title: Decreased soluble TWEAK levels predict an adverse prognosis in patients with chronic stable heart failure.
abstract: OBJECTIVE
  Tumour necrosis factor (TNF)-like weak inducer of apoptosis (sTWEAK) is a multifunctional cytokine that has recently been implicated in cardiovascular disease. The aim of this study was to define the plasma levels of sTWEAK in patients with stable chronic heart failure and evaluate the possibility of a prognostic impact of sTWEAK.
  
  
  RESULTS
  sTWEAK levels in plasma samples from 364 patients with systolic heart failure were compared with 36 control patients. The median levels of sTWEAK in heart failure patients were significantly lower than those of the control group (217 pg/mL, interquartile range 136-311 vs. 325 pg/mL, interquartile range 250-394 pg/mL). Moreover, sTWEAK levels were lower in patients with ischaemic cardiomyopathy vs. dilated cardiomyopathy and correlated significantly with functional NYHA class. Patients with plasma levels below a ROC-derived cut-off value of 227 pg/mL had a significantly higher mortality rate after 4 years. Upon univariate and multivariate analyses, sTWEAK levels below 227 pg/mL emerged as an independent predictor of subsequent death.
  
  
  CONCLUSIONS
  In contrast to other cytokines shown to be increased in heart failure patients, plasma levels of sTWEAK are significantly reduced in chronic stable heart failure. In addition, lower plasma levels of sTWEAK predict an adverse prognosis independent of established risk markers such as NT-proBNP.
authors.affiliation: Department of Cardiology, Angiology and Pulmology, Heidelberg University Hospital, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany. e.chorianopoulos@med.uni-heidelberg.de
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Chorianopoulos
authors.forename: Mark
authors.initials: M
authors.lastname: Rosenberg
authors.forename: Christian
authors.initials: C
authors.lastname: Zugck
authors.forename: Johanna
authors.initials: J
authors.lastname: Wolf
authors.forename: Hugo A
authors.initials: HA
authors.lastname: Katus
authors.forename: Norbert
authors.initials: N
authors.lastname: Frey
mesh_terms: D015415:Biomarkers / Q000097:blood; D002311:Cardiomyopathy, Dilated / Q000097:blood* / Q000145:classification; D016022:Case-Control Studies; D002908:Chronic Disease; D000074049:Cytokine TWEAK; D005260:Female; D054143:Heart Failure, Systolic / Q000097:blood*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000032:analysis / Q000097:blood; D010446:Peptide Fragments / Q000032:analysis / Q000097:blood; D011379:Prognosis; D012016:Reference Values; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D016019:Survival Analysis; D048069:Tumor Necrosis Factors / Q000097:blood*
chemical_list: D015415:Biomarkers; D000074049:Cytokine TWEAK; D010446:Peptide Fragments; C109743:TNFSF12 protein, human; D048069:Tumor Necrosis Factors; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain