Relationship between rheumatoid arthritis and cardiovascular comorbidity, causation or co-occurrence: A Mendelian randomization study

Min Wang; Ce Chao; Kun Mei; Dongmei Di; Yongxiang Qian; Bin Wang; Xiaoying Zhang

doi:10.3389/fcvm.2023.1099861

Relationship between rheumatoid arthritis and cardiovascular comorbidity, causation or co-occurrence: A Mendelian randomization study

Front Cardiovasc Med. 2023 Mar 17:10:1099861. doi: 10.3389/fcvm.2023.1099861. eCollection 2023.

Authors

Min Wang¹, Ce Chao¹, Kun Mei¹, Dongmei Di¹, Yongxiang Qian¹, Bin Wang¹, Xiaoying Zhang¹

Affiliation

¹ Department of Cardiothoracic Surgery, The Third Affiliated Hospital of Soochow University, Changzhou, China.

Abstract

Background: In recent years, the incidence rates of rheumatoid arthritis (RA) and heart disease (HD) have noticeably increased worldwide. Previous studies have found that patients with RA are more likely to develop HD, while the cause and effect have still remained elusive. In this study, Mendelian randomization (MR) analysis was used to indicate whether there was a potential association between RA and HD.

Methods: Data of RA, ischemic heart disease (IHD), myocardial infarction (MI), atrial fibrillation (AF), and arrhythmia were based on the genome-wide association study (GWAS) dataset. No disease group was intersected. Inverse-variance weighted (IVW) method was used to calculate MR estimates, and sensitivity analysis was performed.

Results: The primary MR analysis showed that genetic susceptibility to RA was significantly associated with the risk of IHD and MI, rather than with AF and arrhythmia. Besides, there was no heterogeneity and horizontal pleiotropy between the primary and replicated analyses. There was a significant correlation between RA and the risk of IHD (odds ratio (OR), 1.0006; 95% confidence interval (CI), 1.000244-1.00104; P = 0.001552), meanwhile, there was a significant correlation between RA and the risk of MI (OR, 1.0458; 95% CI, 1.07061-1.05379; P = 0.001636). The results were similar to those of sensitivity analysis, and the sensitivity analysis also verified the conclusion. Furthermore, sensitivity and reverse MR analyses suggested that no heterogeneity, horizontal pleiotropy or reverse causality was found between RA and cardiovascular comorbidity.

Conclusion: RA was noted to be causally associated with IHD and MI, rather than with AF and arrhythmia. This MR study might provide a new genetic basis for the causal relationship between RA and the risk of CVD. The findings suggested that the control of RA activity might reduce the risk of cardiovascular disease.

Keywords: Mendelian randomization analysis; arrhythmia; atrial fibrillation; genome-wide association study; ischemic heart disease; myocardial infarction; rheumatoid arthritis.

Grants and funding

This study was financially supported by the Young Talent Development Plan of Changzhou Health Commission (grant nos. CZQM2020034 and CZQM2020004), Young Talent Science and Technology Project of Changzhou Health Commission (grant no. QN201913), and Social Development Projects of Changzhou Science and Technology Bureau (grant no. CE20205039).