title: A multi-biomarker risk score improves prediction of long-term mortality in patients with advanced heart failure.
abstract: BACKGROUND
  Accurate risk prediction is important for an adequate management of heart failure (HF) patients. We assessed the incremental prognostic ability of a multi-biomarker approach in advanced HF.
  
  
  METHODS
  In 349 patients with advanced HF (median 75 years, 66% male) we investigated the incremental prognostic value of 12 novel biomarkers involved in different pathophysiological pathways including inflammation, immunological activation, oxidative stress, cell growth, remodeling, angiogenesis and apoptosis.
  
  
  RESULTS
  During a median follow-up of 4.9 years 55.9% of patients died. Using multivariable Cox regression and bootstrap variable-selection age, chronic obstructive pulmonary disease, N-terminal pro-B-type natriuretic peptide (NT-proBNP) and the following 5 novel biomarkers were retained in the best mortality prediction model: the chemokine fractalkine, the angiogenic and mitogenic hepatocyte growth factor (HGF), the growth differentiation factor 15 (GDF-15) influencing cardiac remodeling and apoptosis, and the 2 pro-apoptotic molecules soluble apoptosis-stimulating fragment (sFAS) and soluble tumor necrosis factor-related apoptosis-inducing ligand (sTRAIL). This multi-biomarker score had strong discriminatory power for 5-year mortality (area under the Receiver Operating Characteristic curve [AUC]=0.81) and improved risk prediction beyond the prognostic power of a comprehensive conventional risk score including known clinical predictors and NT-proBNP (AUC=0.77). Net reclassification confirmed a significant improvement of individual risk prediction (p=0.003).
  
  
  CONCLUSIONS
  Risk prediction by a multi-biomarker score is superior to a conventional risk score including clinical parameters and NT-proBNP. Additional predictive information from different biological pathways reflects the multisystemic character of HF.
authors.affiliation: Department of Cardiology, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Richter
authors.forename: Lorenz
authors.initials: L
authors.lastname: Koller
authors.forename: Philipp J
authors.initials: PJ
authors.lastname: Hohensinner
authors.forename: Gerlinde
authors.initials: G
authors.lastname: Zorn
authors.forename: Mira
authors.initials: M
authors.lastname: Brekalo
authors.forename: Rudolf
authors.initials: R
authors.lastname: Berger
authors.forename: Deddo
authors.initials: D
authors.lastname: Mörtl
authors.forename: Gerald
authors.initials: G
authors.lastname: Maurer
authors.forename: Richard
authors.initials: R
authors.lastname: Pacher
authors.forename: Kurt
authors.initials: K
authors.lastname: Huber
authors.forename: Johann
authors.initials: J
authors.lastname: Wojta
authors.forename: Martin
authors.initials: M
authors.lastname: Hülsmann
authors.forename: Alexander
authors.initials: A
authors.lastname: Niessner
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D054428:Chemokine CX3CL1 / Q000097:blood; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D055436:Growth Differentiation Factor 15 / Q000097:blood; D006333:Heart Failure / Q000097:blood* / Q000175:diagnosis / Q000401:mortality*; D017228:Hepatocyte Growth Factor / Q000097:blood; D006801:Humans; D008297:Male; D008875:Middle Aged; D009026:Mortality / Q000639:trends; D020097:Natriuretic Peptide, Brain / Q000097:blood*; D010446:Peptide Fragments / Q000097:blood*; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012307:Risk Factors; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000097:blood; D013997:Time Factors
chemical_list: D015415:Biomarkers; C515538:CX3CL1 protein, human; D054428:Chemokine CX3CL1; C526140:GDF15 protein, human; D055436:Growth Differentiation Factor 15; D010446:Peptide Fragments; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain; D017228:Hepatocyte Growth Factor