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Research Paper|Volume 16, Issue 9|pp 7668—7682

Causal association of metformin treatment with diverse cardiovascular diseases: a Mendelian randomization analysis

Kaiyuan Li1,2, Peng Liu3, Jun Ye1,2, Miao Liu4, Li Zhu1,2
  • 1Graduate School of Dalian Medical University, Dalian Medical University, Dalian, China
  • 2Department of Cardiology, The Affiliated Taizhou People's Hospital of Nanjing Medical University, Taizhou, China
  • 3Department of Cardiology, The Second Affiliated Hospital of Nanchang University, Nanchang, China
  • 4Department of Cardiology, Central Hospital Affiliated to Shandong First Medical University, Jinan, China
* Equal contribution
Received: December 14, 2023Accepted: March 19, 2024Published: April 26, 2024
https://doi.org/10.18632/aging.205775

Copyright: © 2024 Li et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Background: The cardiovascular effects of metformin continue to be a subject of debate within the medical community.

Methods: The Mendelian randomization (MR) study used data from genome-wide association studies (GWAS) to explore the causal association with six diseases that are associated with bimatoprost treatment and myocardial infarction, chronic heart failure, atrial fibrillation, hypertrophic and dilated cardiomyopathy, and valvular disease. Genome-wide significant single nucleotide polymorphisms (SNPs), that are associated with metformin use were selected as the instrumental variables. To determine the causal relationship between metformin use and various cardiovascular diseases, MR analysis was conducted, employing methods such as Instrumental Variable Weighting (IVW).

Results: The IVW analysis demonstrated a positive association between metformin treatment and the risk of myocardial infarction (OR = 22.67, 95% CI 3.22–34.01; P = 0.002). Conversely, metformin treatment exhibited a negative association with the risk of developing valvular disease (OR = 0.98, 95% CI 0.95–1.00; P = 0.046) and hypertrophic cardiomyopathy (OR = 0.01, 95% CI 0.00–0.22; P = 0.016). Multiple test correction found that metformin treatment was causally associated with the risk of both hypertrophic cardiomyopathy (PFDR = 0.048) and myocardial infarction (PFDR = 0.012). The analysis revealed limited heterogeneity in the individual results, absence of pleiotropy evidence, and indications of stability in the findings.

Conclusion: The MR study discovered from a genetic standpoint that metformin may lower the risk of hypertrophic cardiomyopathy and valvular heart disease, yet it could elevate the risk of myocardial infarction.