{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T19:53:39Z","timestamp":1791575619923,"version":"4.3.4"},"reference-count":46,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2020,8,21]],"date-time":"2020-08-21T00:00:00Z","timestamp":1597968000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100011105","name":"Fourth Framework Programme","doi-asserted-by":"publisher","award":["FP7-242209-BIOSTAT-CHF"],"award-info":[{"award-number":["FP7-242209-BIOSTAT-CHF"]}],"id":[{"id":"10.13039\/100011105","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Selenium is an essential micronutrient, and a low selenium concentration (&lt;100 \u00b5g\/L) is associated with a poorer quality of life and exercise capacity, and an impaired prognosis in patients with worsening heart failure. Measuring selenium concentrations routinely is laborious and costly, and although its clinical utility is yet to be proven, an easy implemented model to predict selenium status is desirable. A stepwise multivariable logistic regression analysis was performed using routinely measured clinical factors. Low selenium was independently predicted by: older age, lower serum albumin, higher N-terminal pro-B-type natriuretic peptide levels, worse kidney function, and the presence of orthopnea and iron deficiency. A 10-points risk-model was developed, and a score of \u22656 points identified &gt;80% of patients with low selenium (sensitivity of 44%, specificity of 80%). Given that selenium and iron overlap in their physiological roles, we evaluated the shared determinants and prognostic associates. Both deficiencies shared similar clinical characteristics, including the model risk factors and, in addition, a low protein intake and high levels of C-reactive protein. Low selenium was associated with a similar or worse prognosis compared to iron deficiency. In conclusion, although it is difficult to exclude low selenium based on clinical characteristics alone, we provide a prediction tool which identifies heart failure patients at higher risk of having a low selenium status.<\/jats:p>","DOI":"10.3390\/nu12092541","type":"journal-article","created":{"date-parts":[[2020,8,21]],"date-time":"2020-08-21T09:21:51Z","timestamp":1598001711000},"page":"2541","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["A Clinical Tool to Predict Low Serum Selenium in Patients with Worsening Heart Failure"],"prefix":"10.3390","volume":"12","author":[{"given":"Ali A.","family":"Al-Mubarak","sequence":"first","affiliation":[{"name":"Department of Cardiology, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niels","family":"Grote Beverborg","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan D.","family":"Anker","sequence":"additional","affiliation":[{"name":"Innovative Clinical Trials, Department of Cardiology and Pneumology, University Medical Centre G\u00f6ttingen (UMG), 37075 G\u00f6ttingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nilesh J.","family":"Samani","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Sciences, University of Leicester, Leicester LE39QP, UK"},{"name":"NIHR Leicester Biomedical Research Centre, Glenfield Hospital, Leicester LE39QP, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth","family":"Dickstein","sequence":"additional","affiliation":[{"name":"Stavanger University Hospital, 4011 Stavanger, Norway"},{"name":"Department of Clinical Science, University of Bergen, 5007 Bergen, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerasimos","family":"Filippatos","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Heart Failure Unit, Athens University Hospital Attikon, 124 06 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dirk Jan","family":"van Veldhuisen","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University Medical Center Groningen, University of Groningen, 9700 RB 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, 9700 RB Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5926-6960","authenticated-orcid":false,"given":"Nils","family":"Bomer","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University Medical Center Groningen, University of Groningen, 9700 RB 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, 9700 RB Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,8,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1002\/ejhf.592","article-title":"2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC). Developed with the special contribution","volume":"18","author":"Ponikowski","year":"2016","journal-title":"Eur. J. Heart Fail."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1161\/JAHA.118.010447","article-title":"Nutrient deficiencies in heart failure: A micro problem with macro effects?","volume":"7","author":"Cascino","year":"2018","journal-title":"J. Am. Heart Assoc."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1756","DOI":"10.1056\/NEJMcibr1402199","article-title":"Keshan Disease, Selenium Deficiency, and the Selenoproteome","volume":"370","author":"Loscalzo","year":"2014","journal-title":"N. Engl. J. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1016\/j.cardfail.2018.02.011","article-title":"Association of Serum Zinc Level with Prognosis in Patients With Heart Failure","volume":"24","author":"Yoshihisa","year":"2018","journal-title":"J. Card. Fail."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1097\/JCN.0000000000000322","article-title":"Dietary Micronutrient Intake and Micronutrient Status in Patients With Chronic Stable Heart Failure","volume":"32","author":"McKeag","year":"2017","journal-title":"J. Cardiovasc. Nurs."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1161\/JAHA.117.007251","article-title":"Micronutrient deficiency independently predicts time to event in patients with heart failure","volume":"7","author":"Lennie","year":"2018","journal-title":"J. Am. Heart Assoc."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1001\/jamacardio.2019.1739","article-title":"Differences in Clinical Profile and Outcomes of Low Iron Storage vs Defective Iron Utilization in Patients with Heart Failure: Results from the DEFINE-HF and BIOSTAT-CHF Studies","volume":"4","author":"Klip","year":"2019","journal-title":"JAMA Cardiol."},{"key":"ref_8","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":"ref_9","doi-asserted-by":"crossref","first-page":"3616","DOI":"10.1093\/eurheartj\/ehz680","article-title":"Iron deficiency in worsening heart failure is associated with reduced estimated protein intake, fluid retention, inflammation, and antiplatelet use","volume":"40","author":"Dickstein","year":"2019","journal-title":"Eur. Heart J."},{"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":"1374","DOI":"10.1161\/CIRCULATIONAHA.117.027497","article-title":"Effect of Ferric Carboxymaltose on Exercise Capacity in Patients With Chronic Heart Failure and Iron Deficiency","volume":"136","author":"Ponikowski","year":"2017","journal-title":"Circulation"},{"key":"ref_12","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\u2020","volume":"36","author":"Ponikowski","year":"2014","journal-title":"Eur. Heart J."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1651","DOI":"10.1002\/ejhf.1710","article-title":"Rationale and design of the AFFIRM-AHF trial: A randomised, double-blind, placebo-controlled trial comparing the effect of intravenous ferric carboxymaltose on hospitalisations and mortality in iron-deficient patients admitted for acute heart failure","volume":"21","author":"Ponikowski","year":"2019","journal-title":"Eur. J. Heart Fail."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1007\/s12011-018-1302-5","article-title":"Prevention of Keshan Disease by Selenium Supplementation: A Systematic Review and Meta-analysis","volume":"186","author":"Zhou","year":"2018","journal-title":"Biol. Trace Elem. Res."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Bomer, N., Grote Beverborg, N., Hoes, M.F., Streng, K.W., Vermeer, M., Dokter, M.M., IJmker, J., Anker, S.D., Cleland, J.G.F., and Hillege, H.L. (2019). Selenium and outcome in heart failure. Eur. J. Heart Fail., 1\u20139.","DOI":"10.1002\/ejhf.1644"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1016\/j.ahj.2004.12.010","article-title":"Monitoring clinical changes in patients with heart failure: A comparison of methods","volume":"150","author":"Spertus","year":"2005","journal-title":"Am. Heart J."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1161\/CIRCOUTCOMES.115.001958","article-title":"Development and Validation of a Short Version of the Kansas City Cardiomyopathy Questionnaire","volume":"8","author":"Spertus","year":"2015","journal-title":"Circ. Cardiovasc. Qual. Outcomes"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/j.critrevonc.2015.05.010","article-title":"Functional role of inorganic trace elements in angiogenesis-Part I: N, Fe, Se, P, Au, and Ca","volume":"96","author":"Saghiri","year":"2015","journal-title":"Crit. Rev. Oncol. Hematol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"716","DOI":"10.1002\/ejhf.531","article-title":"A systems BIOlogy Study to TAilored Treatment in Chronic Heart Failure: Rationale, design, and baseline characteristics of BIOSTAT-CHF","volume":"18","author":"Voors","year":"2016","journal-title":"Eur. J. Heart Fail."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1002\/ejhf.785","article-title":"Development and validation of multivariable models to predict mortality and hospitalization in patients with heart failure","volume":"19","author":"Voors","year":"2017","journal-title":"Eur. J. Heart Fail."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"e004519","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":"Klip","year":"2018","journal-title":"Circ. Heart Fail."},{"key":"ref_22","unstructured":"Hair, J.F., Black, W.C., Babin, B.J., and Anderson, R.E. (1998). Multivariate Data Analysis, Prentice-Hall."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1145\/1656274.1656278","article-title":"The WEKA data mining software","volume":"11","author":"Hall","year":"2009","journal-title":"ACM Sigkdd Explor. Newsl."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Lewandowska, M., Wi\u0119ckowska, B., Sajdak, S., and Lubi\u0144ski, J. (2020). First Trimester Microelements and Their Relationships with Pregnancy Outcomes and Complications. Nutrients, 12.","DOI":"10.3390\/nu12041108"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1079\/BJN20051528","article-title":"Serum selenium determinants in French adults: The SU.VI.M.AX study","volume":"95","author":"Arnaud","year":"2006","journal-title":"Br. J. Nutr."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e34","DOI":"10.1056\/NEJMoa1800389","article-title":"Primary Prevention of Cardiovascular Disease with a Mediterranean Diet Supplemented with Extra-Virgin Olive Oil or Nuts","volume":"378","author":"Estruch","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1001\/archinternmed.2007.74","article-title":"Serum selenium levels and all-cause, cancer, and cardiovascular mortality among US adults","volume":"168","author":"Bleys","year":"2008","journal-title":"Arch. Intern. Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1038\/ejcn.2015.78","article-title":"Selenium status and cardiovascular diseases: Meta-analysis of prospective observational studies and randomized controlled trials","volume":"70","author":"Zhang","year":"2016","journal-title":"Eur. J. Clin. Nutr."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1136\/bmj.314.7078.387","article-title":"Dietary selenium: Time to act","volume":"314","author":"Rayman","year":"1997","journal-title":"BMJ"},{"key":"ref_30","first-page":"363","article-title":"New Approaches to Assess Selenium Status and Requirement","volume":"58","year":"2000","journal-title":"Nutr. Rev."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1079\/BJN19930057","article-title":"Long-term supplementation with selenate and selenomethionine: Selenium and glutathione peroxidase (EC 1.11.1.9) in blood components of New Zealand women","volume":"69","author":"Thomson","year":"1993","journal-title":"Br. J. Nutr."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1007\/s42000-019-00150-4","article-title":"The other view: The trace element selenium as a micronutrient in thyroid disease, diabetes, and beyond","volume":"19","author":"Schomburg","year":"2020","journal-title":"Hormones"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Schomburg, L., Orho-Melander, M., Struck, J., Bergmann, A., and Melander, O. (2019). Selenoprotein-P Deficiency Predicts Cardiovascular Disease and Death. Nutrients, 11.","DOI":"10.3390\/nu11081852"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"357","DOI":"10.4162\/nrp.2011.5.4.357","article-title":"Demographic and lifestyle factors and selenium levels in men and women in the U.S","volume":"5","author":"Park","year":"2011","journal-title":"Nutr. Res. Pract."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1038\/ejcn.2015.92","article-title":"Relatively high mortality risk in elderly Swedish subjects with low selenium status","volume":"70","author":"Alehagen","year":"2016","journal-title":"Eur. J. Clin. Nutr."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1007\/s11897-017-0370-8","article-title":"Visceral Congestion in Heart Failure: Right Ventricular Dysfunction, Splanchnic Hemodynamics, and the Intestinal Microenvironment","volume":"14","author":"Polsinelli","year":"2017","journal-title":"Curr. Heart Fail. Rep."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1035","DOI":"10.1007\/s40520-018-1086-7","article-title":"Selenium, aging and aging-related diseases","volume":"31","author":"Cai","year":"2019","journal-title":"Aging Clin. Exp. Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1860","DOI":"10.1016\/j.ijcard.2012.04.156","article-title":"Cardiovascular mortality and N-terminal-proBNP reduced after combined selenium and coenzyme Q10 supplementation: A 5-year prospective randomized double-blind placebo-controlled trial among elderly Swedish citizens","volume":"167","author":"Alehagen","year":"2013","journal-title":"Int. J. Cardiol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1159\/000323538","article-title":"Serum Selenium Levels in Hemodialysis Patients Are Significantly Lower than Those in Healthy Controls","volume":"32","author":"Yosuke","year":"2011","journal-title":"Blood Purif."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1080\/00365513.2016.1201852","article-title":"Variation of trace element concentrations in patients undergoing hemodialysis in the north of Spain","volume":"76","author":"Merayo","year":"2016","journal-title":"Scand. J. Clin. Lab. Investig."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Lai, H., Nie, T., Zhang, Y., Chen, Y., Tao, J., Lin, T., Ge, T., Li, F., and Li, H. (2020). Selenium Deficiency-Induced Damage and Altered Expression of Mitochondrial Biogenesis Markers in the Kidneys of Mice. Biol. Trace Elem. Res.","DOI":"10.1007\/s12011-020-02112-z"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1016\/j.clnu.2015.02.010","article-title":"The effect of the systemic inflammatory response on plasma zinc and selenium adjusted for albumin","volume":"35","author":"Ghashut","year":"2016","journal-title":"Clin. Nutr."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0946-672X(02)80002-5","article-title":"Selenium status and its correlates in a British National Diet and Nutrition Survey: People aged 65 years and over","volume":"16","author":"Bates","year":"2002","journal-title":"J. Trace Elem. Med. Biol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1","DOI":"10.4025\/actascianimsci.v41i1.44392","article-title":"Effects of different sources of selenium supplementation on antioxidant indices, biochemical parameters, thyroid hormones and se status in transition cows","volume":"41","author":"Khalili","year":"2019","journal-title":"Acta Sci. Anim. Sci."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1385\/BTER:111:1:23","article-title":"Serum and hair levels of zinc, selenium, iron, and copper in children with iron-deficiency anemia","volume":"111","year":"2006","journal-title":"Biol. Trace Elem. Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1385\/BTER:111:1:1","article-title":"Serum levels of trace elements and iron-deficiency anemia in adult Vietnamese","volume":"111","author":"Khan","year":"2006","journal-title":"Biol. Trace Elem. Res."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/12\/9\/2541\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:04:55Z","timestamp":1760177095000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/12\/9\/2541"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,8,21]]},"references-count":46,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2020,9]]}},"alternative-id":["nu12092541"],"URL":"https:\/\/doi.org\/10.3390\/nu12092541","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,8,21]]}}}