Inflammation and heart failure: a two-sample Mendelian randomization study

Sharon Remmelzwaal, Sabine van Oort, M Louis Handoko, Vanessa van Empel, Stephane R B Heymans, Joline W J Beulens

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

BACKGROUND: It is hypothesized that inflammation leads to heart failure. Results from observational studies thus far have been inconsistent and it is unclear whether inflammation is causally associated with new-onset heart failure. Mendelian randomization analyses are less prone to biases common in observational studies such as reverse causation and unmeasured confounding. The aim of this study was to investigate the causal relation between various inflammatory biomarkers with risk of new-onset heart failure by using a two-sample Mendelian randomization approach.

METHODS: Ten inflammatory biomarkers with available genome-wide association studies (GWAS) among individuals of European ancestry were identified and included C-reactive protein (CRP), immunoglobulin E, tumour necrosis factor (TNF), toll-like receptor 4, interleukin 1 receptor antagonist, interleukin 2 receptor subunit α, interleukin 6 receptor subunit α, interleukin 16, 17 and 18. For the associations between the identified SNPs and heart failure, we used the largest GWAS meta-analysis performed by the Heart Failure Molecular Epidemiology for Therapeutic Targets Consortium with 47 309 participants with heart failure and 930 014 controls. For our main analyses, we used the inverse-variance weighted method.

RESULTS: We included 63 SNPs. CRP, TNF, interleukin 2, 16 and 18 were not associated with heart failure with odds ratios (ORs) of 1.01 [95% confidence interval (95% CI: 0.94-1.09), 1.11 (95% CI: 0.80-1.48), 0.97 (95% CI: 0.93-1.02), 0.99 (95% CI: 0.96-1.03) and 1.01 (95% CI: 0.97-1.06), respectively. The other biomarkers were also not associated with the risk of heart failure and suffered from weak instrument bias.

CONCLUSION: This Mendelian randomization study could not determine a causal relationship between inflammation and risk of heart failure. However, some biomarkers suffered from weak instrument bias.

Original languageEnglish
Pages (from-to)728-735
Number of pages8
JournalJournal of Cardiovascular Medicine
Volume23
Issue number11
DOIs
Publication statusPublished - 1 Nov 2022

Keywords

  • Biomarkers
  • C-Reactive Protein/genetics
  • Genome-Wide Association Study
  • Heart Failure/epidemiology
  • Humans
  • Immunoglobulin E
  • Inflammation/genetics
  • Interleukin-16
  • Interleukin-2
  • Mendelian Randomization Analysis/methods
  • Polymorphism, Single Nucleotide
  • Receptors, Interleukin-1
  • Receptors, Interleukin-2
  • Receptors, Interleukin-6
  • Toll-Like Receptor 4
  • Tumor Necrosis Factors

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