The clinical significance of interleukin-6 in heart failure: results from the BIOSTAT-CHF study

George Markousis-Mavrogenis, Jasper Tromp, Wouter Ouwerkerk, Matt Devalaraja, Stefan D. Anker, John G. Cleland, Kenneth Dickstein, Gerasimos S. Filippatos, Pim van der Harst, Chim C. Lang, Marco Metra, Leong L. Ng, Piotr Ponikowski, Nilesh J. Samani, Faiez Zannad, Aeilko H. Zwinderman, Hans L. Hillege, Dirk J. van Veldhuisen, Rahul Kakkar, Adriaan A. VoorsPeter van der Meer*

*Corresponding author for this work

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Aims Inflammation is a central process in the pathophysiology of heart failure (HF), but trials targeting tumour necrosis factor (TNF)-alpha were largely unsuccessful. Interleukin (IL)-6 is an important inflammatory mediator and might constitute a potential pharmacologic target in HF. However, little is known regarding the association between IL-6 and clinical characteristics, outcomes and other inflammatory biomarkers in HF. We thus aimed to identify and characterize these associations. Methods and results Interleukin-6 was measured in 2329 patients [89.4% with a left ventricular ejection fraction (LVEF) 40% independently predicted elevated IL-6 levels. IL-6 independently predicted the primary outcome [HR (95% confidence interval) per doubling: 1.16 (1.11-1.21), P <0.001], all-cause mortality [1.22 (1.16-1.29), P <0.001] and CV as well as non-CV mortality [1.16 (1.09-1.24), P <0.001; 1.31 (1.18-1.45), P <0.001], but did not improve discrimination in previously published risk models. Conclusions In a large, heterogeneous cohort of HF patients, elevated IL-6 levels were found in more than 50% of patients and were associated with iron deficiency, reduced LVEF, atrial fibrillation and poorer clinical outcomes. These findings warrant further investigation of IL-6 as a potential therapeutic target in specific HF subpopulations.

Original languageEnglish
Pages (from-to)965-973
Number of pages9
JournalEuropean Journal of Heart Failure
Issue number8
Publication statusPublished - Aug-2019


  • Interleukin-6
  • Heart failure
  • Inflammation
  • Anaemia
  • Adverse events
  • Procalcitonin
  • IL-6

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