title: Fibroblast growth factor-23 and incident atrial fibrillation: the Multi-Ethnic Study of Atherosclerosis (MESA) and the Cardiovascular Health Study (CHS).
abstract: BACKGROUND
  Fibroblast growth factor-23 (FGF-23) is a hormone that promotes urinary phosphate excretion and regulates vitamin D metabolism. Circulating FGF-23 concentrations increase markedly in chronic kidney disease and are associated with increased risk of clinical cardiovascular events. FGF-23 may promote atrial fibrillation (AF) by inducing left ventricular hypertrophy and diastolic and left atrial dysfunction.
  
  
  RESULTS
  We tested the associations of circulating FGF-23 concentration with incident AF among 6398 participants in the Multi-Ethnic Study of Atherosclerosis (MESA) and 1350 participants in the Cardiovascular Health Study (CHS), all free of clinical cardiovascular disease at baseline. Over a median of 7.7 and 8.0 years of follow-up, we observed 291 and 229 incident AF events in MESA and CHS, respectively. In multivariable Cox proportional hazards models, each 2-fold-higher FGF-23 concentration was associated with a 41% higher risk of incident AF in MESA (hazard ratio, 1.41; 95% confidence interval, 1.13-1.76; P=0.003) and a 30% higher risk of incident AF in CHS (hazard ratio, 1.30; 95% confidence interval, 1.05-1.61; P=0.016) after adjustment for potential confounding characteristics, including kidney disease. Serum phosphate concentration was significantly associated with incident AF in MESA (hazard ratio, 1.15 per 0.5 mg/dL; 95% confidence interval, 1.02-1.31; P=0.023) but not CHS. In MESA, an association of low estimated glomerular filtration rate with incident AF was partially attenuated by adjustment for FGF-23.
  
  
  CONCLUSIONS
  Higher circulating FGF-23 concentration is associated with incident AF and may, in part, explain the link between chronic kidney disease and AF.
authors.affiliation: From the Division of Cardiology (J.S.M., K.K.P.), Division of Nephrology and Kidney Research Institute (J.S.M., M.C.S., R.K., B.K., I.H.d.B.), Cardiovascular Health Research Unit, Departments of Medicine and Epidemiology (S.R.H., D.S.S.), Department of Epidemiology (S.R.H., B.K., I.H.d.B.), and Department of Laboratory Medicine (A.N.H.), University of Washington, Seattle; Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis (A.A.); Division of Renal Diseases and Hypertension, University of Colorado, Denver (M.C.); Division of Cardiology, Electrophysiology Section, University of Pennsylvania, Philadelphia (R.D.); and Division of Nephrology and Hypertension, Department of Medicine, University of California San Diego, and San Diego VA Healthcare System, San Diego (J.H.I.). jmathew@cardiology.washington.edu.
authors.forename: Jehu S
authors.initials: JS
authors.lastname: Mathew
authors.affiliation: From the Division of Cardiology (J.S.M., K.K.P.), Division of Nephrology and Kidney Research Institute (J.S.M., M.C.S., R.K., B.K., I.H.d.B.), Cardiovascular Health Research Unit, Departments of Medicine and Epidemiology (S.R.H., D.S.S.), Department of Epidemiology (S.R.H., B.K., I.H.d.B.), and Department of Laboratory Medicine (A.N.H.), University of Washington, Seattle; Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis (A.A.); Division of Renal Diseases and Hypertension, University of Colorado, Denver (M.C.); Division of Cardiology, Electrophysiology Section, University of Pennsylvania, Philadelphia (R.D.); and Division of Nephrology and Hypertension, Department of Medicine, University of California San Diego, and San Diego VA Healthcare System, San Diego (J.H.I.).
authors.forename: Michael C
authors.initials: MC
authors.lastname: Sachs
authors.affiliation: From the Division of Cardiology (J.S.M., K.K.P.), Division of Nephrology and Kidney Research Institute (J.S.M., M.C.S., R.K., B.K., I.H.d.B.), Cardiovascular Health Research Unit, Departments of Medicine and Epidemiology (S.R.H., D.S.S.), Department of Epidemiology (S.R.H., B.K., I.H.d.B.), and Department of Laboratory Medicine (A.N.H.), University of Washington, Seattle; Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis (A.A.); Division of Renal Diseases and Hypertension, University of Colorado, Denver (M.C.); Division of Cardiology, Electrophysiology Section, University of Pennsylvania, Philadelphia (R.D.); and Division of Nephrology and Hypertension, Department of Medicine, University of California San Diego, and San Diego VA Healthcare System, San Diego (J.H.I.).
authors.forename: Ronit
authors.initials: R
authors.lastname: Katz
authors.affiliation: From the Division of Cardiology (J.S.M., K.K.P.), Division of Nephrology and Kidney Research Institute (J.S.M., M.C.S., R.K., B.K., I.H.d.B.), Cardiovascular Health Research Unit, Departments of Medicine and Epidemiology (S.R.H., D.S.S.), Department of Epidemiology (S.R.H., B.K., I.H.d.B.), and Department of Laboratory Medicine (A.N.H.), University of Washington, Seattle; Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis (A.A.); Division of Renal Diseases and Hypertension, University of Colorado, Denver (M.C.); Division of Cardiology, Electrophysiology Section, University of Pennsylvania, Philadelphia (R.D.); and Division of Nephrology and Hypertension, Department of Medicine, University of California San Diego, and San Diego VA Healthcare System, San Diego (J.H.I.).
authors.forename: Kristen K
authors.initials: KK
authors.lastname: Patton
authors.affiliation: From the Division of Cardiology (J.S.M., K.K.P.), Division of Nephrology and Kidney Research Institute (J.S.M., M.C.S., R.K., B.K., I.H.d.B.), Cardiovascular Health Research Unit, Departments of Medicine and Epidemiology (S.R.H., D.S.S.), Department of Epidemiology (S.R.H., B.K., I.H.d.B.), and Department of Laboratory Medicine (A.N.H.), University of Washington, Seattle; Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis (A.A.); Division of Renal Diseases and Hypertension, University of Colorado, Denver (M.C.); Division of Cardiology, Electrophysiology Section, University of Pennsylvania, Philadelphia (R.D.); and Division of Nephrology and Hypertension, Department of Medicine, University of California San Diego, and San Diego VA Healthcare System, San Diego (J.H.I.).
authors.forename: Susan R
authors.initials: SR
authors.lastname: Heckbert
authors.affiliation: From the Division of Cardiology (J.S.M., K.K.P.), Division of Nephrology and Kidney Research Institute (J.S.M., M.C.S., R.K., B.K., I.H.d.B.), Cardiovascular Health Research Unit, Departments of Medicine and Epidemiology (S.R.H., D.S.S.), Department of Epidemiology (S.R.H., B.K., I.H.d.B.), and Department of Laboratory Medicine (A.N.H.), University of Washington, Seattle; Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis (A.A.); Division of Renal Diseases and Hypertension, University of Colorado, Denver (M.C.); Division of Cardiology, Electrophysiology Section, University of Pennsylvania, Philadelphia (R.D.); and Division of Nephrology and Hypertension, Department of Medicine, University of California San Diego, and San Diego VA Healthcare System, San Diego (J.H.I.).
authors.forename: Andrew N
authors.initials: AN
authors.lastname: Hoofnagle
authors.affiliation: From the Division of Cardiology (J.S.M., K.K.P.), Division of Nephrology and Kidney Research Institute (J.S.M., M.C.S., R.K., B.K., I.H.d.B.), Cardiovascular Health Research Unit, Departments of Medicine and Epidemiology (S.R.H., D.S.S.), Department of Epidemiology (S.R.H., B.K., I.H.d.B.), and Department of Laboratory Medicine (A.N.H.), University of Washington, Seattle; Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis (A.A.); Division of Renal Diseases and Hypertension, University of Colorado, Denver (M.C.); Division of Cardiology, Electrophysiology Section, University of Pennsylvania, Philadelphia (R.D.); and Division of Nephrology and Hypertension, Department of Medicine, University of California San Diego, and San Diego VA Healthcare System, San Diego (J.H.I.).
authors.forename: Alvaro
authors.initials: A
authors.lastname: Alonso
authors.affiliation: From the Division of Cardiology (J.S.M., K.K.P.), Division of Nephrology and Kidney Research Institute (J.S.M., M.C.S., R.K., B.K., I.H.d.B.), Cardiovascular Health Research Unit, Departments of Medicine and Epidemiology (S.R.H., D.S.S.), Department of Epidemiology (S.R.H., B.K., I.H.d.B.), and Department of Laboratory Medicine (A.N.H.), University of Washington, Seattle; Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis (A.A.); Division of Renal Diseases and Hypertension, University of Colorado, Denver (M.C.); Division of Cardiology, Electrophysiology Section, University of Pennsylvania, Philadelphia (R.D.); and Division of Nephrology and Hypertension, Department of Medicine, University of California San Diego, and San Diego VA Healthcare System, San Diego (J.H.I.).
authors.forename: Michel
authors.initials: M
authors.lastname: Chonchol
authors.affiliation: From the Division of Cardiology (J.S.M., K.K.P.), Division of Nephrology and Kidney Research Institute (J.S.M., M.C.S., R.K., B.K., I.H.d.B.), Cardiovascular Health Research Unit, Departments of Medicine and Epidemiology (S.R.H., D.S.S.), Department of Epidemiology (S.R.H., B.K., I.H.d.B.), and Department of Laboratory Medicine (A.N.H.), University of Washington, Seattle; Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis (A.A.); Division of Renal Diseases and Hypertension, University of Colorado, Denver (M.C.); Division of Cardiology, Electrophysiology Section, University of Pennsylvania, Philadelphia (R.D.); and Division of Nephrology and Hypertension, Department of Medicine, University of California San Diego, and San Diego VA Healthcare System, San Diego (J.H.I.).
authors.forename: Rajat
authors.initials: R
authors.lastname: Deo
authors.affiliation: From the Division of Cardiology (J.S.M., K.K.P.), Division of Nephrology and Kidney Research Institute (J.S.M., M.C.S., R.K., B.K., I.H.d.B.), Cardiovascular Health Research Unit, Departments of Medicine and Epidemiology (S.R.H., D.S.S.), Department of Epidemiology (S.R.H., B.K., I.H.d.B.), and Department of Laboratory Medicine (A.N.H.), University of Washington, Seattle; Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis (A.A.); Division of Renal Diseases and Hypertension, University of Colorado, Denver (M.C.); Division of Cardiology, Electrophysiology Section, University of Pennsylvania, Philadelphia (R.D.); and Division of Nephrology and Hypertension, Department of Medicine, University of California San Diego, and San Diego VA Healthcare System, San Diego (J.H.I.).
authors.forename: Joachim H
authors.initials: JH
authors.lastname: Ix
authors.affiliation: From the Division of Cardiology (J.S.M., K.K.P.), Division of Nephrology and Kidney Research Institute (J.S.M., M.C.S., R.K., B.K., I.H.d.B.), Cardiovascular Health Research Unit, Departments of Medicine and Epidemiology (S.R.H., D.S.S.), Department of Epidemiology (S.R.H., B.K., I.H.d.B.), and Department of Laboratory Medicine (A.N.H.), University of Washington, Seattle; Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis (A.A.); Division of Renal Diseases and Hypertension, University of Colorado, Denver (M.C.); Division of Cardiology, Electrophysiology Section, University of Pennsylvania, Philadelphia (R.D.); and Division of Nephrology and Hypertension, Department of Medicine, University of California San Diego, and San Diego VA Healthcare System, San Diego (J.H.I.).
authors.forename: David S
authors.initials: DS
authors.lastname: Siscovick
authors.affiliation: From the Division of Cardiology (J.S.M., K.K.P.), Division of Nephrology and Kidney Research Institute (J.S.M., M.C.S., R.K., B.K., I.H.d.B.), Cardiovascular Health Research Unit, Departments of Medicine and Epidemiology (S.R.H., D.S.S.), Department of Epidemiology (S.R.H., B.K., I.H.d.B.), and Department of Laboratory Medicine (A.N.H.), University of Washington, Seattle; Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis (A.A.); Division of Renal Diseases and Hypertension, University of Colorado, Denver (M.C.); Division of Cardiology, Electrophysiology Section, University of Pennsylvania, Philadelphia (R.D.); and Division of Nephrology and Hypertension, Department of Medicine, University of California San Diego, and San Diego VA Healthcare System, San Diego (J.H.I.).
authors.forename: Bryan
authors.initials: B
authors.lastname: Kestenbaum
authors.affiliation: From the Division of Cardiology (J.S.M., K.K.P.), Division of Nephrology and Kidney Research Institute (J.S.M., M.C.S., R.K., B.K., I.H.d.B.), Cardiovascular Health Research Unit, Departments of Medicine and Epidemiology (S.R.H., D.S.S.), Department of Epidemiology (S.R.H., B.K., I.H.d.B.), and Department of Laboratory Medicine (A.N.H.), University of Washington, Seattle; Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis (A.A.); Division of Renal Diseases and Hypertension, University of Colorado, Denver (M.C.); Division of Cardiology, Electrophysiology Section, University of Pennsylvania, Philadelphia (R.D.); and Division of Nephrology and Hypertension, Department of Medicine, University of California San Diego, and San Diego VA Healthcare System, San Diego (J.H.I.).
authors.forename: Ian H
authors.initials: IH
authors.lastname: de Boer
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001281:Atrial Fibrillation / Q000097:blood* / Q000453:epidemiology / Q000209:etiology; D015897:Comorbidity; D005006:Ethnicity / Q000706:statistics & numerical data; D005260:Female; D051518:Fibroblast Growth Factor 3 / Q000097:blood* / Q000502:physiology; D000089703:Fibroblast Growth Factor-23; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate; D006333:Heart Failure / Q000453:epidemiology; D006801:Humans; D017379:Hypertrophy, Left Ventricular / Q000097:blood; D008297:Male; D008875:Middle Aged; D010710:Phosphates / Q000378:metabolism* / Q000493:pharmacokinetics; D016016:Proportional Hazards Models; D051436:Renal Insufficiency, Chronic / Q000097:blood* / Q000150:complications / Q000453:epidemiology; D012307:Risk Factors; D014481:United States / Q000453:epidemiology; D018487:Ventricular Dysfunction, Left / Q000097:blood / Q000209:etiology / Q000503:physiopathology; D020257:Ventricular Remodeling; D014807:Vitamin D / Q000031:analogs & derivatives / Q000096:biosynthesis
chemical_list: C000717427:FGF23 protein, human; C496444:FGF3 protein, human; D051518:Fibroblast Growth Factor 3; D010710:Phosphates; D014807:Vitamin D; C097949:1,25-dihydroxyvitamin D; D000089703:Fibroblast Growth Factor-23
keywords: atrial fibrillation; fibroblast growth factors; minerals; renal insufficiency, chronic