":"11","author":"Beverborg NG","year":"2018","journal-title":"Circ Heart Fail"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10741-011-9283-x"},{"key":"e_1_2_6_26_1","first-page":"S1","article-title":"K\/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification","volume":"39","author":"National Kidney Foundation","year":"2002","journal-title":"Am J Kidney Dis"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehz680"},{"key":"e_1_2_6_28_1","unstructured":"Precision Proteomics Solutions for biomarker discovery | Olink[Internet]. 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