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European Journal of Heart Failure 2008 10(4):396-403; doi:10.1016/j.ejheart.2008.02.008
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© 2008 European Society of Cardiology

Prognostic role of pro- and anti-inflammatory cytokines and their polymorphisms in acute decompensated heart failure

Kati H. Miettinena,*, Johan Lassusb, Veli-Pekka Harjolab, Krista Siirilä-Warisb, John Melinc, Kari R. Punnonend, Markku S. Nieminenb, Markku Laaksoa and Keijo J. Peuhkurinena

a Department of Medicine, Kuopio University Hospital Kuopio, Finland
b Department of Medicine, Helsinki University Hospital Helsinki, Finland
c Department of Medicine, Jyväskylä Central Hospital Jyväskylä, Finland
d Department of Clinical Chemistry, Kuopio University Hospital Kuopio, Finland

* Corresponding author. Department of Medicine, Kuopio University Hospital, P.O. Box 1777, Puijonlaaksontie 2, FI-70210 Kuopio, Finland. Tel.: +358 17 173422; fax: +358 17 173959. E-mail address: kati.h.miettinen{at}kuh.fi (K.H. Miettinen).


  Abstract

Background: Cytokines play an important role in chronic heart failure (HF), but little is known about their involvement in acute decompensated heart failure (ADHF).

Aim: To evaluate the prognostic role of inflammatory cytokines in patients with ADHF.

Methods: Levels of interleukin (IL)-6, tumour necrosis factor alpha (TNF-{alpha}), IL-10 and N-terminal pro-brain natriuretic peptide (NT-proBNP) were measured in 423 patients with ADHF. In addition, appropriate cytokine gene polymorphisms were determined. Survival was followed up to 12 months, and prognostic factors were evaluated.

Results: Elevated levels of IL-6 and TNF-{alpha} were strongly associated with increased 12-month mortality (P < 0.001 for both), whereas the level of IL-10 was predictive only of 6-month mortality (P < 0.01). In multivariate analysis IL-6, chronic renal insufficiency, NT-proBNP, age/10 years' increase and TNF-{alpha} were identified as the most powerful predictors of 12-month mortality. Furthermore, high levels of both IL-6 and NT-proBNP were associated with >7-fold mortality. Cytokine gene polymorphisms were not associated with outcome.

Conclusions: Circulating levels of pro-inflammatory cytokines IL-6 and TNF-{alpha}, and the level of an anti-inflammatory cytokine IL-10, but not their gene polymorphisms, provide novel and important prognostic information in patients with ADHF. Combining measurements of pro-inflammatory cytokines and NT-proBNP seems a promising tool in the prognostic assessment of these patients.

Key Words: Acute heart failure • Cytokines • Prognosis

Received April 5, 2007; Revised November 13, 2007; Accepted February 7, 2008


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