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

Qiong Nie; Qiang Luo; Wei Yan; Tongtong Zhang; Han Wang; Jing Wu

doi:10.3389/fcvm.2023.1033644

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

Front Cardiovasc Med. 2023 Apr 28:10:1033644. doi: 10.3389/fcvm.2023.1033644. eCollection 2023.

Authors

Qiong Nie¹, Qiang Luo², Wei Yan¹, Tongtong Zhang³, Han Wang², Jing Wu¹

Affiliations

¹ Department of Geriatrics, The Affiliated Hospital of Southwest Jiaotong University, The Third People's Hospital of Chengdu, Chengdu, China.
² Department of Cardiology, The Affiliated Hospital of Southwest Jiaotong University, The Third People's Hospital of Chengdu, Chengdu, China.
³ Department of General Surgery, The Center of Gastrointestinal and Minimally Invasive Surgery, The Affiliated Hospital of Southwest Jiaotong University, The Third People's Hospital of Chengdu, Chengdu, China.

Abstract

Objectives: The relationship between rheumatoid arthritis (RA) and coronary atherosclerosis is widely concerned, but observational studies have not clarified causality. We performed two-sample Mendelian randomization (MR) study to assess the causal association between RA and coronary atherosclerosis.

Methods: we mainly conducted MR analysis using the inverse variance weighted (IVW) approach. Weighted median, MR-Egger regression and maximum likelihood were conducted as sensitivity analyses for supplementary analysis. Multivariate MR also were performed to validate the results of two-sample MR. Furthermore, we performed the MR-Egger intercept, MR-PRESSO, Cochran's Q test, and "Leave-one-out" to assess the levels of pleiotropy and heterogeneity.

Results: IVW result showed a positive link between genetic predisposition to RA and increased relative risk of coronary atherosclerosis (OR: 1.0021, 95%CI 1.0011-1.0031, P < 0.05). The result was confirmed by the weighted median method (OR: 1.0028, 95%CI 1.0014-1.0042, P < 0.05), MR-Egger regression (OR: 1.0031, 95%CI 1.0012-1.0049, P < 0.05) and maximum likelihood (OR: 1.0021, 95%CI 1.0011-1.0030, P < 0.05). Multivariate MR also reached a consistent conclusion. In addition, MR-Egger intercept (P = 0.20) and MR-PRESSO (P = 0.06) did not provide evidence of horizontal pleiotropy. Meanwhile, the results of Cochran's Q test (P = 0.05) and "Leave-one-out" failed to detect significant heterogeneity.

Conclusion: The result of the two-sample MR analysis found genetic evidence to support the positive causal association between RA and coronary atherosclerosis, suggesting that active intervention for RA may reduce the incidence of coronary atherosclerosis.

Keywords: causation; coronary atherosclerosis; genome-wide-association studies; mendelian randomization; rheumatoid arthritis.