title: Soluble klotho and mortality: the Ludwigshafen Risk and Cardiovascular Health Study.
abstract: BACKGROUND
  Experimental evidence suggests that soluble klotho (s-klotho), a co-receptor for fibroblast growth factor 23 (FGF23), may modulate cardiovascular risk through multiple mechanisms. However, the predictive value of s-klotho in patients remains unclear. Therefore, the present study examined in a large cohort of patients referred for coronary angiography whether s-klotho is associated with cardiovascular and total mortality.
  
  
  METHODS
  The longitudinal associations between baseline s-klotho and FGF23 concentrations and mortality were evaluated in 2948 participants of the Ludwigshafen Risk and Cardiovascular Health Study (LURIC), referred for coronary angiography.
  
  
  RESULTS
  Mean age of participants was: 63 ± 10 years. Patients with diabetes mellitus (n = 1136) had elevated s-klotho: [440 (430-449) versus 414 (406-421) pg/mL, p < 0.001]. S-klotho decreased in parallel to glomerular filtration rate (GFR) and increased in parallel to FGF23. During a median follow-up of 9.9 years, 874 deaths (30%) occurred, 539 (18%) of which were cardiovascular. After adjustment for cardiovascular risk factors, the hazard ratios in the fourth quartile compared to the first quartile of s-klotho were 1.14 (95%CI, 0.94-1.38; p = 0.187) for all-cause mortality and 1.03 (95%CI, 0.80-1.31; p = 0.845) for cardiovascular mortality. Excess mortality prediction by high levels of baseline FGF23 was not modified by adjustment for baseline s-klotho levels.
  
  
  CONCLUSIONS
  Klotho does not add predictive power to cardiovascular and mortality risk assessment in patients with normal renal function.
authors: Department of Cardiology, University Hospital of the RWTH Aachen, Germany.
authors: Vincent M
authors: VM
authors: Brandenburg
authors: Medical Clinic V, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
authors: Marcus E
authors: ME
authors: Kleber
authors: Department of Nephrology, VU University Medical Center, Amsterdam, The Netherlands.
authors: Marc G
authors: MG
authors: Vervloet
authors: Division of Renal Medicine, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden.
authors: Tobias E
authors: TE
authors: Larsson
authors: Specialist Clinic for Rehabilitation, PV Bad Aussee, Bad Aussee, Austria.
authors: Andreas
authors: A
authors: Tomaschitz
authors: 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: Stefan
authors: S
authors: Pilz
authors: Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Austria.
authors: Tatjana
authors: T
authors: Stojakovic
authors: Medical Clinic V, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
authors: Graciela
authors: G
authors: Delgado
authors: Medical Clinic V, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
authors: Tanja B
authors: TB
authors: Grammer
authors: Department of Cardiology, University Hospital of the RWTH Aachen, Germany.
authors: Nikolaus
authors: N
authors: Marx
authors: 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 Academy, Mannheim, Germany.
authors: Winfried
authors: W
authors: März
authors: Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Austria.
authors: Hubert
authors: H
authors: Scharnagl
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000097:blood* / Q000401:mortality; D017023:Coronary Angiography / Q000379:methods; D003324:Coronary Artery Disease / Q000097:blood; D005260:Female; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000097:blood*; D005500:Follow-Up Studies; D005858:Germany; D005919:Glomerular Filtration Rate; D005966:Glucuronidase / Q000097:blood*; D006801:Humans; D007668:Kidney / Q000502:physiology; D000090265:Klotho Proteins; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012307:Risk Factors
chemical_list: D015415:Biomarkers; C000717427:FGF23 protein, human; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23; D005966:Glucuronidase; D000090265:Klotho Proteins
keywords: Cardiovascular events; Coronary angiography; Coronary artery disease; Fibroblast growth factor 23, FGF23; Outcome