title: Fibroblast Growth Factor-23 and Frailty in Elderly Community-Dwelling Individuals: The Cardiovascular Health Study.
abstract: OBJECTIVE
  To evaluate whether fibroblast growth factor 23 (FGF-23) is related to frailty and to characterize the nature of their joint association with mortality.
  
  
  METHODS
  Cross-sectional analysis for frailty and longitudinal cohort analysis for mortality.
  
  
  METHODS
  Cardiovascular Health Study.
  
  
  METHODS
  Community-dwelling individuals (N = 2,977; mean age 77.9 ± 4.7, 40% male, 83% white).
  
  
  METHODS
  The predictor was serum FGF-23 concentration (C-terminal enzyme-linked immunosorbent assay), and the outcomes were frailty status (determined according to frailty phenotype criteria of weight loss, weakness, exhaustion, slowness, and low physical activity) and mortality. Multinomial logistic regression was used to assess the cross-sectional association between FGF-23 and frailty and prefrailty, adjusting for demographic characteristics, cardiovascular disease and risk factors, and kidney markers. Proportional hazards Cox proportional hazards regression was used to assess the association between FGF-23, frailty, and all-cause mortality.
  
  
  RESULTS
  Mean estimated glomerular filtration rate (eGFR) was 64 ± 17 mL/min per 1.73 m(2) . Median FGF-23 was 70.3 RU/mL (interquartile range 53.4-99.2); 52% were prefrail, and 13% were frail. After multivariate adjustment, each doubling in FGF-23 concentration was associated with 38% (95% confidence interval (CI) = 17-62%) higher odds of frailty than of nonfrailty and 16% (95% CI = 3-30%) higher odds of prefrailty. FGF-23 (hazard ratio (HR) = 1.16, 95% CI = 1.10-1.23) and frailty (HR = 1.82, 95% CI = 1.57-2.12) were independently associated with mortality, but neither association was meaningfully attenuated when adjusted for the other.
  
  
  CONCLUSIONS
  In a large cohort of older adults, higher FGF-23 was independently associated with prevalent frailty and prefrailty. FGF-23 and frailty were independent and additive risk factors for mortality. FGF-23 may be a marker for functional outcomes.
authors.affiliation: Division of Nephrology, University of California at San Diego, San Diego, California.|Nephrology Section, Veterans Affairs San Diego Healthcare System, San Diego, California.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Beben
authors.affiliation: Division of Nephrology, University of California at San Diego, San Diego, California.|Nephrology Section, Veterans Affairs San Diego Healthcare System, San Diego, California.
authors.forename: Joachim H
authors.initials: JH
authors.lastname: Ix
authors.affiliation: Department of Medicine, University of California at San Francisco, San Francisco, California.|General Internal Medicine Section, San Francisco Veterans Affairs Medical Center, San Francisco, California.
authors.forename: Michael G
authors.initials: MG
authors.lastname: Shlipak
authors.affiliation: Division of Nephrology, Tufts Medical Center, Boston, Massachusetts.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Sarnak
authors.affiliation: Department of Medicine, University of Pittsburgh and Veteran Affairs Pittsburgh Healthcare System, Pittsburgh, Pennsylvania.|Nephrology Section, Veterans Affairs Pittsburgh Healthcare System, Pittsburgh, Pennsylvania.
authors.forename: Linda F
authors.initials: LF
authors.lastname: Fried
authors.affiliation: Department of Laboratory Medicine, University of Washington, Seattle, Washington.
authors.forename: Andrew N
authors.initials: AN
authors.lastname: Hoofnagle
authors.affiliation: Division of Renal Disease and Hypertension, University of Colorado at Denver, Denver, Colorado.
authors.forename: Michel
authors.initials: M
authors.lastname: Chonchol
authors.affiliation: Division of Nephrology and Kidney Research Institute, Department of Medicine, University of Washington, Seattle, Washington.
authors.forename: Bryan R
authors.initials: BR
authors.lastname: Kestenbaum
authors.affiliation: Division of Nephrology and Kidney Research Institute, Department of Medicine, University of Washington, Seattle, Washington.
authors.forename: Ian H
authors.initials: IH
authors.lastname: de Boer
authors.affiliation: Division of Nephrology, University of California at San Diego, San Diego, California.|Nephrology Section, Veterans Affairs San Diego Healthcare System, San Diego, California.
authors.forename: Dena E
authors.initials: DE
authors.lastname: Rifkin
mesh_terms: D000368:Aged; D000886:Anthropometry; D015415:Biomarkers / Q000097:blood / Q000652:urine; D002318:Cardiovascular Diseases / Q000097:blood* / Q000401:mortality*; D003430:Cross-Sectional Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000097:blood*; D016330:Frail Elderly; D005919:Glomerular Filtration Rate; D006801:Humans; D057187:Independent Living; D008137:Longitudinal Studies; D008297:Male; D010641:Phenotype; D012307:Risk Factors; D011795:Surveys and Questionnaires
chemical_list: D015415:Biomarkers; C000717427:FGF23 protein, human; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23
keywords: fibroblast growth factor 23; frailty; mortality