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Meta-Analysis
. 2025 May;137(9-10):272-278.
doi: 10.1007/s00508-024-02392-8. Epub 2024 Jul 26.

Genetic relationship between rheumatoid arthritis and cardiovascular diseases : A systematic review of Mendelian randomization studies

Mathias Ausserwinkler  1   2 , Sophie Gensluckner  2 , Andreas Voelkerer  3 , Jens Thiel  4   5 , Hans-Jörg Neumann  1 , Maria Flamm  6 , Christian Datz  3 , Elmar Aigner  2 , Bernhard Wernly  7   8
Affiliations
Meta-Analysis

Genetic relationship between rheumatoid arthritis and cardiovascular diseases : A systematic review of Mendelian randomization studies

Mathias Ausserwinkler et al. Wien Klin Wochenschr. 2025 May.

Abstract

Objective: Rheumatoid arthritis (RA) is recognized as a chronic autoimmune disorder with systemic inflammation and joint damage. Its potential role as a risk factor for cardiovascular diseases (CVD) is increasingly noted. This review delves into the causal relationship between RA and CVD, with Mendelian randomization (MR) offering a genetic perspective.

Methods: An extensive search was conducted in PubMed, Cochrane and Web of Science to identify MR studies addressing the RA-CVD link. Out of 530 studies, 9 met the inclusion criteria, which were rigorously assessed using a critical appraisal checklist. These were further stratified by a sensitivity analysis into categories reflecting the strength of their evidence, from not evaluable to robust.

Results: From the nine included studies, eight supported a causal association between RA and an increased risk of CVD, specifically coronary artery disease (CAD) and one did not support a link between RA and heart failure. The results suggest that genetic factors associated with RA may contribute to an elevated risk for CVD. Chronic inflammation, prevalent in RA, emerges as a key mediator in this connection.

Conclusion: The systematic review corroborates a genetic causal link between RA and CVD, as evidenced by eight of the nine MR studies reviewed. This suggests a need for integrated cardiovascular risk management in the treatment of RA patients. The findings advocate considering anti-inflammatory treatment that can reduce cardiovascular risk. The overarching evidence signifies a potential direction for new therapeutic strategies aimed at enhancing cardiovascular health in RA patients.

Keywords: Cardiovascular diseases; Chronic inflammation; Genetic causality; Inflammatory joint disease; Mendelian randomization; Rheumatoid arthritis.

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Conflict of interest statement

Conflict of interest: M. Ausserwinkler, S. Gensluckner, A. Voelkerer, J. Thiel, H. Neumann, M. Flamm, C. Datz, E. Aigner and B. Wernly declare that they have no conflict of interests.

Figures

Fig. 1
Fig. 1
The PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) serves as a visual guide to transparently depict the selection process for the studies in the systematic review
See this image and copyright information in PMC

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