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Causal associations of insulin resistance with coronary artery disease and ischemic stroke: a Mendelian randomization

Weiqi Chen1,2, Shukun Wang3, Wei Lv2

  • 1Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.

BMJ Open Diabetes Research & Care
|May 14, 2020
PubMed

Insights

Insulin resistance (IR) causally increases the risk of coronary artery disease, myocardial infarction, and ischemic stroke. This Mendelian randomization study clarifies the link between IR and cardiovascular disease development.

Area of Science:

  • Genetics
  • Cardiovascular Medicine
  • Metabolic Disorders

Background:

  • The causal relationship between insulin resistance (IR) and cardiovascular diseases (CVDs) remains incompletely understood.
  • Existing research has not definitively established whether IR directly contributes to the development of various CVDs.

Purpose of the Study:

  • To investigate the causal associations between insulin resistance and major cardiovascular diseases.
  • To examine the specific links between IR and coronary artery disease, myocardial infarction, and ischemic stroke subtypes using a robust genetic approach.

Main Methods:

  • Employed Mendelian randomization (MR) analysis utilizing 53 single nucleotide polymorphisms associated with IR phenotypes as instrumental variables.
  • Leveraged large-scale genome-wide association study (GWAS) summary statistics from European ancestry cohorts for both IR phenotypes and cardiovascular outcomes.
  • Applied inverse-variance weighted, simple, and weighted-median MR approaches, with MR-Egger regression to assess pleiotropy.

Main Results:

  • A one-standard deviation increase in genetically predicted IR was significantly associated with increased risk for coronary artery disease (OR=1.79), myocardial infarction (OR=1.78), and ischemic stroke (OR=1.21).
  • The association was particularly strong for the small-artery occlusion subtype of ischemic stroke (OR=1.80).
  • No significant causal associations were found for large-artery atherosclerosis or cardioembolism stroke subtypes. Sensitivity analyses confirmed the robustness of the findings, with no evidence of significant pleiotropy.

Conclusions:

  • This study provides strong genetic evidence supporting a causal role of insulin resistance in the development of coronary artery disease, myocardial infarction, and ischemic stroke.
  • Specifically, IR is implicated in the pathogenesis of the small-artery occlusion subtype of stroke.
  • These findings underscore the importance of managing insulin resistance for cardiovascular disease prevention.
Abstract

Keywords:
coronary artery diseasegeneticsinsulin resistancestroke

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