Abstract 2794: Prognostic Role of Pro- and Anti-inflammatory Cytokines and Their Polymorphisms in Acute Decompensated Heart Failure
BACKGROUND : Although the role of cytokines in the pathogenesis and prognosis of chronic heart failure (HF) is well established, relatively little is known regarding their involvement in acute decompensated heart failure (ADHF). Therefore, we set out to study the prognostic role of circulating inflammatory cytokines as well as their appropriate gene polymorphisms in the setting of ADHF.
METHODS : Patients included in the Finnish Acute Heart Failure (FINN-AKVA) study (n = 620) were characterized according to the new acute HF guidelines as having congestive HF (65 %), pulmonary oedema (26 %), isolated right HF (5 %), cardiogenic shock (2 %) or hypertensive crisis (2 %). In the present study, patients with either pulmonary oedema or congestive HF were included (ntot = 423). Levels of interleukin (IL) 6, tumor necrosis factor alpha (TNF-α), IL-10 and N-terminal pro-brain natriuretic peptide (NT-proBNP) were measured ≤ 48 hours from hospital admission. In addition, appropriate cytokine gene polymorphisms (IL6 –174G>C, TNF-308G>A, IL10 –1082G>A, IL10 –592C>A) were screened. Survival was followed up to 12 months.
RESULTS : Elevated IL-6 and TNF-α levels were strongly associated with 12-month mortality (P < 0.001 for both; tertile analysis). The level of IL-10 was predictive of 6-month mortality (P < 0.05). In multivariate analysis, IL-6 level > 14.2 pg/mL was identified as the most powerful predictor of 12-month mortality (HR 1.90, P < 0.01), followed by chronic renal insufficiency (HR 1.90, P < 0.05), NT-proBNP level > 4080 pg/mL (HR 1.73, P < 0.05), age / 10 years incr. (HR 1.59, P < 0.001), and TNF-α level > 1.51 pg/mL (HR 1.54, P < 0.05). Moreover, patients belonging to the highest tertiles of both NT-proBNP and IL-6 / TNF-α had > 5-fold mortality rate at 12 months than patients belonging to the lowest tertiles of these biomarkers. The cytokine gene polymorphisms were not associated with outcome.
CONCLUSIONS : Circulating levels of proinflammatory cytokines IL-6 and TNF-α, 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. Furthermore, combining data of proinflammatory cytokines and NT-proBNP seems a promising tool in the prognostic assessment of these patients.