{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T18:09:49Z","timestamp":1789236589383,"version":"build-2803163510"},"reference-count":29,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2018,7,20]],"date-time":"2018-07-20T00:00:00Z","timestamp":1532044800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Stiftung Rheinland Pfalz","award":["AZ 15202\u2013386261\/545"],"award-info":[{"award-number":["AZ 15202\u2013386261\/545"]}]},{"DOI":"10.13039\/501100000780","name":"European Union","doi-asserted-by":"publisher","award":["HEALTH-F2-2011-278913"],"award-info":[{"award-number":["HEALTH-F2-2011-278913"]}],"id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010447","name":"DZHK","doi-asserted-by":"publisher","award":["81Z1710101"],"award-info":[{"award-number":["81Z1710101"]}],"id":[{"id":"10.13039\/100010447","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Acute myocardial infarction remains a leading cause of morbidity and mortality. While iron deficient heart failure patients are at increased risk of future cardiovascular events and see improvement with intravenous supplementation, the clinical relevance of iron deficiency in acute coronary syndrome remains unclear. We aimed to evaluate the prognostic value of iron deficiency in the acute coronary syndrome (ACS). Levels of ferritin, iron, and transferrin were measured at baseline in 836 patients with ACS. A total of 29.1% was categorized as iron deficient. The prevalence of iron deficiency was clearly higher in women (42.8%), and in patients with anemia (42.5%). During a median follow-up of 4.0 years, 111 subjects (13.3%) experienced non-fatal myocardial infarction (MI) and cardiovascular mortality as combined endpoint. Iron deficiency strongly predicted non-fatal MI and cardiovascular mortality with a hazard ratio (HR) of 1.52 (95% confidence interval (CI) 1.03-2.26; p = 0.037) adjusted for age, sex, hypertension, smoking status, diabetes, hyperlipidemia, body-mass-index (BMI) This association remained significant (HR 1.73 (95% CI 1.07\u20132.81; p = 0.026)) after an additional adjustment for surrogates of cardiac function and heart failure severity (N-terminal pro B-type natriuretic peptide, NT-proBNP), for the size of myocardial necrosis (troponin), and for anemia (hemoglobin). Survival analyses for cardiovascular mortality and MI provided further evidence for the prognostic relevance of iron deficiency (HR 1.50 (95% CI 1.02\u20132.20)). Our data showed that iron deficiency is strongly associated with adverse outcome in acute coronary syndrome.<\/jats:p>","DOI":"10.3390\/biom8030060","type":"journal-article","created":{"date-parts":[[2018,7,23]],"date-time":"2018-07-23T03:24:27Z","timestamp":1532316267000},"page":"60","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":56,"title":["Adverse Outcome Prediction of Iron Deficiency in Patients with Acute Coronary Syndrome"],"prefix":"10.3390","volume":"8","author":[{"given":"Tanja","family":"Zeller","sequence":"first","affiliation":[{"name":"Department of General and Interventional Cardiology, University Heart Center Hamburg, 20246 Hamburg, Germany"},{"name":"German Center for Cardiovascular Research (DZHK), Partner Site Hamburg, L\u00fcbeck, Kiel, 20246 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Waldeyer","sequence":"additional","affiliation":[{"name":"Department of General and Interventional Cardiology, University Heart Center Hamburg, 20246 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4037-144X","authenticated-orcid":false,"given":"Francisco","family":"Ojeda","sequence":"additional","affiliation":[{"name":"Department of General and Interventional Cardiology, University Heart Center Hamburg, 20246 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renate B.","family":"Schnabel","sequence":"additional","affiliation":[{"name":"Department of General and Interventional Cardiology, University Heart Center Hamburg, 20246 Hamburg, Germany"},{"name":"German Center for Cardiovascular Research (DZHK), Partner Site Hamburg, L\u00fcbeck, Kiel, 20246 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarina","family":"Sch\u00e4fer","sequence":"additional","affiliation":[{"name":"Department of General and Interventional Cardiology, University Heart Center Hamburg, 20246 Hamburg, Germany"},{"name":"German Center for Cardiovascular Research (DZHK), Partner Site Hamburg, L\u00fcbeck, Kiel, 20246 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alev","family":"Altay","sequence":"additional","affiliation":[{"name":"Department of General and Interventional Cardiology, University Heart Center Hamburg, 20246 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karl J.","family":"Lackner","sequence":"additional","affiliation":[{"name":"German Center for Cardiovascular Research (DZHK), Partner Site Hamburg, L\u00fcbeck, Kiel, 20246 Hamburg, Germany"},{"name":"Department of Laboratory Medicine, University Medical Center, Johannes Gutenberg University Mainz, 55131 Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan D.","family":"Anker","sequence":"additional","affiliation":[{"name":"German Center for Cardiovascular Research (DZHK), Partner Site Hamburg, L\u00fcbeck, Kiel, 20246 Hamburg, Germany"},{"name":"Department of Cardiology (CVK) and Berlin-Brandenburg Center for Regenerative Therapies (BCRT), 13353 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dirk","family":"Westermann","sequence":"additional","affiliation":[{"name":"Department of General and Interventional Cardiology, University Heart Center Hamburg, 20246 Hamburg, Germany"},{"name":"German Center for Cardiovascular Research (DZHK), Partner Site Hamburg, L\u00fcbeck, Kiel, 20246 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Blankenberg","sequence":"additional","affiliation":[{"name":"Department of General and Interventional Cardiology, University Heart Center Hamburg, 20246 Hamburg, Germany"},{"name":"German Center for Cardiovascular Research (DZHK), Partner Site Hamburg, L\u00fcbeck, Kiel, 20246 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahir","family":"Karakas","sequence":"additional","affiliation":[{"name":"Department of General and Interventional Cardiology, University Heart Center Hamburg, 20246 Hamburg, Germany"},{"name":"German Center for Cardiovascular Research (DZHK), Partner Site Hamburg, L\u00fcbeck, Kiel, 20246 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2018,7,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3241","DOI":"10.1007\/s00018-009-0051-1","article-title":"Mammalian iron transport","volume":"66","author":"Anderson","year":"2009","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1986","DOI":"10.1056\/NEJM199912233412607","article-title":"Disorders of iron metabolism","volume":"341","author":"Andrews","year":"1999","journal-title":"N. Engl. J. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"816","DOI":"10.1093\/eurheartj\/ehs224","article-title":"Iron deficiency and heart failure: Diagnostic dilemmas and therapeutic perspectives","volume":"34","author":"Jankowska","year":"2013","journal-title":"Eur. Heart J."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Zeller, T., Altay, A., Waldeyer, C., Appelbaum, S., Ojeda, F., Ruhe, J., Schnabel, R.B., Lackner, K.J., Blankenberg, S., and Karakas, M. (2018). Prognostic Value of Iron-Homeostasis Regulating Peptide Hepcidin in Coronary Heart Disease\u2014Evidence from the Large AtheroGene Study. Biomolecules, 8.","DOI":"10.3390\/biom8030043"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Traghella, I., Mastorci, F., Alessia, P., Pingitore, A., and Vassalle, C. (2018). Nontraditional Cardiovascular Biomarkers and Risk Factors: Rationale and Future Perspectives. Biomolecules, 8.","DOI":"10.3390\/biom8020040"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"S4","DOI":"10.2215\/CJN.01490506","article-title":"Assessing iron status: Beyond serum ferritin and transferrin saturation","volume":"1","author":"Wish","year":"2006","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"4754","DOI":"10.1182\/blood-2010-05-286260","article-title":"Detection, evaluation, and management of iron-restricted erythropoiesis","volume":"116","author":"Goodnough","year":"2010","journal-title":"Blood"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"525","DOI":"10.5694\/j.1326-5377.2010.tb04038.x","article-title":"Diagnosis and management of iron deficiency anaemia: A clinical update","volume":"193","author":"Pasricha","year":"2010","journal-title":"Med. J. Aust."},{"key":"ref_9","unstructured":"Schaefer, S., Zeller, T., Waldeyer, C., Ojeda, F., Schnabel, R., Atay, A., Lackner, K., Anker, S., Westermann, D., and Blankenberg, S. (2017). 5759 Iron deficiency independently and strongly predicts adverse outcome in patients with acute coronary syndrome\u2014First report on the prospective relevance of iron deficiency. Eur. Heart J., 38."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2436","DOI":"10.1056\/NEJMoa0908355","article-title":"Ferric carboxymaltose in patients with heart failure and iron deficiency","volume":"361","author":"Anker","year":"2009","journal-title":"N. Engl. J. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1093\/eurheartj\/ehu385","article-title":"Beneficial effects of long-term intravenous iron therapy with ferric carboxymaltose in patients with symptomatic heart failure and iron deficiency","volume":"36","author":"Ponikowski","year":"2015","journal-title":"Eur. Heart J."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Jankowska, E.A., Tkaczyszyn, M., Suchocki, T., Drozd, M., von Haehling, S., Doehner, W., Banasiak, W., Filippatos, G., Anker, S.D., and Ponikowski, P. (2016). Effects of intravenous iron therapy in iron-deficient patients with systolic heart failure: A meta-analysis of randomized controlled trials. Eur. J. Heart Fail.","DOI":"10.1002\/ejhf.473"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1605","DOI":"10.1056\/NEJMoa030535","article-title":"Glutathione peroxidase 1 activity and cardiovascular events in patients with coronary artery disease","volume":"349","author":"Blankenberg","year":"2003","journal-title":"N. Engl. J. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1093\/eurheartj\/ehn009","article-title":"Association of adiponectin with adverse outcome in coronary artery disease patients: Results from the AtheroGene study","volume":"29","author":"Schnabel","year":"2008","journal-title":"Eur. Heart J."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1001\/jama.1995.03520260058033","article-title":"Risk stratification in unstable angina: Prospective validation of the Braunwald classification","volume":"273","author":"Calvin","year":"1995","journal-title":"J. Am. Med. Assoc."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1016\/j.ijcard.2014.10.006","article-title":"Bone marrow iron depletion is common in patients with coronary artery disease","volume":"182","author":"Jankowska","year":"2015","journal-title":"Int. J. Cardiol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1872","DOI":"10.1093\/eurheartj\/ehq158","article-title":"Iron deficiency: An ominous sign in patients with systolic chronic heart failure","volume":"31","author":"Jankowska","year":"2010","journal-title":"Eur. Heart J."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1038\/nrcardio.2015.109","article-title":"Iron deficiency and cardiovascular disease","volume":"12","author":"Jankowska","year":"2015","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1016\/j.atherosclerosis.2014.07.002","article-title":"Hemoglobin, iron metabolism and angiographic coronary artery disease (The Ludwigshafen Risk and Cardiovascular Health Study)","volume":"236","author":"Grammer","year":"2014","journal-title":"Atherosclerosis"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"3969","DOI":"10.3892\/mmr.2016.5705","article-title":"Influence of the availability of iron during hypoxia on the genes associated with apoptotic activity and local iron metabolism in rat H9C2 cardiomyocytes and L6G8C5 skeletal myocytes","volume":"14","author":"Dziegala","year":"2016","journal-title":"Mol. Med. Rep."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1016\/j.jnutbio.2009.04.009","article-title":"Expression of the peptide hormone hepcidin increases in cardiomyocytes under myocarditis and myocardial infarction","volume":"21","author":"Isoda","year":"2010","journal-title":"J. Nutr. Biochem."},{"key":"ref_22","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":"ref_23","doi-asserted-by":"crossref","first-page":"1786","DOI":"10.1016\/j.peptides.2010.05.013","article-title":"The iron-regulatory peptide hepcidin is upregulated in the ischemic and in the remote myocardium after myocardial infarction","volume":"31","author":"Simonis","year":"2010","journal-title":"Peptides"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1319","DOI":"10.3390\/biom5031319","article-title":"High-Resolution Respirometry for Simultaneous Measurement of Oxygen and Hydrogen Peroxide Fluxes in Permeabilized Cells, Tissue Homogenate and Isolated Mitochondria","volume":"5","author":"Krumschnabel","year":"2015","journal-title":"Biomolecules"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Alayash, A.I. (2017). Hemoglobin-Based Blood Substitutes and the Treatment of Sickle Cell Disease: More Harm than Help?. Biomolecules, 7.","DOI":"10.3390\/biom7010002"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1016\/j.ijcard.2014.02.016","article-title":"Positive effect of intravenous iron-oxide administration on left ventricular remodelling in patients with acute ST-elevation myocardial infarction\u2014A cardiovascular magnetic resonance (CMR) study","volume":"173","author":"Florian","year":"2014","journal-title":"Int. J. Cardiol."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Haddad, S., Wang, Y., Galy, B., Korf-Klingebiel, M., Hirsch, V., Baru, A.M., Rostami, F., Reboll, M.R., Heineke, J., and Groos, U.F.S. (2016). Iron-regulatory proteins secure iron availability in cardiomyocytes to prevent heart failure. Eur. Heart J.","DOI":"10.1093\/eurheartj\/ehw333"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1016\/j.jneuroim.2005.11.011","article-title":"Cytokine profile of iron-laden macrophages: Implications for cellular magnetic resonance imaging","volume":"173","author":"Siglienti","year":"2006","journal-title":"J. Neuroimmunol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1161\/CIR.0000000000000366","article-title":"Executive Summary: Heart Disease and Stroke Statistics-2016 Update: A report from the American Heart Association","volume":"133","author":"Mozaffarian","year":"2016","journal-title":"Circulation"}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/8\/3\/60\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T15:13:25Z","timestamp":1760195605000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/8\/3\/60"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,7,20]]},"references-count":29,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2018,9]]}},"alternative-id":["biom8030060"],"URL":"https:\/\/doi.org\/10.3390\/biom8030060","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,7,20]]}}}