title: Fibroblast growth factor 23, the ankle-brachial index, and incident peripheral artery disease in the Cardiovascular Health Study.
abstract: BACKGROUND
  Fibroblast growth factor 23 (FGF23) has emerged as a novel risk factor for mortality and cardiovascular events. Its association with the ankle-brachial index (ABI) and clinical peripheral artery disease (PAD) is less known.
  
  
  METHODS
  Using data (N = 3143) from the Cardiovascular Health Study (CHS), a cohort of community dwelling adults >65 years of age, we analyzed the cross-sectional association of FGF23 with ABI and its association with incident clinical PAD events during 9.8 years of follow up using multinomial logistic regression and Cox proportional hazards models respectively.
  
  
  RESULTS
  The prevalence of cardiovascular disease (CVD) and traditional risk factors like diabetes, coronary artery disease, and heart failure increased across higher quartiles of FGF23. Compared to those with ABI of 1.1-1.4, FGF23 per doubling at baseline was associated with prevalent PAD (ABI < 0.9) although this association was attenuated after adjusting for CVD risk factors, and kidney function (OR 0.91, 95% CI 0.76-1.08). FGF23 was not associated with high ABI (>1.4) (OR 1.06, 95% CI 0.75-1.51). Higher FGF23 was associated with incidence of PAD events in unadjusted, demographic adjusted, and CVD risk factor adjusted models (HR 2.26, 95% CI 1.28-3.98; highest versus lowest quartile). The addition of estimated glomerular filtration and urine albumin to creatinine ratio to the model however, attenuated these findings (HR 1.46, 95% CI, 0.79-2.70).
  
  
  CONCLUSIONS
  In community dwelling older adults, FGF23 was not associated with baseline low or high ABI or incident PAD events after adjusting for confounding variables. These results suggest that FGF23 may primarily be associated with adverse cardiovascular outcomes through non atherosclerotic mechanisms.
authors: Tufts Medical Center, Boston, USA.
authors: Pranav S
authors: PS
authors: Garimella
authors: University of California, San Diego, USA.
authors: Joachim H
authors: JH
authors: Ix
authors: University of Washington, Seattle, USA.
authors: Ronit
authors: R
authors: Katz
authors: University of Colorado, Denver, USA.
authors: Michel B
authors: MB
authors: Chonchol
authors: University of Washington, Seattle, USA.
authors: Bryan R
authors: BR
authors: Kestenbaum
authors: University of Washington, Seattle, USA.
authors: Ian H
authors: IH
authors: de Boer
authors: University of Washington, Seattle, USA.
authors: David S
authors: DS
authors: Siscovick
authors: University of Texas Southwestern Medical Center, Dallas, USA.
authors: Shani
authors: S
authors: Shastri
authors: University of California, San Francisco, USA.
authors: Jade S
authors: JS
authors: Hiramoto
authors: University of California, San Francisco, USA.
authors: Michael G
authors: MG
authors: Shlipak
authors: Tufts Medical Center, Boston, USA. Electronic address: msarnak@tuftsmedicalcenter.org.
authors: Mark J
authors: MJ
authors: Sarnak
mesh_terms: D000368:Aged; D055109:Ankle Brachial Index; D002318:Cardiovascular Diseases / Q000503:physiopathology; D003430:Cross-Sectional Studies; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000097:blood*; D006801:Humans; D015994:Incidence; D058729:Peripheral Arterial Disease / Q000097:blood / Q000453:epidemiology*; D012307:Risk Factors
chemical_list: C000717427:FGF23 protein, human; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23
keywords: Ankle-brachial index; Cardiovascular disease; Chronic kidney disease; Fibroblast growth factor; Peripheral artery disease