title: Fibroblast growth factor-23 and incident coronary heart disease, heart failure, and cardiovascular mortality: the Atherosclerosis Risk in Communities study.
abstract: BACKGROUND
  Fibroblast growth factor-23 (FGF-23) is a hormone involved in phosphorous regulation and vitamin D metabolism that may be associated with cardiovascular risk, and it is a potential target for intervention. We tested whether elevated FGF-23 is associated with incident coronary heart disease, heart failure, and cardiovascular mortality, even at normal kidney function.
  
  
  RESULTS
  A total of 11 638 Atherosclerosis Risk In Communities study participants, median age 57 at baseline (1990-1992), were followed through 2010. Cox regression was used to evaluate the independent association of baseline serum active FGF-23 with incident outcomes. Models were adjusted for traditional cardiovascular risk factors and estimated glomerular filtration rate. During a median follow-up of 18.6 years, 1125 participants developed coronary heart disease, 1515 developed heart failure, and 802 died of cardiovascular causes. For all 3 outcomes, there was a threshold, whereby FGF-23 was not associated with risk at <40 pg/mL but was positively associated with risk at >40 pg/mL. Compared with those with FGF-23 <40 pg/mL, those in the highest FGF-23 category (≥ 58.8 pg/mL) had a higher risk of incident coronary heart disease (adjusted hazard ratio, 95% CIs: 1.65, 1.40 to 1.94), heart failure (1.75, 1.52 to 2.01), and cardiovascular mortality (1.65, 1.36 to 2.01). Associations were modestly attenuated but remained statistically significant after further adjustment for estimated glomerular filtration rate. In stratified analyses, similar results were observed in African Americans and among persons with normal kidney function.
  
  
  CONCLUSIONS
  High levels of serum FGF-23 were associated with increased risk of coronary heart disease, heart failure, and cardiovascular mortality in this large, biracial, population-based cohort. This association was independent of traditional cardiovascular risk factors and kidney function.
authors.affiliation: Division of Epidemiology & Community Health, University of Minnesota, Minneapolis, MN (P.L.L., A.A., J.S.P.).
authors.forename: Pamela L
authors.initials: PL
authors.lastname: Lutsey
authors.affiliation: Division of Epidemiology & Community Health, University of Minnesota, Minneapolis, MN (P.L.L., A.A., J.S.P.).
authors.forename: Alvaro
authors.initials: A
authors.lastname: Alonso
authors.affiliation: Departments of Epidemiology and Medicine, Johns Hopkins University, Baltimore, MD (E.S., S.K.A., J.C.).
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Selvin
authors.affiliation: Division of Epidemiology & Community Health, University of Minnesota, Minneapolis, MN (P.L.L., A.A., J.S.P.).
authors.forename: James S
authors.initials: JS
authors.lastname: Pankow
authors.affiliation: Division of Cardiology, Johns Hopkins University, Baltimore, MD (E.D.M.).
authors.forename: Erin D
authors.initials: ED
authors.lastname: Michos
authors.affiliation: Departments of Epidemiology and Medicine, Johns Hopkins University, Baltimore, MD (E.S., S.K.A., J.C.).
authors.forename: Sunil K
authors.initials: SK
authors.lastname: Agarwal
authors.affiliation: Department of Epidemiology, University of North Carolina, Chapel Hill, NC (L.R.L.).
authors.forename: Laura R
authors.initials: LR
authors.lastname: Loehr
authors.affiliation: Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN (J.H.E.).
authors.forename: John H
authors.initials: JH
authors.lastname: Eckfeldt
authors.affiliation: Departments of Epidemiology and Medicine, Johns Hopkins University, Baltimore, MD (E.S., S.K.A., J.C.).
authors.forename: Josef
authors.initials: J
authors.lastname: Coresh
mesh_terms: D002318:Cardiovascular Diseases / Q000097:blood* / Q000401:mortality; D003327:Coronary Disease / Q000097:blood* / Q000453:epidemiology / Q000401:mortality; D005260:Female; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000097:blood*; D006333:Heart Failure / Q000097:blood* / Q000453:epidemiology / Q000401:mortality; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012307:Risk Factors; D014481:United States / Q000453:epidemiology
chemical_list: C000717427:FGF23 protein, human; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23
keywords: Atherosclerosis Risk In Communities; cardiovascular mortality; coronary heart disease; epidemiology; fibroblast growth factor 23; heart failure