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Causal Relationships Between Gastroesophageal Reflux Disease and Myocardial Infarction: Insights From Univariable and

Xiaoya Zheng1, Teng Hu2, Tianxiang Fang1

  • 1Health Science Center, Ningbo University, Ningbo, China.

Annals of Human Genetics
|July 28, 2025
PubMed

Insights

Gastroesophageal reflux disease (GERD) is causally linked to myocardial infarction (MI). Hypertension and type-2 diabetes mellitus significantly mediate this association, suggesting improved cardiometabolic monitoring for GERD patients.

Area of Science:

  • Cardiovascular Epidemiology
  • Gastroenterology
  • Genetic Epidemiology

Background:

  • Observational studies suggest a link between gastroesophageal reflux disease (GERD) and myocardial infarction (MI).
  • Causality and confounding factors in the GERD-MI relationship require further investigation.
  • Understanding mediating factors is crucial for clinical management.

Purpose of the Study:

  • To investigate the causal relationship between GERD and MI using Mendelian randomization.
  • To identify and quantify the mediating effects of cardiovascular risk factors in the GERD-MI pathway.
  • To inform clinical strategies for mitigating MI risk in GERD patients.

Main Methods:

  • Two-sample Mendelian randomization (MR) analyses utilizing large-scale genome-wide association study data for GERD and MI.
  • Multivariable MR to assess the independent effect of GERD on MI risk, adjusting for confounders.
  • Two-step MR to investigate mediation pathways involving modifiable risk factors.

Main Results:

  • A significant causal association was found between GERD and MI (OR=1.61, P < 10^-26).
  • This association persisted after adjusting for body mass index, smoking, and alcohol consumption.
  • Hypertension (14.4% mediation) and type-2 diabetes mellitus (12.0% mediation) were identified as significant mediators.

Conclusions:

  • Modifiable cardiovascular risk factors, particularly hypertension and type-2 diabetes mellitus, mediate the causal link between GERD and MI.
  • Integrated cardiometabolic monitoring is clinically important for GERD patients.
  • Targeted management of blood pressure and glycemic control may reduce MI risk in individuals with GERD.
Abstract

Keywords:
Mendelian randomizationcardiometabolic factorsgastroesophageal reflux diseasemediatorsmyocardial infarction

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