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Circulating interleukins in relation to coronary artery disease, atrial fibrillation and ischemic stroke and its

Shuai Yuan1, Ang Lin2, Qi-Qiang He3

  • 1Unit of Cardiovascular and Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.

International Journal of Cardiology
|April 1, 2020
PubMed

Insights

Interleukin-6 (IL-6) inhibition may prevent cardiovascular diseases like coronary artery disease (CAD) and atrial fibrillation (AF). However, increased Interleukin-1 receptor antagonist (IL-1ra) levels may raise the risk for CAD and cardioembolic stroke.

Area of Science:

  • Genetics
  • Immunology
  • Cardiovascular Medicine

Background:

  • The precise role of interleukins (ILs) in cardiovascular disease pathogenesis remains unclear.
  • Investigating the causal links between circulating ILs and major cardiovascular outcomes is crucial for therapeutic development.

Purpose of the Study:

  • To explore the associations between genetically predicted circulating levels of various interleukins and the risk of coronary artery disease (CAD), atrial fibrillation (AF), and ischemic stroke.
  • To elucidate the specific causal roles of different ILs in cardiovascular disease development.

Main Methods:

  • A Mendelian randomization study design was employed.
  • Genome-wide association studies identified single-nucleotide polymorphisms (SNPs) associated with IL-1β, IL-1 receptor antagonist (IL-1ra), IL-2 receptor subunit alpha, IL-6, IL-16, IL-17, and IL-18.
  • Summary-level genetic data from large consortia were used for outcome association analyses.

Main Results:

  • Genetically elevated IL-1ra levels showed a significant association with increased CAD risk (OR=1.36).
  • Genetically elevated IL-6 levels, particularly those associated with reduced bio-function, were inversely associated with CAD (OR=0.64) and AF (OR=0.70).
  • Suggestive associations were observed for IL-1ra with cardioembolic stroke and IL-6 with various ischemic stroke subtypes; IL-16 showed a suggestive inverse association with CAD.

Conclusions:

  • Findings support IL-6 inhibition as a potential therapeutic strategy for preventing CAD, AF, and ischemic stroke.
  • Elevated IL-1ra levels suggest a potential increased risk for CAD and cardioembolic stroke, indicating a possible detrimental role of IL-1 pathway activation.
  • The association of IL-16 with CAD warrants further investigation.
Abstract

Keywords:
Atrial fibrillationCoronary artery diseaseImmuneInterleukinsIschemic strokeMendelian randomization analysis

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