title: Fibroblast growth factor 23 and risk of incident stroke in community-living adults.
abstract: OBJECTIVE
  Fibroblast growth factor 23 (FGF23) is a hormone that regulates phosphorus and vitamin D metabolism. Elevated FGF23 concentrations are associated with excess risk of cardiovascular disease. Associations of FGF23 with stroke outcomes are less clear.
  
  
  METHODS
  Using a case-cohort study design, we examined the association of baseline plasma FGF23 concentrations with incident stroke in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study, a cohort of black and white adults aged ≥45 years. FGF23 was measured in 615 participants who developed incident stroke (cases) and in 936 participants randomly selected from the REGARDS cohort (comparison subcohort).
  
  
  RESULTS
  In multivariable-adjusted models, higher calcium and phosphorus concentrations, lower estimated glomerular filtration rate and higher urine albumin excretion were independently associated with higher FGF23. There was no statistically significant association of FGF23 with risk of all-cause stroke in Cox models adjusted for demographic factors and established stroke risk factors (hazard ratio comparing fourth with first quartile 1.19; 95% confidence interval, 0.78-1.82). In prespecified models stratified by stroke subtypes, there was a graded association of FGF23 with risk of cardioembolic stroke in fully adjusted models (quartile 1, reference; quartile 2 hazard ratio, 1.48; 95% confidence interval, 0.63-3.47; quartile 3 hazard ratio, 1.99; 95% confidence interval, 0.89-4.44; quartile 4 hazard ratio, 2.52; 95% confidence interval, 1.08-5.91). There were no statistically significant associations of FGF23 with other ischemic stroke subtypes or with hemorrhagic strokes.
  
  
  CONCLUSIONS
  Higher FGF23 concentrations were associated with higher risk of cardioembolic but not with other stroke subtypes in community-dwelling adults. Additional studies should delineate reasons for these findings.
authors.affiliation: From the Departments of Medicine (B.P., V.G.W., P.M., O.M.G.), Epidemiology (V.J.H., P.M., O.M.G.), and Biostatistics (S.E.J.), University of Alabama at Birmingham; Department of Pathology, University of Vermont, Burlington (N.S.J.); and Department of Neurology, University of Cincinnati, OH (B.M.K.).
authors.forename: Bhupesh
authors.initials: B
authors.lastname: Panwar
authors.affiliation: From the Departments of Medicine (B.P., V.G.W., P.M., O.M.G.), Epidemiology (V.J.H., P.M., O.M.G.), and Biostatistics (S.E.J.), University of Alabama at Birmingham; Department of Pathology, University of Vermont, Burlington (N.S.J.); and Department of Neurology, University of Cincinnati, OH (B.M.K.).
authors.forename: Nancy S
authors.initials: NS
authors.lastname: Jenny
authors.affiliation: From the Departments of Medicine (B.P., V.G.W., P.M., O.M.G.), Epidemiology (V.J.H., P.M., O.M.G.), and Biostatistics (S.E.J.), University of Alabama at Birmingham; Department of Pathology, University of Vermont, Burlington (N.S.J.); and Department of Neurology, University of Cincinnati, OH (B.M.K.).
authors.forename: Virginia J
authors.initials: VJ
authors.lastname: Howard
authors.affiliation: From the Departments of Medicine (B.P., V.G.W., P.M., O.M.G.), Epidemiology (V.J.H., P.M., O.M.G.), and Biostatistics (S.E.J.), University of Alabama at Birmingham; Department of Pathology, University of Vermont, Burlington (N.S.J.); and Department of Neurology, University of Cincinnati, OH (B.M.K.).
authors.forename: Virginia G
authors.initials: VG
authors.lastname: Wadley
authors.affiliation: From the Departments of Medicine (B.P., V.G.W., P.M., O.M.G.), Epidemiology (V.J.H., P.M., O.M.G.), and Biostatistics (S.E.J.), University of Alabama at Birmingham; Department of Pathology, University of Vermont, Burlington (N.S.J.); and Department of Neurology, University of Cincinnati, OH (B.M.K.).
authors.forename: Paul
authors.initials: P
authors.lastname: Muntner
authors.affiliation: From the Departments of Medicine (B.P., V.G.W., P.M., O.M.G.), Epidemiology (V.J.H., P.M., O.M.G.), and Biostatistics (S.E.J.), University of Alabama at Birmingham; Department of Pathology, University of Vermont, Burlington (N.S.J.); and Department of Neurology, University of Cincinnati, OH (B.M.K.).
authors.forename: Brett M
authors.initials: BM
authors.lastname: Kissela
authors.affiliation: From the Departments of Medicine (B.P., V.G.W., P.M., O.M.G.), Epidemiology (V.J.H., P.M., O.M.G.), and Biostatistics (S.E.J.), University of Alabama at Birmingham; Department of Pathology, University of Vermont, Burlington (N.S.J.); and Department of Neurology, University of Cincinnati, OH (B.M.K.).
authors.forename: Suzanne E
authors.initials: SE
authors.lastname: Judd
authors.affiliation: From the Departments of Medicine (B.P., V.G.W., P.M., O.M.G.), Epidemiology (V.J.H., P.M., O.M.G.), and Biostatistics (S.E.J.), University of Alabama at Birmingham; Department of Pathology, University of Vermont, Burlington (N.S.J.); and Department of Neurology, University of Cincinnati, OH (B.M.K.). ogutierr@uab.edu.
authors.forename: Orlando M
authors.initials: OM
authors.lastname: Gutiérrez
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D015331:Cohort Studies; D005260:Female; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000097:blood*; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D011159:Population Surveillance / Q000379:methods; D012307:Risk Factors; D020521:Stroke / Q000097:blood* / Q000175:diagnosis / Q000453:epidemiology*
chemical_list: D015415:Biomarkers; C000717427:FGF23 protein, human; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23
keywords: cardiovascular disease; fibroblast growth factors; stroke