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Institute","doi-asserted-by":"publisher","award":["U01HL130114"],"award-info":[{"award-number":["U01HL130114"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["R01AG023629"],"award-info":[{"award-number":["R01AG023629"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Context<\/jats:title>\n                  <jats:p>Higher fibroblast growth factor-23 (FGF23) concentrations are associated with heart failure and mortality in diverse populations, but the strengths of associations differ markedly depending up on which assay is used.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>We sought to evaluate whether iron deficiency, inflammation, or kidney function account for differences in the strengths of associations between these 2 FGF23 assays with clinical outcomes.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Design<\/jats:title>\n                  <jats:p>Case cohort study from the Cardiovascular Health Study.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Setting<\/jats:title>\n                  <jats:p>A total of 844 community-dwelling individuals aged 65 years or older with and without chronic kidney disease were followed for 10 years.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Outcomes<\/jats:title>\n                  <jats:p>Outcomes included death, incident heart failure (HF), and incident myocardial infarction (MI). Exposure was baseline intact and C-terminal FGF23. Using modified Cox models, adjusting sequentially we tested whether observed associations of each assay with outcomes were attenuated by iron status, inflammation, kidney function, or their combinations.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>FGF23 measured by either assay was associated with mortality in unadjusted analysis (intact FGF23 hazard ratio [HR] per 2-fold higher 1.45; 95% CI, 1.25-1.68; C-terminal FGF23 HR 1.38; 95% CI, 1.26-1.50). Adjustment for kidney function completely attenuated associations of intact FGF23 with mortality (HR 1.00; 95% CI, 0.85-1.17), but had much less influence on the association of C-terminal FGF23, for which results remained significant after adjustment (HR 1.15; 95% CI, 1.04-1.28). Attenuation was much less with adjustment for iron status or inflammation. Results were similar for the HF end point. Neither C-terminal or intact FGF23 was associated with MI risk.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>The relationship of FGF23 with clinical end points is markedly different depending on the type of FGF23 assay used. The associations of biologically active FGF23 with clinical end points may be confounded by kidney disease, and thus much weaker than previously thought.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1210\/clinem\/dgaa665","type":"journal-article","created":{"date-parts":[[2020,9,20]],"date-time":"2020-09-20T12:24:25Z","timestamp":1600604665000},"page":"e4875-e4885","source":"Crossref","is-referenced-by-count":26,"title":["Intact and C-Terminal FGF23 Assays\u2014Do Kidney Function, Inflammation, and Low Iron Influence Relationships With Outcomes?"],"prefix":"10.1210","volume":"105","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9011-0163","authenticated-orcid":false,"given":"Shilpa","family":"Sharma","sequence":"first","affiliation":[{"name":"Division of Nephrology, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California"},{"name":"Nephrology Section, Veteran Affairs Greater Los Angeles Healthcare System, Los Angeles, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronit","family":"Katz","sequence":"additional","affiliation":[{"name":"University of Washington, Seattle, Washington"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander L","family":"Bullen","sequence":"additional","affiliation":[{"name":"Division of Nephrology-Hypertension, Department of Medicine, University of California San Diego, San Diego, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paulo H M","family":"Chaves","sequence":"additional","affiliation":[{"name":"Benjamin Leon Center for Geriatric Research and Education, Department of Translational Medicine, Herbert Wertheim College of Medicine, Florida International University, Miami, Florida"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter W","family":"de Leeuw","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and CARIM School for Cardiovascular Diseases, Maastricht University Medical Centre, MD Maastricht, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abraham A","family":"Kroon","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and CARIM School for Cardiovascular Diseases, Maastricht University Medical Centre, MD Maastricht, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfons J H M","family":"Houben","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and CARIM School for Cardiovascular Diseases, Maastricht University Medical Centre, MD Maastricht, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael G","family":"Shlipak","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of California San Francisco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joachim H","family":"Ix","sequence":"additional","affiliation":[{"name":"Division of Nephrology-Hypertension, Department of Medicine, University of California San Diego, San Diego, California"},{"name":"Nephrology Section, Veterans Affairs San Diego Healthcare System, La Jolla, California"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2020,9,19]]},"reference":[{"issue":"11","key":"2021122106315922400_CIT0001","doi-asserted-by":"crossref","first-page":"4393","DOI":"10.1172\/JCI46122","article-title":"FGF23 induces left ventricular hypertrophy","volume":"121","author":"Faul","year":"2011","journal-title":"J Clin Invest."},{"issue":"3","key":"2021122106315922400_CIT0002","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1016\/j.jacc.2012.03.040","article-title":"Fibroblast growth factor-23 and death, heart failure, and cardiovascular events in community-living individuals: CHS (Cardiovascular Health Study)","volume":"60","author":"Ix","year":"2012","journal-title":"J Am Coll Cardiol."},{"issue":"3","key":"2021122106315922400_CIT0003","doi-asserted-by":"crossref","first-page":"e000936","DOI":"10.1161\/JAHA.114.000936","article-title":"Fibroblast growth factor-23 and incident coronary heart disease, heart failure, and cardiovascular mortality: the Atherosclerosis Risk in Communities study","volume":"3","author":"Lutsey","year":"2014","journal-title":"J Am Heart Assoc."},{"issue":"6","key":"2021122106315922400_CIT0004","doi-asserted-by":"crossref","first-page":"1096","DOI":"10.1681\/ASN.2018101058","article-title":"Effects of nicotinamide and lanthanum carbonate on serum phosphate and fibroblast growth factor-23 in CKD: the COMBINE trial","volume":"30","author":"Ix","year":"2019","journal-title":"J Am Soc Nephrol."},{"issue":"2","key":"2021122106315922400_CIT0005","doi-asserted-by":"crossref","first-page":"e024382","DOI":"10.1136\/bmjopen-2018-024382","article-title":"Can we IMPROVE cardiovascular outcomes through phosphate lowering in CKD? 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