title: High levels of plasma brain natriuretic peptide and interleukin-6 after optimized treatment for heart failure are independent risk factors for morbidity and mortality in patients with congestive heart failure.
abstract: OBJECTIVE
  The aim of this study was to evaluate whether repetitive measurements of plasma levels of neurohumoral factors and cytokines before and after additional treatment are useful for predicting mortality in patients with congestive heart failure (CHF).
  
  
  BACKGROUND
  Neurohumoral and immune activation play an important role in the pathophysiology of CHF. However, the effects of serial changes in these factors on the prognostic value remain unknown.
  
  
  METHODS
  We measured plasma levels of neurohumoral factors and cytokines and left ventricular ejection fraction (LVEF) before and three months after optimized treatment for CHF in 102 consecutive patients with severe CHF (New York Heart Association class III to IV) on admission to our hospital. Physicians who were blind to the plasma neurohumoral factors until study completion treated patients using standard drugs. Patients were monitored for a mean follow-up period of 807 days.
  
  
  RESULTS
  Plasma levels of neurohumoral factors, cytokines and LVEF were significantly improved three months after optimized treatment. Cardiac death occurred in 26 patients. Among 19 variables including LVEF, only a high level of brain natriuretic peptide (BNP) and interleukin-6 (IL-6) at three months after optimized treatment showed significant independent relationships by Cox proportional hazard analysis with a high mortality for patients with CHF.
  
  
  CONCLUSIONS
  These findings indicate that high plasma BNP and IL-6 levels three months after optimized treatment are independent risk factors for mortality in patients with CHF, suggesting that sustained high plasma levels of BNP and IL-6 after additional standard treatment were independent risk factors for mortality in patients with CHF despite improvements in LVEF and symptoms.
authors.affiliation: First Department of Internal Medicine, Shiga University of Medical Science, Otsu, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Maeda
authors.forename: T
authors.initials: T
authors.lastname: Tsutamoto
authors.forename: A
authors.initials: A
authors.lastname: Wada
authors.forename: N
authors.initials: N
authors.lastname: Mabuchi
authors.forename: M
authors.initials: M
authors.lastname: Hayashi
authors.forename: T
authors.initials: T
authors.lastname: Tsutsui
authors.forename: M
authors.initials: M
authors.lastname: Ohnishi
authors.forename: M
authors.initials: M
authors.lastname: Sawaki
authors.forename: M
authors.initials: M
authors.lastname: Fujii
authors.forename: T
authors.initials: T
authors.lastname: Matsumoto
authors.forename: M
authors.initials: M
authors.lastname: Kinoshita
mesh_terms: D000368:Aged; D001685:Biological Factors / Q000097:blood; D002908:Chronic Disease; D016207:Cytokines / Q000097:blood; D005260:Female; D006333:Heart Failure / Q000097:blood* / Q000188:drug therapy / Q000401:mortality* / Q000503:physiopathology; D006801:Humans; D015850:Interleukin-6 / Q000097:blood*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D020097:Natriuretic Peptide, Brain / Q000097:blood*; D009419:Nerve Tissue Proteins / Q000097:blood; D011237:Predictive Value of Tests; D011379:Prognosis; D011446:Prospective Studies; D012307:Risk Factors; D013318:Stroke Volume
chemical_list: D001685:Biological Factors; D016207:Cytokines; D015850:Interleukin-6; D009419:Nerve Tissue Proteins; D020097:Natriuretic Peptide, Brain