title: Fibroblast growth factor 23 (FGF23) and mortality: the Ludwigshafen Risk and Cardiovascular Health Study.
abstract: BACKGROUND
  Fibroblast growth factor 23 (FGF23) is an important regulatory hormone in phosphate and vitamin D metabolism. Here, we investigated the associations of FGF23 with traditional cardiovascular risk factors and with bone metabolism parameters as well as the impact of FGF23 upon long-term mortality in a large cohort of patients referred for coronary angiography.
  
  
  METHODS
  We examined whether c-term FGF23 concentrations at baseline were associated with cardiovascular and total mortality in 2974 patients from the Ludwigshafen Risk and Cardiovascular Health Study (LURIC). We investigated if these associations were independent from established cardiovascular risk factors as well as from other mineral regulating factors and bone biomarkers such as calcium, parathyroid hormone (PTH), alkaline phosphatase (AP), vitamin D, and serum phosphate.
  
  
  RESULTS
  Mean age of participants was 63 ± 10 years; median c-term FGF23 serum levels were 54 (40-78) RU/ml. During a median follow-up of 9.9 years, 884 deaths (30%) occurred, 545 (18%) of which were cardiovascular. FGF23 significantly and inversely correlated with eGFR. AP, phosphate, and PTH increased in parallel with quartiles of FGF23. Age- and sex-adjusted hazard ratios (HRs) in the fourth quartile compared to the first quartile of FGF23 were 2.54 (95%CI, 2.09-3.09; p < 0.001) for all cause and 2.56 (95% CI, 1.99-3.28; p < 0.001) for cardiovascular mortality. These associations remained significant after additional adjustments for cardiovascular risk factors and bone biomarkers (calcium, PTH, AP, vitamin D, and phosphate): Adjusted HRs were 1.38 (95%CI, 1.26-1.52; p < 0.001) for all-cause and 1.35 (95%CI, 1.20-1.52; p < 0.001) for cardiovascular mortality for each increase by one standard deviation of c-term FGF23.
  
  
  CONCLUSIONS
  In patients undergoing coronary angiography baseline c-term FGF23 levels predict the risk for all-cause and cardiovascular mortality over 9.9 years of follow-up. These associations were independent of established cardiovascular risk factors and serum phosphate.
authors.affiliation: Department of Cardiology, University Hospital of the RWTH Aachen, Germany. Electronic address: VMBrandenburg@aol.com.
authors.forename: Vincent M
authors.initials: VM
authors.lastname: Brandenburg
authors.affiliation: Medical Clinic V, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
authors.forename: Marcus E
authors.initials: ME
authors.lastname: Kleber
authors.affiliation: Department of Nephrology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Marc G
authors.initials: MG
authors.lastname: Vervloet
authors.affiliation: Specialist Clinic for Rehabilitation, PV Bad Aussee, Bad Aussee, Austria.
authors.forename: Andreas
authors.initials: A
authors.lastname: Tomaschitz
authors.affiliation: Department of Cardiology, Medical University of Graz, Graz, Austria; Department of Epidemiology and Biostatistics and EMGO Institute for Health and Care Research, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Stefan
authors.initials: S
authors.lastname: Pilz
authors.affiliation: Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Austria.
authors.forename: Tatjana
authors.initials: T
authors.lastname: Stojakovic
authors.affiliation: Medical Clinic V, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
authors.forename: Graciela
authors.initials: G
authors.lastname: Delgado
authors.affiliation: Medical Clinic V, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
authors.forename: Tanja B
authors.initials: TB
authors.lastname: Grammer
authors.affiliation: Department of Cardiology, University Hospital of the RWTH Aachen, Germany.
authors.forename: Nikolaus
authors.initials: N
authors.lastname: Marx
authors.affiliation: Medical Clinic V, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany; Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Austria; Synlab Center of Laboratory Diagnostics, Heidelberg, Germany.
authors.forename: Winfried
authors.initials: W
authors.lastname: März
authors.affiliation: Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Austria.
authors.forename: Hubert
authors.initials: H
authors.lastname: Scharnagl
mesh_terms: D000368:Aged; D000469:Alkaline Phosphatase / Q000378:metabolism; D001842:Bone and Bones / Q000378:metabolism / Q000473:pathology; D002118:Calcium / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000097:blood* / Q000401:mortality*; D017023:Coronary Angiography; D005260:Female; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000097:blood*; D005500:Follow-Up Studies; D005858:Germany; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D010281:Parathyroid Hormone / Q000378:metabolism; D010710:Phosphates / Q000097:blood; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D014807:Vitamin D / Q000378:metabolism
chemical_list: C000717427:FGF23 protein, human; D010281:Parathyroid Hormone; D010710:Phosphates; D014807:Vitamin D; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23; D000469:Alkaline Phosphatase; D002118:Calcium
keywords: Cardiovascular events; Coronary angiography; Coronary artery disease; Fibroblast growth factor 23, FGF23; Mortality; Outcome- phosphate