title: Potential Predictors of Plasma Fibroblast Growth Factor 23 Concentrations: Cross-Sectional Analysis in the EPIC-Germany Study.
abstract: BACKGROUND
  Increased fibroblast growth factor 23 (FGF23), a bone-derived hormone involved in the regulation of phosphate and vitamin D metabolism, has been related to the development of cardiovascular disease (CVD) in chronic kidney disease patients and in the general population. However, what determines higher FGF23 levels is still unclear. Also, little is known about the influence of diet on FGF23. The aim of this study was therefore to identify demographic, clinical and dietary correlates of high FGF23 concentrations in the general population.
  
  
  METHODS
  We performed a cross-sectional analysis within a randomly selected subcohort of the European Prospective Investigation into Cancer and Nutrition (EPIC)-Germany comprising 2134 middle-aged men and women. The Human FGF23 (C-Terminal) ELISA kit was used to measure FGF23 in citrate plasma. Dietary data were obtained at baseline via validated food frequency questionnaires including up to 148 food items.
  
  
  RESULTS
  Multivariable adjusted logistic regression showed that men had a 66% lower and smokers a 64% higher probability of having higher FGF23 (≥ 90 RU/mL) levels compared, respectively, with women and nonsmokers. Each doubling in parathyroid hormone, creatinine, and C-reactive protein was related to higher FGF23. Among the dietary factors, each doubling in calcium and total energy intake was related, respectively, to a 1.75 and to a 4.41 fold increased probability of having higher FGF23. Finally, each doubling in the intake of iron was related to an 82% lower probability of having higher FGF23 levels. Results did not substantially change after exclusion of participants with lower kidney function.
  
  
  CONCLUSIONS
  In middle-aged men and women traditional and non-traditional CVD risk factors were related to higher FGF23 concentrations. These findings may contribute to the understanding of the potential mechanisms linking increased FGF23 to increased CVD risk.
authors.affiliation: Research Group Cardiovascular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbrücke, Nuthetal, Germany; German Centre for Cardiovascular Research (DZHK), Partner Site Berlin, Berlin, Germany.
authors.forename: Romina
authors.initials: R
authors.lastname: di Giuseppe
authors.affiliation: Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Tilman
authors.initials: T
authors.lastname: Kühn
authors.affiliation: Institute of Agricultural and Nutritional Sciences, Human Nutrition Group, Martin Luther University Halle-Wittenberg, Halle (Saale), Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Hirche
authors.affiliation: Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbrücke, Nuthetal, Germany.
authors.forename: Brian
authors.initials: B
authors.lastname: Buijsse
authors.affiliation: Department of Clinical Medicine, University of Bergen, Bergen, Norway.
authors.forename: Jutta
authors.initials: J
authors.lastname: Dierkes
authors.affiliation: Department of Internal Medicine IV, University of Tübingen, Tübingen, Germany; German Center for Diabetes Research (DZD e.V.), Neuherberg, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Fritsche
authors.affiliation: Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Rudolf
authors.initials: R
authors.lastname: Kaaks
authors.affiliation: Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbrücke, Nuthetal, Germany.
authors.forename: Heiner
authors.initials: H
authors.lastname: Boeing
authors.affiliation: Institute of Agricultural and Nutritional Sciences, Human Nutrition Group, Martin Luther University Halle-Wittenberg, Halle (Saale), Germany.
authors.forename: Gabriele I
authors.initials: GI
authors.lastname: Stangl
authors.affiliation: Research Group Cardiovascular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbrücke, Nuthetal, Germany; Institute for Social Medicine, Epidemiology and Health Economics, Charité University Medical Center, Berlin, Germany; German Centre for Cardiovascular Research (DZHK), Partner Site Berlin, Berlin, Germany.
authors.forename: Cornelia
authors.initials: C
authors.lastname: Weikert
mesh_terms: D000328:Adult; D000368:Aged; D002097:C-Reactive Protein / Q000032:analysis; D002136:Calcium, Dietary / Q000032:analysis; D002318:Cardiovascular Diseases / Q000097:blood* / Q000175:diagnosis; D003404:Creatinine / Q000097:blood; D003430:Cross-Sectional Studies; D005260:Female; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000097:blood*; D005858:Germany; D006801:Humans; D019266:Iron, Dietary / Q000032:analysis; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D010281:Parathyroid Hormone / Q000097:blood; D010758:Phosphorus / Q000097:blood; D011237:Predictive Value of Tests; D011379:Prognosis; D011446:Prospective Studies; D051436:Renal Insufficiency, Chronic / Q000097:blood* / Q000175:diagnosis; D012307:Risk Factors; D012737:Sex Factors; D012907:Smoking
chemical_list: D002136:Calcium, Dietary; C000717427:FGF23 protein, human; D019266:Iron, Dietary; D010281:Parathyroid Hormone; D010758:Phosphorus; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23; D002097:C-Reactive Protein; D003404:Creatinine