title: Circulating fibroblast growth factor-23 is associated with vascular dysfunction in the community.
abstract: OBJECTIVE
  Subjects with chronic kidney disease (CKD) are at higher risk for cardiovascular (CV) disease than the general population. These patients have elevated circulating levels of FGF23, which predict for increased mortality in CKD patients on hemodialysis. Since CV disease is a major cause of death in CKD, we investigated the association between FGF23 and vascular function.
  
  
  RESULTS
  We employed a community-based cohort of subjects aged 70, the PIVUS study (n=967), to investigate the relation between serum FGF23, endothelium function and arterial stiffness. Higher FGF23 was weakly associated with both impaired endothelium-dependent (beta=-0.08, p<0.05) and endothelium-independent (beta=-0.08, p<0.01) vasodilation. The association was stronger in subjects with eGFR> or =90mL/min/1.73m(2) (beta=-0.19 and beta=-0.22, respectively, p<0.001). In addition, higher FGF23 was associated with increased arterial stiffness exclusively in subjects with an age-adjusted impaired renal function (eGFR<60mL/min/1.73m(2)) (beta=0.26, p<0.001). All associations were independent of gender, biochemical covariates and established CV risk factors.
  
  
  CONCLUSIONS
  Higher serum FGF23 levels, even within the normal range, are independently associated with impaired vasoreactivity and increased arterial stiffness in the community. Additional studies are required to determine possible direct vascular effects of FGF23 and whether FGF23 is a modifiable CV risk factor.
authors.affiliation: Department of Medical Sciences, Uppsala University Hospital, Sweden.
authors.forename: Majd A I
authors.initials: MA
authors.lastname: Mirza
authors.forename: Anders
authors.initials: A
authors.lastname: Larsson
authors.forename: Lars
authors.initials: L
authors.lastname: Lind
authors.forename: Tobias E
authors.initials: TE
authors.lastname: Larsson
mesh_terms: D000368:Aged; D015331:Cohort Studies; D004730:Endothelium, Vascular / Q000473:pathology; D005260:Female; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000097:blood* / Q000502:physiology; D005919:Glomerular Filtration Rate; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood*; D008297:Male; D015233:Models, Statistical; D011897:Random Allocation; D012016:Reference Values; D012307:Risk Factors; D012737:Sex Factors; D011795:Surveys and Questionnaires; D014664:Vasodilation
chemical_list: C000717427:FGF23 protein, human; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23