Interleukin-6 and Outcomes in Acute Heart Failure: An ASCEND-HF Substudy

ANTONIO L. Perez, JUSTIN L. GRODIN, THANAT CHAIKIJURAJAI, YUPING WU, ADRIAN F. HERNANDEZ, JAVED BUTLER, MARCO METRA, G. MICHAEL FELKER, ADRIAAN A. VOORS, JOHN J. MCMURRAY, PAUL W. ARMSTRONG, CHRISTOPHER O'CONNOR, RANDALL C. STARLING, W. H.WILSON TANG

Research output: Contribution to journalArticlepeer-review

Abstract

Background: The inflammatory cytokine 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. Methods and Results: We analyzed the associations between IL-6 in acute HF, readmission, and mortality (30 and 180 days) using a cohort of 883 hospitalized patients from the ASCEND-HF trial (nesiritide vs placebo). Plasma IL-6 was measured at randomization (baseline), 48–72 hours, and 30 days. The 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 a univariable Cox regression analysis, the baseline IL-6 was associated with 30- and 180-day mortality (hazard ratio per log 1.74, 95% confidence interval 1.09–2.78, P =. 021; hazard ratio 3.23, confidence interval 1.18–8.86, P =. 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 (hazard ratio 8.2, confidence interval 1.2–57.5, P=. 03), but not 180-day mortality in multivariable analysis that included the ASCEND-HF risk model and amino terminal pro-B-type natriuretic peptide as covariates. In comparison with placebo, nesiritide therapy was not associated with differences in serial IL-6 levels. Conclusions: Although elevated IL-6 levels were associated with higher all-cause mortality in acute HF, no independent association with this outcome was identified at baseline or 30-day measurements. In contrast with prior reports, we did not observe any impact of nesiritide over placebo on serial IL-6 levels.

Original languageEnglish (US)
Pages (from-to)670-676
Number of pages7
JournalJournal of Cardiac Failure
Volume27
Issue number6
DOIs
StatePublished - Jun 2021

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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