title: The pro-apoptotic serum activity is an independent mortality predictor of patients with heart failure.
abstract: OBJECTIVE
  Systemic inflammation with elevated serum levels of circulating pro-inflammatory cytokines is a major determinant of prognosis in heart failure (HF). Since serum of patients with HF induces apoptosis of endothelial cells (EC), we aimed to determine whether the pro-apoptotic activity in the serum may predict prognosis of patients with HF.
  
  
  RESULTS
  We measured the pro-apoptotic activity in the serum of 48 patients with HF of different aetiology by an ex vivo cell culture assay and subsequently monitored these patients for the single endpoint all-cause mortality. During follow-up, 16 patients died and 11 patients received a heart transplant. Survivors had a lower pro-apoptotic serum activity (P=0.007). By univariate analysis, pro-apoptotic serum activity, NYHA class, pro-BNP, low blood pressure, and creatinine levels were significantly associated with mortality. In a multivariable stepwise Cox-regression model, the pro-apoptotic serum activity (adjusted hazard ratio, HR=1.85 per %, P=0.008), elevated pro-BNP levels (HR=9.35 per log[pro-BNP], P=0.001), and low blood pressure (HR=0.96 per mmHg, P=0.041) remained as independent predictors of death.
  
  
  CONCLUSIONS
  In this exploratory study, the pro-apoptotic serum capacity is independently associated with a worse prognosis in patients with HF, suggesting that the assessment of serum-induced EC apoptosis could provide an integrative estimate of the deleterious effects of various pro-inflammatory cytokines and other cytotoxic factors in HF.
authors.affiliation: Division of Molecular Cardiology, Department of Internal Medicine IV, University of Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt, Germany.
authors.forename: Lothar
authors.initials: L
authors.lastname: Rössig
authors.forename: Stephan
authors.initials: S
authors.lastname: Fichtlscherer
authors.forename: Christopher
authors.initials: C
authors.lastname: Heeschen
authors.forename: Jürgen
authors.initials: J
authors.lastname: Berger
authors.forename: Stefanie
authors.initials: S
authors.lastname: Dimmeler
authors.forename: Andreas M
authors.initials: AM
authors.lastname: Zeiher
mesh_terms: D017209:Apoptosis; D015415:Biomarkers / Q000097:blood; D002303:Cardiac Output, Low / Q000097:blood / Q000209:etiology / Q000401:mortality*; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood*; D009419:Nerve Tissue Proteins / Q000097:blood*; D010446:Peptide Fragments / Q000097:blood*; D011379:Prognosis; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000097:blood*; D012044:Regression Analysis; D016019:Survival Analysis; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D009419:Nerve Tissue Proteins; D010446:Peptide Fragments; D047888:Receptors, Tumor Necrosis Factor, Type I; D014409:Tumor Necrosis Factor-alpha; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain