The Interleukin-1 Axis and Risk of Death in Patients With Acutely Decompensated Heart Failure

Abstract

Background: Soluble ST2 (sST2), which is the soluble form of interleukin (IL)-1 receptor-like 1, identifies risk in acutely decompensated heart failure (ADHF). IL-1β is an inflammatory cytokine that has deleterious effects in myocardial remodeling and function. IL-1β inhibition has beneficial effects after acute myocardial infarction. However, the role of IL-1β in ADHF and its relationship to ST2 remain unclear.

Objectives: This study sought to investigate the relationship between IL-1β and sST2, and the prognostic impact of such a relationship in patients with ADHF.

Methods: This study examined 316 consecutive patients who were hospitalized with ADHF (72 ± 12 years of age, 57% male, and left ventricular ejection fraction 45 ± 17%). Blood samples were collected at presentation, and IL-1β and sST2 levels were measured. All-cause mortality was obtained for all patients at 1 year.

Results: The IL-1β concentration at presentation was associated with prior HF hospitalizations, functional impairment, and higher N-terminal pro-B-type natriuretic peptide and high-sensitivity troponin T concentrations. IL-1β was higher in patients who died during the year after hospitalization (n = 52, 16.5%) (p = 0.005), and the optimal threshold was identified with levels over 49.1 pg/ml (hazard ratio: 2.5; 95% confidence interval: 1.43 to 4.49; p = 0.0014). Circulating IL-1β positively correlated with sST2 (ρ = 0.65; p < 0.001). Considering the prognostic thresholds of IL-1β (≥49.1 pg/ml) and sST2 (≥35.0 ng/ml) concentrations: all patients with low sST2 also presented with low IL-1β; among patients with high sST2, only those with also high IL-1β had a significantly higher risk of death (30% vs. 14%; hazard ratio: 2.52; 95% confidence interval: 1.40 to 4.56; p = 0.002).

Conclusions: Circulating IL-1β concentrations are clinically meaningful in ADHF patients and interplay with the predictive ability of sST2. IL-1 axis-related inflammation signaling may represent a therapeutic target in ADHF.

Keywords: IL-1β; ST2; acute; heart failure; interleukin-1.