title: Association of Fibroblast Growth Factor-23 Levels and Angiotensin-Converting Enzyme Inhibition in Chronic Systolic Heart Failure.
abstract: OBJECTIVE
  The aim of this study was to evaluate the association of fibroblast growth factor (FGF)-23 with clinical and laboratory findings, the prognostic value of FGF-23, and the relationship between angiotensin-converting enzyme inhibitor (ACEi) therapy, FGF-23 levels, and outcomes in patients with chronic systolic heart failure (HF).
  
  
  BACKGROUND
  FGF-23 is a bone-derived hormone regulating mineral metabolism. Higher FGF-23 levels are associated with an increased risk of cardiovascular mortality or HF development. Mechanisms leading to increased FGF-23 and its prognostic value have not been thoroughly studied in HF.
  
  
  METHODS
  FGF-23 was measured in 369 patients (mean age 59 ± 11 years, 84% male) with systolic HF. Patients were followed for adverse events (e.g., death, urgent heart transplantation, ventricular assist device implantation).
  
  
  RESULTS
  Tricuspid regurgitation severity, chronic kidney disease (CKD), alkaline phosphatase concentrations, inferior vena cava dilation, and absence of ACEi therapy were independently associated with FGF-23. FGF-23 was independently associated with outcomes in patients without CKD (hazard ratio [HR]: 1.43, 95% confidence interval [CI]: 1.14 to 1.78), but not in CKD patients (HR: 1.12, 95% CI: 0.87 to 1.45). In patients without CKD and with FGF-23 in the highest tertile, ACEi therapy was associated with a lower risk of adverse events (HR: 0.42, 95% CI: 0.21 to 0.81), whereas no association was seen in the remaining patients (HR: 1.18, 95% CI: 0.52 to 2.70).
  
  
  CONCLUSIONS
  In systolic HF, elevated FGF-23 is an independent predictor of adverse events, particularly in patients with preserved renal function. The association of FGF-23 with adverse events likely reflects early alterations of renal hemodynamics and renin-angiotensin system activation. Increased FGF-23 may identify a subset of HF patients benefiting from ACEi therapy.
authors.affiliation: Department of Cardiology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic; Center for Cardiovascular Prevention of the First Faculty of Medicine, Charles University and Thomayer Hospital, Prague, Czech Republic.
authors.forename: Peter
authors.initials: P
authors.lastname: Wohlfahrt
authors.affiliation: Department of Cardiology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.
authors.forename: Vojtech
authors.initials: V
authors.lastname: Melenovsky
authors.affiliation: Department of Cardiology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.
authors.forename: Martin
authors.initials: M
authors.lastname: Kotrc
authors.affiliation: Department of Cardiology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.
authors.forename: Jan
authors.initials: J
authors.lastname: Benes
authors.affiliation: Department of Laboratory Methods, Institute for Clinical and Experimental Medicine-IKEM, Prague, Czech Republic; 3rd Medical Faculty, Charles University, Prague, Czech Republic.
authors.forename: Antonin
authors.initials: A
authors.lastname: Jabor
authors.affiliation: Department of Laboratory Methods, Institute for Clinical and Experimental Medicine-IKEM, Prague, Czech Republic; 3rd Medical Faculty, Charles University, Prague, Czech Republic.
authors.forename: Janka
authors.initials: J
authors.lastname: Franekova
authors.affiliation: Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Sophia
authors.initials: S
authors.lastname: Lemaire
authors.affiliation: Department of Cardiology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.
authors.forename: Josef
authors.initials: J
authors.lastname: Kautzner
authors.affiliation: Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts. Electronic address: pjarolim@partners.org.
authors.forename: Petr
authors.initials: P
authors.lastname: Jarolim
mesh_terms: D015502:Absorptiometry, Photon / Q000379:methods; D000368:Aged; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D015415:Biomarkers; D002908:Chronic Disease; D015331:Cohort Studies; D015150:Echocardiography, Doppler; D005260:Female; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000097:blood*; D054143:Heart Failure, Systolic / Q000097:blood* / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D006801:Humans; D053208:Kaplan-Meier Estimate; D007676:Kidney Failure, Chronic / Q000209:etiology* / Q000401:mortality / Q000503:physiopathology; D007677:Kidney Function Tests; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011237:Predictive Value of Tests; D011379:Prognosis; D012189:Retrospective Studies; D018570:Risk Assessment; D012720:Severity of Illness Index; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D015415:Biomarkers; C000717427:FGF23 protein, human; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23
keywords: adverse events; angiotensin-converting enzyme inhibitor; fibroblast growth factor-23; heart failure; outcome