title: Prognostic utility of growth differentiation factor-15 in patients with chronic heart failure.
abstract: OBJECTIVE
  We explored the prognostic utility of growth differentiation factor (GDF)-15 in patients with chronic heart failure (CHF).
  
  
  BACKGROUND
  Growth differentiation factor-15 is a stress-responsive member of the transforming growth factor-beta cytokine superfamily. It has recently been observed that patients with CHF have increased circulating levels of GDF-15. The relations of GDF-15 to other biomarkers and to mortality in CHF have never been studied.
  
  
  METHODS
  Circulating levels of GDF-15 were determined by immunoradiometric assay in 455 patients with CHF with a median left ventricular ejection fraction (LVEF) of 32% (interquartile range 25% to 39%).
  
  
  RESULTS
  The median GDF-15 level was 1,949 ng/l (interquartile range 1,194 to 3,577); 74.9% of the patients presented with GDF-15 levels >1,200 ng/l, the upper limit of normal in healthy elderly individuals. The GDF-15 levels were closely related to New York Heart Association (NYHA) functional class and to amino-terminal pro-B-type natriuretic peptide (NT-proBNP). The risk of death during follow-up increased with increasing quartiles of GDF-15. Mortality rates at 48 months were 10.0%, 9.4%, 33.4%, and 56.2% in the respective quartiles (p < 0.001). After adjustment for clinical variables and established biomarkers of adverse prognosis, including NT-proBNP, renal dysfunction, anemia, and hyperuricemia, GDF-15 remained an independent predictor of mortality (adjusted hazard ratio for 1 U in the Ln scale 2.26; 95% confidence interval 1.52 to 3.37; p < 0.001). Growth differentiation factor 15 provided prognostic information in clinically relevant patient subgroups (defined according to age, body mass index, heart failure etiology, concomitant medical therapy, renal function, and the levels of hemoglobin and uric acid) and added prognostic information to NYHA functional class, LVEF, and NT-proBNP.
  
  
  CONCLUSIONS
  Growth differentiation factor 15 is a new biomarker of the risk of death in patients with CHF that provides prognostic information beyond established clinical and biochemical markers.
authors.affiliation: Department of Cardiology and Angiology, Hannover Medical School, Hannover, Germany.
authors.forename: Tibor
authors.initials: T
authors.lastname: Kempf
authors.forename: Stephan
authors.initials: S
authors.lastname: von Haehling
authors.forename: Timo
authors.initials: T
authors.lastname: Peter
authors.forename: Tim
authors.initials: T
authors.lastname: Allhoff
authors.forename: Mariantonietta
authors.initials: M
authors.lastname: Cicoira
authors.forename: Wolfram
authors.initials: W
authors.lastname: Doehner
authors.forename: Piotr
authors.initials: P
authors.lastname: Ponikowski
authors.forename: Gerasimos S
authors.initials: GS
authors.lastname: Filippatos
authors.forename: Piotr
authors.initials: P
authors.lastname: Rozentryt
authors.forename: Helmut
authors.initials: H
authors.lastname: Drexler
authors.forename: Stefan D
authors.initials: SD
authors.lastname: Anker
authors.forename: Kai C
authors.initials: KC
authors.lastname: Wollert
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D019485:Bone Morphogenetic Proteins / Q000097:blood*; D015331:Cohort Studies; D005260:Female; D055436:Growth Differentiation Factor 15; D006333:Heart Failure / Q000097:blood* / Q000175:diagnosis / Q000401:mortality*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D012307:Risk Factors; D015996:Survival Rate