title: FGF23 modifies the relationship between vitamin D and cardiac remodeling.
abstract: BACKGROUND
  There is growing evidence to support an important role for vitamin D and related hormones, parathyroid hormone and fibroblast growth factor 23 (FGF23), on cardiac remodeling in chronic kidney disease. Our objective was to determine the relationships between vitamin D and cardiac remodeling in chronic kidney disease and the effects of parathyroid hormone and FGF23 on these associations.
  
  
  RESULTS
  In 1431 participants from the Chronic Renal Insufficiency Cohort study, we measured 25-hydroxyvitamin D (25(OH)D), 1,25-dihydroxyvitamin D (1,25(OH)2D), FGF23, and parathyroid hormone and performed quantitative echocardiography. Using linear regression methods, we determined significant negative interactions between 25(OH)D and FGF23 on left ventricular (LV) mass (P=0.016), end-diastolic volume (P=0.029), and end-systolic volumes (P=0.021). In participants with an FGF23 level greater than the median of 123.5 RU/mL, each doubling of 25(OH)D was associated with a 2.5% (95% confidence interval, -4.8, -0.2) lower LV mass. This association was less pronounced with FGF23 levels less than the median (0.4%; 95% confidence interval, -1.9, 2.7). Conversely, in participants with deficient 25(OH)D levels <20 ng/mL, each doubling of FGF23 was associated with a 3.4% (95% confidence interval, 1.2, 5.6) greater LV mass compared with only a 1.6% (95% confidence interval, -0.2, 3.5) difference in participants with sufficient 25(OH)D. Similar findings were observed with 25(OH)D and volumes (P<0.05), and 1,25(OH)2D and LV mass and volumes (P<0.005). There was no effect modification by parathyroid hormone.
  
  
  CONCLUSIONS
  We identified significant interactions among 25(OH)D, 1,25(OH)2D, and FGF23 on cardiac remodeling. Increased LV mass and cavity dilatation were observed with low 25(OH)D and high FGF23. Our findings suggest that consideration of both hormones is crucial to understanding the role of either in cardiac remodeling, and may have important therapeutic implications.
authors.affiliation: Renal Division, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
authors.forename: Bonnie
authors.initials: B
authors.lastname: Ky
authors.forename: Justine
authors.initials: J
authors.lastname: Shults
authors.forename: Martin G
authors.initials: MG
authors.lastname: Keane
authors.forename: Martin St John
authors.initials: MS
authors.lastname: Sutton
authors.forename: Myles
authors.initials: M
authors.lastname: Wolf
authors.forename: Harold I
authors.initials: HI
authors.lastname: Feldman
authors.forename: Peter P
authors.initials: PP
authors.lastname: Reese
authors.forename: Cheryl A
authors.initials: CA
authors.lastname: Anderson
authors.forename: Raymond R
authors.initials: RR
authors.lastname: Townsend
authors.forename: Rajat
authors.initials: R
authors.lastname: Deo
authors.forename: Joan
authors.initials: J
authors.lastname: Lo
authors.forename: Crystal
authors.initials: C
authors.lastname: Gadegbeku
authors.forename: Dean
authors.initials: D
authors.lastname: Carlow
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Sulik
authors.forename: Mary B
authors.initials: MB
authors.lastname: Leonard
mesh_terms: D000368:Aged; D005260:Female; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D051436:Renal Insufficiency, Chronic / Q000503:physiopathology*; D013318:Stroke Volume; D020257:Ventricular Remodeling / Q000502:physiology*; D014807:Vitamin D / Q000031:analogs & derivatives / Q000502:physiology
chemical_list: C000717427:FGF23 protein, human; D014807:Vitamin D; D005346:Fibroblast Growth Factors; C097949:1,25-dihydroxyvitamin D; D000089703:Fibroblast Growth Factor-23; C104450:25-hydroxyvitamin D
keywords: cardiac remodeling; echocardiography; vitamin D