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Plasma Cortisol and Risk of Atrial Fibrillation: A Mendelian Randomization Study

Susanna C Larsson1,2, Wei-Hsuan Lee3, Stephen Burgess3,4

  • 1Unit of Cardiovascular and Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.

The Journal of Clinical Endocrinology and Metabolism
|April 6, 2021
PubMed

Insights

High cortisol levels increase atrial fibrillation risk, likely through effects on blood pressure and waist circumference. This study used Mendelian randomization to investigate the causal link between cortisol and AF. Further research is needed to confirm these findings.

Area of Science:

  • Endocrinology
  • Cardiology
  • Genetics

Background:

  • Atrial fibrillation (AF) and cardiac arrhythmias are prevalent in patients with Cushing's syndrome (chronic hypercortisolism).
  • A causal link between hypercortisolism and AF remains unestablished.

Purpose of the Study:

  • To investigate the causal association between plasma cortisol levels and atrial fibrillation risk.
  • Utilizing a two-sample Mendelian randomization (MR) design to assess causality.

Main Methods:

  • Employed genetic variants functionally linked to plasma cortisol from the CORtisol NETwork consortium.
  • Analyzed genome-wide association study (GWAS) data for AF from multiple large cohorts (FinnGen, UK Biobank).
  • Conducted multivariable MR to evaluate mediation by systolic blood pressure (SBP) and waist circumference (WC).

Main Results:

  • A one-SD increase in genetically predicted plasma cortisol was associated with a 20% increased risk of AF (OR 1.20).
  • This association was attenuated when adjusting for genetically predicted SBP and WC (OR 0.99), suggesting mediation.

Conclusions:

  • Mendelian randomization provides evidence for a positive causal association between plasma cortisol and AF risk.
  • Systolic blood pressure and waist circumference may act as mediating factors in this relationship.
Abstract

Keywords:
Atrial fibrillationCushing’s syndromeMendelian randomizationcortisol

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