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J Am Coll Cardiol, 2000; 36:1587-1593
© 2000 by the American College of Cardiology Foundation
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CLINICAL STUDY

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

Keiko Maeda, MD, >a, Takayoshi Tsutamoto, MD, >a, Atsuyuki Wada, MD, >a, Naoko Mabuchi, MD, >a, Masaru Hayashi, MD, >a, Takashi Tsutsui, MD, >a, Masato Ohnishi, MD, >a, Masahide Sawaki, MD, >a, Masanori Fujii, MD, >a, Takehiro Matsumoto, MD, >a and Masahiko Kinoshita, MD, >a

a First Department of Internal Medicine, Shiga University of Medical Science, Otsu, Japan

Manuscript received December 29, 1999; revised manuscript received April 19, 2000, accepted June 19, 2000.

Reprint requests and correspondence: Dr. Takayoshi Tsutamoto, First Department of Internal Medicine, Shiga University of Medical Science, Tsukinowa, Seta, Otsu 520-2192, Japan
tsutamoto{at}belle.shiga-med.ac.jp

OBJECTIVES

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.

Abbreviations and Acronyms
  ACE = angiotensin-converting enzyme
  ANP = atrial natriuretic peptide
  BNP = brain natriuretic peptide
  CHF = congestive heart failure
  ET-1 = endothelin-1
  IL-6 = interleukin-6
  LVEF = left ventricular ejection fraction
  MI = myocardial infarction
  NE = norepinephrine
  NYHA = New York Heart Association
  TNF-alpha = tumor necrosis factor-alpha




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