{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T00:07:33Z","timestamp":1781482053239,"version":"3.54.1"},"reference-count":37,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"16","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2019,8,20]]},"abstract":"<jats:sec xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              In patients with chronic heart failure and chronic kidney disease, correction of anemia with erythropoietin\u2010stimulating agents targeting normal hemoglobin levels is associated with an increased risk of cardiovascular morbidity and mortality. Emerging data suggest a direct effect of erythropoietin on fibroblast growth factor 23 (\n              <jats:styled-content style=\"fixed-case\">FGF<\/jats:styled-content>\n              23), elevated levels of which have been associated with adverse outcomes. We investigate effects of erythropoietin\u2010stimulating agents in patients with both chronic heart failure and chronic kidney disease focusing on\n              <jats:styled-content style=\"fixed-case\">FGF<\/jats:styled-content>\n              23.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Methods and Results<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              In the\n              <jats:styled-content style=\"fixed-case\">EPOCARES<\/jats:styled-content>\n              (Erythropoietin in CardioRenal Syndrome) study, we randomized 56 anemic patients (median age 74 [interquartile range 69\u201380] years, 66% male) with both chronic heart failure and chronic kidney disease into 3 groups, of which 2 received epoetin beta 50\u00a0\n              <jats:styled-content style=\"fixed-case\">IU<\/jats:styled-content>\n              \/kg per week for 50\u00a0weeks, and the third group served as control. Measurements were performed at baseline and after 2, 26, and 50\u00a0weeks. Data were analyzed using linear mixed\u2010model analysis. After 50\u00a0weeks of erythropoietin\u2010stimulating agent treatment, hematocrit and hemoglobin levels increased. Similarly, C\u2010terminal\n              <jats:styled-content style=\"fixed-case\">FGF<\/jats:styled-content>\n              23 levels, in contrast to intact\n              <jats:styled-content style=\"fixed-case\">FGF<\/jats:styled-content>\n              23 levels, rose significantly due to erythropoietin\u2010stimulating agents as compared with the controls. During median follow\u2010up for 5.7 (2.0\u20135.7) years, baseline C\u2010terminal\n              <jats:styled-content style=\"fixed-case\">FGF<\/jats:styled-content>\n              23 levels were independently associated with increased risk of mortality (hazard ratio 2.20; 95%\n              <jats:styled-content style=\"fixed-case\">CI<\/jats:styled-content>\n              , 1.35\u20103.59;\n              <jats:italic>P<\/jats:italic>\n              =0.002).\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              Exogenous erythropoietin increases C\u2010terminal\n              <jats:styled-content style=\"fixed-case\">FGF<\/jats:styled-content>\n              23 levels markedly over a period of 50\u00a0weeks, elevated levels of which, even at baseline, are significantly associated with an increased risk of mortality. The current results, in a randomized trial setting, underline the strong relationship between erythropoietin and\n              <jats:styled-content style=\"fixed-case\">FGF<\/jats:styled-content>\n              23 physiology in patients with chronic heart failure and chronic kidney disease.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Clinical Trial Registration<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              <jats:styled-content style=\"fixed-case\">URL<\/jats:styled-content>\n              :\n              <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/www.clinicaltrials.gov\">http:\/\/www.clinicaltrials.gov<\/jats:ext-link>\n              . Unique identifier:\n              <jats:styled-content style=\"fixed-case\">NCT<\/jats:styled-content>\n              00356733.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.118.011130","type":"journal-article","created":{"date-parts":[[2019,8,17]],"date-time":"2019-08-17T09:04:05Z","timestamp":1566032645000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":20,"title":["Epoetin Beta and C\u2010Terminal Fibroblast Growth Factor 23 in Patients With Chronic Heart Failure and Chronic Kidney Disease"],"prefix":"10.1161","volume":"8","author":[{"given":"Michele F.","family":"Eisenga","sequence":"first","affiliation":[{"name":"Division of Nephrology Department of Internal Medicine University of Groningen University Medical Center Groningen Groningen the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mireille E.","family":"Emans","sequence":"additional","affiliation":[{"name":"Department of Cardiology Ikazia Hospital Rotterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karien","family":"van der Putten","sequence":"additional","affiliation":[{"name":"Department of Nephrology Tergooi Hospital Hilversum the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maarten J.","family":"Cramer","sequence":"additional","affiliation":[{"name":"Department of Cardiology University of Utrecht University Medical Center Utrecht Utrecht the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adry","family":"Diepenbroek","sequence":"additional","affiliation":[{"name":"Division of Nephrology Department of Internal Medicine University of Groningen University Medical Center Groningen Groningen the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Birgitta K.","family":"Velthuis","sequence":"additional","affiliation":[{"name":"Department of Radiology University of Utrecht University Medical Center Utrecht Utrecht the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pieter A.","family":"Doevendans","sequence":"additional","affiliation":[{"name":"Department of Cardiology University of Utrecht University Medical Center Utrecht Utrecht the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marianne C.","family":"Verhaar","sequence":"additional","affiliation":[{"name":"Department of Nephrology and Hypertension University of Utrecht University Medical Center Utrecht Utrecht the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaap A.","family":"Joles","sequence":"additional","affiliation":[{"name":"Department of Nephrology and Hypertension University of Utrecht University Medical Center Utrecht Utrecht the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephan J. L.","family":"Bakker","sequence":"additional","affiliation":[{"name":"Division of Nephrology Department of Internal Medicine University of Groningen University Medical Center Groningen Groningen the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilja M.","family":"Nolte","sequence":"additional","affiliation":[{"name":"Department of Epidemiology University of Groningen University Medical Center Groningen Groningen the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Branko","family":"Braam","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Immunology Department of Medicine University of Alberta Edmonton Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlo A. J. 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