Potential Predictors of Plasma Fibroblast Growth Factor 23 Concentrations: Cross-Sectional Analysis in the EPIC-Germany Study

PLoS One. 2015 Jul 20;10(7):e0133580. doi: 10.1371/journal.pone.0133580. eCollection 2015.

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.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • C-Reactive Protein / analysis
  • Calcium, Dietary / analysis
  • Cardiovascular Diseases / blood*
  • Cardiovascular Diseases / diagnosis
  • Creatinine / blood
  • Cross-Sectional Studies
  • Female
  • Fibroblast Growth Factor-23
  • Fibroblast Growth Factors / blood*
  • Germany
  • Humans
  • Iron, Dietary / analysis
  • Linear Models
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Parathyroid Hormone / blood
  • Phosphorus / blood
  • Predictive Value of Tests
  • Prognosis
  • Prospective Studies
  • Renal Insufficiency, Chronic / blood*
  • Renal Insufficiency, Chronic / diagnosis
  • Risk Factors
  • Sex Factors
  • Smoking

Substances

  • Calcium, Dietary
  • FGF23 protein, human
  • Iron, Dietary
  • Parathyroid Hormone
  • Phosphorus
  • Fibroblast Growth Factors
  • Fibroblast Growth Factor-23
  • C-Reactive Protein
  • Creatinine

Grants and funding

This work was supported by a grant from the German Heart Research Foundation (http://www.dshf.de/forschung_en.php). Measurements of PTH and 25(OH)D3 in the subcohort were paid for by a grant from the Federal Ministry of Education and Research (BMBF FZK0315668) (http://www.bmbf.de/en/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.