title: Fibroblast growth factor-23 and cardiac structure and function.
abstract: BACKGROUND
  Fibroblast growth factor-23 (FGF-23) is a phosphaturic factor previously associated with left ventricular hypertrophy and systolic dysfunction among individuals with chronic kidney disease. Whether FGF-23 acts directly to induce left ventricular hypertrophy, potentially independent of its klotho coreceptor, remains uncertain. We investigated associations of FGF-23 with cardiac structural abnormalities among individuals with a broad range of kidney function and explored potential biological mechanisms using cardiac magnetic resonance imaging and histology in klotho-null mice, an established model of constitutively elevated FGF-23.
  
  
  RESULTS
  Among 887 participants with coronary artery disease in the Heart and Soul Study, FGF-23 was modestly associated with worse left ventricular ejection fraction (-1.0% per standard deviation increase in lnFGF-23; standard error, 0.4%), but was not associated with the overall prevalence of concentric hypertrophy (odds ratio, 1.5; CI, 0.9 to 2.4) or eccentric hypertrophy (odds ratio, 1.1; CI, 0.9 to 1.3). FGF-23 was only associated with concentric hypertrophy among individuals with diminished kidney function (eGFR <60 mL/min per 1.73 m(2); odds ratio, 2.3; CI, 1.0 to 5.3; P-interaction=0.28). Comparing klotho-null with wild-type mice, null mice did not have greater left ventricular mass (P=0.37) or a lower ejection fraction (P=0.94).
  
  
  CONCLUSIONS
  Together, our results suggest that FGF-23 is unlikely to have major effects on cardiovascular structure and function among patients free of substantial chronic kidney disease, and these effects may not be independent of the klotho coreceptor.
authors: Department of Epidemiology, Harvard School of Public Health, Boston, MA.
authors: Isha
authors: I
authors: Agarwal
authors: Noriko
authors: N
authors: Ide
authors: Joachim H
authors: JH
authors: Ix
authors: Bryan
authors: B
authors: Kestenbaum
authors: Beate
authors: B
authors: Lanske
authors: Nelson B
authors: NB
authors: Schiller
authors: Mary A
authors: MA
authors: Whooley
authors: Kenneth J
authors: KJ
authors: Mukamal
mesh_terms: D000368:Aged; D000818:Animals; D015415:Biomarkers / Q000097:blood; D003324:Coronary Artery Disease / Q000097:blood* / Q000453:epidemiology / Q000473:pathology / Q000503:physiopathology; D005260:Female; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000097:blood*; D005966:Glucuronidase / Q000172:deficiency / Q000235:genetics; D006801:Humans; D017379:Hypertrophy, Left Ventricular / Q000097:blood / Q000453:epidemiology / Q000473:pathology / Q000503:physiopathology; D007668:Kidney / Q000503:physiopathology; D000090265:Klotho Proteins; D016014:Linear Models; D016015:Logistic Models; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008875:Middle Aged; D015999:Multivariate Analysis; D016017:Odds Ratio; D015995:Prevalence; D051436:Renal Insufficiency, Chronic / Q000097:blood / Q000453:epidemiology / Q000503:physiopathology; D012307:Risk Factors; D013318:Stroke Volume; D013599:Systole; D014481:United States / Q000453:epidemiology; D015854:Up-Regulation; D018487:Ventricular Dysfunction, Left / Q000097:blood / Q000453:epidemiology / Q000473:pathology / Q000503:physiopathology; D016277:Ventricular Function, Left
chemical_list: D015415:Biomarkers; C000717427:FGF23 protein, human; C000717428:Fgf23 protein, mouse; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23; D005966:Glucuronidase; D000090265:Klotho Proteins
keywords: chronic kidney disease; hypertrophy; structure