Prognostic role of pro- and anti-inflammatory cytokines and their polymorphisms in acute decompensated heart failure.
BACKGROUND
Cytokines play an important role in chronic heart failure (HF), but little is known about their involvement in acute decompensated heart failure (ADHF).


OBJECTIVE
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.
Miettinen
Kati H
KH
Department of Medicine, Kuopio University Hospital, Kuopio, Finland. kati.h.miettinen@kuh.fi
Lassus
Johan
J
Harjola
Veli-Pekka
VP
Siirilä-Waris
Krista
K
Melin
John
J
Punnonen
Kari R
KR
Nieminen
Markku S
MS
Laakso
Markku
M
Peuhkurinen
Keijo J
KJ
D000208:Acute Disease; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002303:Cardiac Output, Low / Q000175:diagnosis / Q000235:genetics / Q000276:immunology* / Q000401:mortality; D005260:Female; D006333:Heart Failure / Q000175:diagnosis / Q000235:genetics / Q000276:immunology* / Q000401:mortality; D006801:Humans; D016753:Interleukin-10 / Q000097:blood* / Q000235:genetics*; D015850:Interleukin-6 / Q000097:blood* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood* / Q000235:genetics*; D010446:Peptide Fragments / Q000097:blood* / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D011237:Predictive Value of Tests; D011379:Prognosis; D014409:Tumor Necrosis Factor-alpha / Q000097:blood* / Q000235:genetics*
D015850:Interleukin-6; D010446:Peptide Fragments; D014409:Tumor Necrosis Factor-alpha; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain; D016753:Interleukin-10