Rheumatoid arthritis and coronary atherosclerosis: a two-sample Mendelian randomization study

Area of Science:

• Cardiovascular Epidemiology
• Rheumatology
• Genetic Epidemiology

Background:

• Observational studies suggest a link between rheumatoid arthritis (RA) and coronary atherosclerosis but have not established causality.
• Understanding the causal relationship is crucial for developing effective prevention strategies for cardiovascular disease in RA patients.

Purpose of the Study:

• To investigate the potential causal association between rheumatoid arthritis (RA) and coronary atherosclerosis using a two-sample Mendelian randomization (MR) approach.
• To provide robust genetic evidence to clarify the etiological link between RA and coronary atherosclerosis.

Main Methods:

• Employed a two-sample Mendelian randomization (MR) study design.
• Utilized the inverse variance weighted (IVW) method as the primary analysis, with weighted median, MR-Egger regression, and maximum likelihood for sensitivity analyses.
• Performed multivariate MR and assessed pleiotropy and heterogeneity using MR-Egger intercept, MR-PRESSO, Cochran's Q test, and Leave-one-out analyses.

Main Results:

• The IVW analysis revealed a significant positive causal association between genetic predisposition to RA and an increased risk of coronary atherosclerosis (OR: 1.0021, 95%CI 1.0011-1.0031, P < 0.05).
• Sensitivity analyses, including weighted median, MR-Egger regression, and maximum likelihood, consistently supported the positive association.
• No significant evidence of horizontal pleiotropy or substantial heterogeneity was detected, strengthening the validity of the findings.

Conclusions:

• This MR study provides strong genetic evidence for a positive causal relationship between rheumatoid arthritis and coronary atherosclerosis.
• Findings suggest that managing rheumatoid arthritis effectively may be a viable strategy to reduce the incidence of coronary atherosclerosis.