title: Fibroblast growth factor 23 in acute myocardial infarction complicated by cardiogenic shock: a biomarker substudy of the Intraaortic Balloon Pump in Cardiogenic Shock II (IABP-SHOCK II) trial.
abstract: BACKGROUND
  Cardiogenic shock (CS) is the leading cause of death in patients hospitalized with acute myocardial infarction (AMI). Biomarkers might help in risk stratification and understanding of pathophysiology. Preliminary data suggests that patients with CS face a profound increase in the osteocyte-derived hormone fibroblast growth factor 23 (FGF-23), which acts as a negative regulator of serum phosphate levels. The present study aimed to assess the predictive role of FGF-23 for clinical outcome in a large cohort of CS patients with and without renal dysfunction.
  
  
  METHODS
  In the randomized Intraaortic Balloon Pump in Cardiogenic Shock II (IABP-SHOCK II) trial, 600 patients with CS complicating AMI were assigned to therapy with or without IABP. Our predefined biomarker substudy included 182 patients. Blood sampling was performed in a standardized procedure at three different time points (day 1 (day of admission), day 2 and day 3). Differences in outcome of patients with FGF-23 levels<and>median were compared by log-rank testing. Stepwise logistic regression modeling was performed to identify predictors of death at 30 days and Cox regression analysis for time to death during the first year.
  
  
  RESULTS
  At all three time points, nonsurvivors had significantly higher FGF-23 levels compared to survivors (P<0.001 for all). Patients with FGF-23 levels above the median (395 RU/mL [interquartile range 102;2,395]) were characterized by an increased 30-day mortality and 1-year mortality. In multivariable analysis FGF-23 levels remained independent predictors for 30-day (odds ratio per 10log 1.80, 95% confidence interval (CI) 1.11 to 2.92; P=0.02) and 1-year mortality (hazard ratio 1.50, 95% CI 1.11 to 2.04, P=0.009). After stratifying the patients according to their baseline serum creatinine levels, the negative prognostic association of increased FGF-23 was only significant in those with serum creatinine greater than median.
  
  
  CONCLUSIONS
  In CS, high levels of FGF-23 are independently related to a poor clinical outcome. However, this prognostic association appears only to apply in patients with impaired renal function.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT00491036. Registered 22 June 2007.
authors.forename: Georg
authors.initials: G
authors.lastname: Fuernau
authors.forename: Janine
authors.initials: J
authors.lastname: Pöss
authors.forename: Daniel
authors.initials: D
authors.lastname: Denks
authors.forename: Steffen
authors.initials: S
authors.lastname: Desch
authors.forename: Gunnar H
authors.initials: GH
authors.lastname: Heine
authors.forename: Ingo
authors.initials: I
authors.lastname: Eitel
authors.forename: Sarah
authors.initials: S
authors.lastname: Seiler
authors.forename: Suzanne
authors.initials: S
authors.lastname: de Waha
authors.forename: Sebastian
authors.initials: S
authors.lastname: Ewen
authors.forename: Andreas
authors.initials: A
authors.lastname: Link
authors.forename: Gerhard
authors.initials: G
authors.lastname: Schuler
authors.forename: Volker
authors.initials: V
authors.lastname: Adams
authors.forename: Michael
authors.initials: M
authors.lastname: Böhm
authors.forename: Holger
authors.initials: H
authors.lastname: Thiele
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D003404:Creatinine / Q000097:blood; D005260:Female; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000097:blood*; D006801:Humans; D007423:Intra-Aortic Balloon Pumping; D053208:Kaplan-Meier Estimate; D007668:Kidney / Q000503:physiopathology; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood / Q000150:complications* / Q000401:mortality / Q000503:physiopathology / Q000601:surgery; D016016:Proportional Hazards Models; D012770:Shock, Cardiogenic / Q000097:blood / Q000209:etiology* / Q000401:mortality / Q000503:physiopathology; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; C000717427:FGF23 protein, human; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23; D003404:Creatinine