Interleukin 6 and Development of Heart Failure With Preserved Ejection Fraction in the General Population

Yook Chin Chia, Lyanne M Kieneker, Gaston van Hassel, S Heleen Binnenmars, Ilja M Nolte, Jelmer J van Zanden, Peter van der Meer, Gerjan Navis, Adriaan A Voors, Stephan J L Bakker, Martin H De Borst, Michele F Eisenga

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Abstract

Background

The cause of heart failure with preserved ejection fraction (HFpEF) is poorly understood, and specific therapies are lacking. Previous studies suggested that inflammation plays a role in the development of HFpEF. Herein, we aimed to investigate in community-dwelling individuals whether a higher plasma interleukin 6 (IL-6) level is associated with an increased risk of developing new-onset heart failure (HF) over time, and specifically HFpEF.

Methods and Results

We performed a case-cohort study based on the PREVEND (Prevention of Renal and Vascular End-Stage Disease) study, a prospective general population-based cohort study. We included 961 participants, comprising 200 participants who developed HF and a random group of 761 controls. HF with reduced ejection fraction or HFpEF was defined on the basis of the left ventricular ejection fraction of 40%, respectively. In Cox proportional hazard regression analyses, IL-6 levels were statistically significantly associated with the development of HF (hazard ratio [HR], 1.28; 95% CI, 1.02-1.61; P=0.03) after adjustment for key risk factors. Specifically, IL-6 levels were significantly associated with the development of HFpEF (HR, 1.59; 95% CI, 1.16-2.19; P=0.004), whereas the association with HF with reduced ejection fraction was nonsignificant (HR, 1.05; 95% CI, 0.75-1.47; P=0.77). In sensitivity analyses, defining HFpEF as left ventricular ejection fraction >= 50%, IL-6 levels were also significantly associated with the development of HFpEF (HR, 1.47; 95% CI, 1.04-2.06; P=0.03) after adjustment for key risk factors.

Conclusions

IL-6 is associated with new-onset HFpEF in community-dwelling individuals, independent of potential confounders. Our findings warrant further research to investigate whether IL-6 might be a novel treatment target to prevent HFpEF.

Original languageEnglish
Article number018549
Pages (from-to)e018549
Number of pages14
JournalJournal of the American Heart Association
Volume10
Issue number11
Early online date2021
DOIs
Publication statusPublished - 1-Jun-2021

Keywords

  • general population
  • heart failure
  • heart failure with preserved ejection fraction
  • interleukin 6
  • LEFT-VENTRICULAR HYPERTROPHY
  • PROINFLAMMATORY CYTOKINES
  • NATRIURETIC PEPTIDE
  • OLDER-ADULTS
  • DYSFUNCTION
  • MORBIDITY
  • MORTALITY
  • ONSET
  • RISK
  • MICROALBUMINURIA

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