The inflammatory cytokine interleukin-6 (IL-6) has been previously implicated in the pathophysiology of acute decompensated heart failure (HF). Prior observations in acute HF patients have suggested that IL-6 may be associated with outcomes and modulated by nesiritide. We aimed to evaluate the associations between serial IL-6 measurements, mortality and rehospitalization in acute HF.
We analyzed the association between IL-6 in acute HF, readmission and mortality (30 and 180 days) using a cohort of hospitalized 883 patients from the ASCEND-HF trial (nesiritide vs placebo). Plasma IL-6 was measured at randomization (baseline), 48-72 hours, and 30-days. Median IL-6 was highest at baseline (14.1 pg/mL) and decreased at subsequent time points (7.6 pg/mL at 30 days). In univariable Cox-regression analysis, baseline IL-6 was associated with 30- and 180-day mortality (HR per log 1.74, 95% CI 1.09-2.78, p=0.021; HR 3.23, CI 1.18-8.86, p=0.022, respectively). However, there was no association after multivariable adjustment. IL-6 at 48-72 hours was found to be independently associated with 30-day mortality (HR 8.2, CI 1.2-57.5, p = 0.03) but not 180-day mortality in multivariable analysis that included the ASCEND-HF risk model and NT-proBNP as covariates. In comparison to placebo, nesiritide therapy was not associated with differences in serial IL-6 levels.
While elevated IL-6 levels were associated with higher all-cause mortality in acute HF, no independent association with this outcome was identified at baseline and 30-day measurements. Contrary to prior reports, we did not observe any impact of nesiritide over placebo on serial IL-6 levels.