title: The fibroblast growth factor-23 and Vitamin D emerge as nontraditional risk factors and may affect cardiovascular risk.
abstract: OBJECTIVE
  Fibroblast growth factor-23 (FGF-23) and vitamin D are hormones involved in phosphate homoeostasis. They also directly influence cardiomyocyte hypertrophy. We examined whether the relationships between levels of vitamin D or FGF-23, cardiac phenotype and outcome were independent of established cardiac biomarkers in a large cohort of community-dwelling elderly subjects.
  
  
  METHODS
  Plasma levels of FGF-23 and vitamin D were measured in 1851 men and women (65-84 years) resident in the Lazio region of Italy. Participants were referred to eight cardiology centres for clinical examination, electrocardiography, comprehensive Doppler echocardiography and blood sampling. All-cause mortality or hospitalizations were available after a median follow-up of 47 months with record linkage of administrative data.
  
  
  RESULTS
  Vitamin D deficiency (<20 ng mL(-1) ) was found in 72.3% of subjects, but FGF-23 levels were normal [74 (58-97) RU per mL]. After adjustment for cardiovascular risk factors and morbidities, low concentrations of vitamin D and high levels of FGF-23 were associated with a higher left ventricular (LV) mass index. Levels of FGF-23 [hazard ratio (HR) (95% confidence interval (CI)) 1.71 (1.28-2.28), P < 0.0001] but not vitamin D [0.76 (0.57-1.01), P = 0.08] were independently associated with mortality after adjustment for clinical risk factors and two cardiac markers together (N-terminal pro-brain natriuretic peptide and high-sensitivity cardiac troponin T), but did not predict hospital admission. People with above median values of FGF-23 and below median values of vitamin D had greater LV hypertrophy and higher mortality.
  
  
  CONCLUSIONS
  In community-dwelling elderly individuals with highly prevalent vitamin D deficiency, FGF-23 levels were associated with LV hypertrophy and predicted mortality independently of two robust cardiac biomarkers. A causal relationship was not demonstrated, but the hormones involved in mineral metabolism emerged as nontraditional risk factors and may affect cardiovascular risk.
authors.affiliation: Department of Cardiovascular Research, IRCCS-Istituto di Ricerche Farmacologiche "Mario Negri", Milan, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Masson
authors.affiliation: Lazio Regional Health Service, Rome, Italy.
authors.forename: N
authors.initials: N
authors.lastname: Agabiti
authors.affiliation: Laboratory of Endocrinology, Ospedale Luigi Sacco, Milan, Italy.
authors.forename: T
authors.initials: T
authors.lastname: Vago
authors.affiliation: ASL Roma D, Rome, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Miceli
authors.affiliation: Lazio Regional Health Service, Rome, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Mayer
authors.affiliation: Laboratory of Endocrinology, Ospedale Luigi Sacco, Milan, Italy.
authors.forename: T
authors.initials: T
authors.lastname: Letizia
authors.affiliation: Roche Diagnostics, Penzberg, Germany.
authors.forename: U
authors.initials: U
authors.lastname: Wienhues-Thelen
authors.affiliation: Department of Cardiovascular Diseases, S. Giovanni-Addolorata Hospital, Rome, Italy.
authors.forename: G F
authors.initials: GF
authors.lastname: Mureddu
authors.affiliation: Lazio Regional Health Service, Rome, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Davoli
authors.affiliation: Department of Cardiovascular Diseases, S. Giovanni-Addolorata Hospital, Rome, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Boccanelli
authors.affiliation: Department of Cardiovascular Research, IRCCS-Istituto di Ricerche Farmacologiche "Mario Negri", Milan, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Latini
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000378:metabolism; D003430:Cross-Sectional Studies; D005260:Female; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000378:metabolism*; D006801:Humans; D017379:Hypertrophy, Left Ventricular / Q000097:blood / Q000209:etiology*; D008297:Male; D010641:Phenotype; D011379:Prognosis; D012307:Risk Factors; D014807:Vitamin D / Q000378:metabolism*; D014808:Vitamin D Deficiency / Q000150:complications
chemical_list: D015415:Biomarkers; C000717427:FGF23 protein, human; D014807:Vitamin D; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23
keywords: community; elderly; fibroblast growth factor-23; left ventricular mass; prognosis; vitamin D