title: Prognostic value of apoptosis markers in advanced heart failure patients.
abstract: OBJECTIVE
  Apoptosis plays an important role in the progression of heart failure (HF). The purpose of this study was to assess whether the pro-apoptotic molecules apoptosis-stimulating fragment (FAS, CD95/APO-1) and tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) predict event-free survival of HF patients.
  
  
  RESULTS
  We assayed soluble (s)FAS and sTRAIL levels in 351 patients with advanced HF. During the median follow-up time of 16 months, 175 patients (50%) experienced the composite endpoints: rehospitalization and death. The hazard increased with sFAS concentrations, with a hazard ratio of 2.3 comparing fourth and first quartiles. This association remained significant after adjustment for B-type natriuretic peptide (BNP) and other risk factors in a Cox regression model (P = 0.014). Patients with high sFAS but low BNP had a comparable event-free survival rate with those with elevated BNP only (P = 0.78). Conversely, high sTRAIL concentrations were related to a better prognosis. Particularly, the risk of mortality dropped by 70% in the fourth quartile of sTRAIL (P = 0.001, multivariable Cox regression model).
  
  
  CONCLUSIONS
  sFAS is an independent risk predictor in advanced HF patients. It may be of particular value for the identification of high-risk patients in addition to BNP. Conversely, sTRAIL appears to be protective and could be an interesting therapeutic agent.
authors.affiliation: Division of Cardiology, Department of Internal Medicine II, Medical University of Vienna, Waehringer Guertel 18-20, Vienna, Austria.
authors.forename: Alexander
authors.initials: A
authors.lastname: Niessner
authors.forename: Philipp J
authors.initials: PJ
authors.lastname: Hohensinner
authors.forename: Kathrin
authors.initials: K
authors.lastname: Rychli
authors.forename: Stephanie
authors.initials: S
authors.lastname: Neuhold
authors.forename: Gerlinde
authors.initials: G
authors.lastname: Zorn
authors.forename: Bernhard
authors.initials: B
authors.lastname: Richter
authors.forename: Martin
authors.initials: M
authors.lastname: Hülsmann
authors.forename: Rudolf
authors.initials: R
authors.lastname: Berger
authors.forename: Deddo
authors.initials: D
authors.lastname: Mörtl
authors.forename: Kurt
authors.initials: K
authors.lastname: Huber
authors.forename: Johann
authors.initials: J
authors.lastname: Wojta
authors.forename: Richard
authors.initials: R
authors.lastname: Pacher
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D017209:Apoptosis / Q000502:physiology; D015415:Biomarkers / Q000097:blood; D017023:Coronary Angiography; D003327:Coronary Disease / Q000097:blood / Q000401:mortality / Q000628:therapy*; D018572:Disease-Free Survival; D005260:Female; D006333:Heart Failure / Q000097:blood* / Q000401:mortality / Q000628:therapy; D006801:Humans; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood*; D011379:Prognosis; D011446:Prospective Studies; D012307:Risk Factors; D012720:Severity of Illness Index; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000097:blood*; D019014:fas Receptor / Q000097:blood*
chemical_list: D015415:Biomarkers; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D019014:fas Receptor; D020097:Natriuretic Peptide, Brain