title: Fibroblast growth factor-23 and cardiovascular disease in the general population: the Multi-Ethnic Study of Atherosclerosis.
abstract: BACKGROUND
  Fibroblast growth factor-23 (FGF-23) is a phosphate regulatory hormone that directly stimulates left ventricular hypertrophy in experimental models. The role of FGF-23 in cardiovascular disease development in the general population is unclear. We tested associations of FGF-23 with major subclinical and clinical cardiovascular disease outcomes in a large prospective cohort.
  
  
  RESULTS
  We evaluated 6547 participants from the Multi-Ethnic Study of Atherosclerosis (MESA) who were initially free of cardiovascular disease. We measured serum FGF-23 using the Kainos immunoassay. The MESA measured left ventricular mass by MRI, coronary calcium by computed tomography, and carotid intima-media thickness by ultrasound. The MESA adjudicated incident heart failure, coronary heart disease, and stroke by medical record review. After adjustment, the highest FGF-23 quartile was associated with an estimated 2.4-g greater left ventricular mass (95% confidence interval, 0.4-4.5 greater) and a 26% greater odds of higher coronary calcium scores (95% confidence interval, 9%-46% greater) compared with the lowest quartile. During 7.5-year follow-up, each 20-pg/mL higher FGF-23 concentration was associated with a 19% greater risk of heart failure (95% confidence interval, 3%-37% greater) and a 14% greater risk of coronary heart disease (95% confidence interval, 1%-28% greater). FGF-23 was not associated with carotid intima-media thickness or stroke.
  
  
  CONCLUSIONS
  Higher serum FGF-23 concentrations are associated with subclinical cardiac disease and with new heart failure and coronary disease events, but not with carotid intima-media thickness or stroke. FGF-23 may be a novel cardiovascular risk factor in the general population.
authors.affiliation: From the Kidney Research Institute, Department of Medicine, Division of Nephrology (B.K., M.C.S., C.R.-C., J.R., D.R., I.H.d.B.), Department of Laboratory Medicine (A.N.H.), Cardiovascular Health Research Unit, Departments of Medicine and Epidemiology (D.S.S.), and Department of Epidemiology (M.B.), University of Washington, Seattle; Division of Nephrology, Department of Medicine, University of California at San Diego (J.H.I.); Nephrology Section, Veterans Affairs San Diego Healthcare System, CA (J.H.I.); and Division of Preventive Medicine, Department of Family and Preventive Medicine, University of California at San Diego (J.H.I.); Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD (J.A.C.L.); and Department of Radiology, Tufts-New England Medical Center, Boston, MA (J.F.P.). brk@u.wasington.edu.
authors.forename: Bryan
authors.initials: B
authors.lastname: Kestenbaum
authors.affiliation: From the Kidney Research Institute, Department of Medicine, Division of Nephrology (B.K., M.C.S., C.R.-C., J.R., D.R., I.H.d.B.), Department of Laboratory Medicine (A.N.H.), Cardiovascular Health Research Unit, Departments of Medicine and Epidemiology (D.S.S.), and Department of Epidemiology (M.B.), University of Washington, Seattle; Division of Nephrology, Department of Medicine, University of California at San Diego (J.H.I.); Nephrology Section, Veterans Affairs San Diego Healthcare System, CA (J.H.I.); and Division of Preventive Medicine, Department of Family and Preventive Medicine, University of California at San Diego (J.H.I.); Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD (J.A.C.L.); and Department of Radiology, Tufts-New England Medical Center, Boston, MA (J.F.P.).
authors.forename: Michael C
authors.initials: MC
authors.lastname: Sachs
authors.affiliation: From the Kidney Research Institute, Department of Medicine, Division of Nephrology (B.K., M.C.S., C.R.-C., J.R., D.R., I.H.d.B.), Department of Laboratory Medicine (A.N.H.), Cardiovascular Health Research Unit, Departments of Medicine and Epidemiology (D.S.S.), and Department of Epidemiology (M.B.), University of Washington, Seattle; Division of Nephrology, Department of Medicine, University of California at San Diego (J.H.I.); Nephrology Section, Veterans Affairs San Diego Healthcare System, CA (J.H.I.); and Division of Preventive Medicine, Department of Family and Preventive Medicine, University of California at San Diego (J.H.I.); Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD (J.A.C.L.); and Department of Radiology, Tufts-New England Medical Center, Boston, MA (J.F.P.).
authors.forename: Andy N
authors.initials: AN
authors.lastname: Hoofnagle
authors.affiliation: From the Kidney Research Institute, Department of Medicine, Division of Nephrology (B.K., M.C.S., C.R.-C., J.R., D.R., I.H.d.B.), Department of Laboratory Medicine (A.N.H.), Cardiovascular Health Research Unit, Departments of Medicine and Epidemiology (D.S.S.), and Department of Epidemiology (M.B.), University of Washington, Seattle; Division of Nephrology, Department of Medicine, University of California at San Diego (J.H.I.); Nephrology Section, Veterans Affairs San Diego Healthcare System, CA (J.H.I.); and Division of Preventive Medicine, Department of Family and Preventive Medicine, University of California at San Diego (J.H.I.); Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD (J.A.C.L.); and Department of Radiology, Tufts-New England Medical Center, Boston, MA (J.F.P.).
authors.forename: David S
authors.initials: DS
authors.lastname: Siscovick
authors.affiliation: From the Kidney Research Institute, Department of Medicine, Division of Nephrology (B.K., M.C.S., C.R.-C., J.R., D.R., I.H.d.B.), Department of Laboratory Medicine (A.N.H.), Cardiovascular Health Research Unit, Departments of Medicine and Epidemiology (D.S.S.), and Department of Epidemiology (M.B.), University of Washington, Seattle; Division of Nephrology, Department of Medicine, University of California at San Diego (J.H.I.); Nephrology Section, Veterans Affairs San Diego Healthcare System, CA (J.H.I.); and Division of Preventive Medicine, Department of Family and Preventive Medicine, University of California at San Diego (J.H.I.); Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD (J.A.C.L.); and Department of Radiology, Tufts-New England Medical Center, Boston, MA (J.F.P.).
authors.forename: Joachim H
authors.initials: JH
authors.lastname: Ix
authors.affiliation: From the Kidney Research Institute, Department of Medicine, Division of Nephrology (B.K., M.C.S., C.R.-C., J.R., D.R., I.H.d.B.), Department of Laboratory Medicine (A.N.H.), Cardiovascular Health Research Unit, Departments of Medicine and Epidemiology (D.S.S.), and Department of Epidemiology (M.B.), University of Washington, Seattle; Division of Nephrology, Department of Medicine, University of California at San Diego (J.H.I.); Nephrology Section, Veterans Affairs San Diego Healthcare System, CA (J.H.I.); and Division of Preventive Medicine, Department of Family and Preventive Medicine, University of California at San Diego (J.H.I.); Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD (J.A.C.L.); and Department of Radiology, Tufts-New England Medical Center, Boston, MA (J.F.P.).
authors.forename: Cassianne
authors.initials: C
authors.lastname: Robinson-Cohen
authors.affiliation: From the Kidney Research Institute, Department of Medicine, Division of Nephrology (B.K., M.C.S., C.R.-C., J.R., D.R., I.H.d.B.), Department of Laboratory Medicine (A.N.H.), Cardiovascular Health Research Unit, Departments of Medicine and Epidemiology (D.S.S.), and Department of Epidemiology (M.B.), University of Washington, Seattle; Division of Nephrology, Department of Medicine, University of California at San Diego (J.H.I.); Nephrology Section, Veterans Affairs San Diego Healthcare System, CA (J.H.I.); and Division of Preventive Medicine, Department of Family and Preventive Medicine, University of California at San Diego (J.H.I.); Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD (J.A.C.L.); and Department of Radiology, Tufts-New England Medical Center, Boston, MA (J.F.P.).
authors.forename: Joao A C
authors.initials: JA
authors.lastname: Lima
authors.affiliation: From the Kidney Research Institute, Department of Medicine, Division of Nephrology (B.K., M.C.S., C.R.-C., J.R., D.R., I.H.d.B.), Department of Laboratory Medicine (A.N.H.), Cardiovascular Health Research Unit, Departments of Medicine and Epidemiology (D.S.S.), and Department of Epidemiology (M.B.), University of Washington, Seattle; Division of Nephrology, Department of Medicine, University of California at San Diego (J.H.I.); Nephrology Section, Veterans Affairs San Diego Healthcare System, CA (J.H.I.); and Division of Preventive Medicine, Department of Family and Preventive Medicine, University of California at San Diego (J.H.I.); Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD (J.A.C.L.); and Department of Radiology, Tufts-New England Medical Center, Boston, MA (J.F.P.).
authors.forename: Joseph F
authors.initials: JF
authors.lastname: Polak
authors.affiliation: From the Kidney Research Institute, Department of Medicine, Division of Nephrology (B.K., M.C.S., C.R.-C., J.R., D.R., I.H.d.B.), Department of Laboratory Medicine (A.N.H.), Cardiovascular Health Research Unit, Departments of Medicine and Epidemiology (D.S.S.), and Department of Epidemiology (M.B.), University of Washington, Seattle; Division of Nephrology, Department of Medicine, University of California at San Diego (J.H.I.); Nephrology Section, Veterans Affairs San Diego Healthcare System, CA (J.H.I.); and Division of Preventive Medicine, Department of Family and Preventive Medicine, University of California at San Diego (J.H.I.); Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD (J.A.C.L.); and Department of Radiology, Tufts-New England Medical Center, Boston, MA (J.F.P.).
authors.forename: Marc
authors.initials: M
authors.lastname: Blondon
authors.affiliation: From the Kidney Research Institute, Department of Medicine, Division of Nephrology (B.K., M.C.S., C.R.-C., J.R., D.R., I.H.d.B.), Department of Laboratory Medicine (A.N.H.), Cardiovascular Health Research Unit, Departments of Medicine and Epidemiology (D.S.S.), and Department of Epidemiology (M.B.), University of Washington, Seattle; Division of Nephrology, Department of Medicine, University of California at San Diego (J.H.I.); Nephrology Section, Veterans Affairs San Diego Healthcare System, CA (J.H.I.); and Division of Preventive Medicine, Department of Family and Preventive Medicine, University of California at San Diego (J.H.I.); Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD (J.A.C.L.); and Department of Radiology, Tufts-New England Medical Center, Boston, MA (J.F.P.).
authors.forename: John
authors.initials: J
authors.lastname: Ruzinski
authors.affiliation: From the Kidney Research Institute, Department of Medicine, Division of Nephrology (B.K., M.C.S., C.R.-C., J.R., D.R., I.H.d.B.), Department of Laboratory Medicine (A.N.H.), Cardiovascular Health Research Unit, Departments of Medicine and Epidemiology (D.S.S.), and Department of Epidemiology (M.B.), University of Washington, Seattle; Division of Nephrology, Department of Medicine, University of California at San Diego (J.H.I.); Nephrology Section, Veterans Affairs San Diego Healthcare System, CA (J.H.I.); and Division of Preventive Medicine, Department of Family and Preventive Medicine, University of California at San Diego (J.H.I.); Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD (J.A.C.L.); and Department of Radiology, Tufts-New England Medical Center, Boston, MA (J.F.P.).
authors.forename: Denise
authors.initials: D
authors.lastname: Rock
authors.affiliation: From the Kidney Research Institute, Department of Medicine, Division of Nephrology (B.K., M.C.S., C.R.-C., J.R., D.R., I.H.d.B.), Department of Laboratory Medicine (A.N.H.), Cardiovascular Health Research Unit, Departments of Medicine and Epidemiology (D.S.S.), and Department of Epidemiology (M.B.), University of Washington, Seattle; Division of Nephrology, Department of Medicine, University of California at San Diego (J.H.I.); Nephrology Section, Veterans Affairs San Diego Healthcare System, CA (J.H.I.); and Division of Preventive Medicine, Department of Family and Preventive Medicine, University of California at San Diego (J.H.I.); Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD (J.A.C.L.); and Department of Radiology, Tufts-New England Medical Center, Boston, MA (J.F.P.).
authors.forename: Ian H
authors.initials: IH
authors.lastname: de Boer
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D050197:Atherosclerosis / Q000097:blood / Q000453:epidemiology* / Q000208:ethnology*; D015415:Biomarkers / Q000097:blood; D002118:Calcium / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000097:blood / Q000453:epidemiology* / Q000208:ethnology*; D059168:Carotid Intima-Media Thickness; D015331:Cohort Studies; D003331:Coronary Vessels / Q000378:metabolism; D005260:Female; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000097:blood*; D006352:Heart Ventricles / Q000473:pathology; D006801:Humans; D015994:Incidence; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012307:Risk Factors; D014481:United States
chemical_list: D015415:Biomarkers; C000717427:FGF23 protein, human; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23; D002118:Calcium
keywords: cardiovascular diseases; carotid intima-media thickness; coronary disease; fibroblast growth factor 23; heart failure; hypertrophy, left ventricular; stroke