Abstract
Significant genetic association exists between rheumatoid arthritis (RA) and cardiovascular disease. The associated mechanisms include common inflammatory mediators, changes in lipoprotein composition and function, immune responses, etc. However, the causality of RA and vascular/heart problems remains unknown. Herein, we performed Mendelian randomization (MR) analysis using a large-scale RA genome-wide association study (GWAS) dataset (462,933 cases and 457,732 controls) and six cardio-cerebrovascular disease GWAS datasets, including age angina (461,880 cases and 447,052 controls), hypertension (461,880 cases and 337,653 controls), age heart attack (10,693 cases and 451,187 controls), abnormalities of heartbeat (461,880 cases and 361,194 controls), stroke (7,055 cases and 454,825 controls), and coronary heart disease (361,194 cases and 351,037 controls) from United Kingdom biobank. We further carried out heterogeneity and sensitivity analyses. We confirmed the causality of RA with age angina (OR = 1.17, 95% CI: 1.04–1.33, p = 1.07E−02), hypertension (OR = 1.45, 95% CI: 1.20–1.75, p = 9.64E−05), age heart attack (OR = 1.15, 95% CI: 1.05–1.26, p = 3.56E−03), abnormalities of heartbeat (OR = 1.07, 95% CI: 1.01–1.12, p = 1.49E−02), stroke (OR = 1.06, 95% CI: 1.01–1.12, p = 2.79E−02), and coronary heart disease (OR = 1.19, 95% CI: 1.01–1.39, p = 3.33E−02), contributing to the understanding of the overlapping genetic mechanisms and therapeutic approaches between RA and cardiovascular disease.
Highlights
Cardiovascular disease remains the leading cause of human death, with an estimated 17.3 million people worldwide dying of cardiovascular disease each year, which is expected to increase to 23.6 million by 2030 (Laslett et al, 2012; Smith et al, 2012; Leong et al, 2017)
Epidemiological studies have shown that the occurrence of cardiovascular disease is caused by various factors, with obesity, diabetes, smoking, hyperlipidemia, atherosclerosis, hypertension, and blood viscosity being its potential risk factor (Leong et al, 2017; Xu et al, 2019)
Traditional cardiovascular disease risk factors account for a large proportion of rheumatoid arthritis (RA) (An et al, 2016)
Summary
Cardiovascular disease remains the leading cause of human death, with an estimated 17.3 million people worldwide dying of cardiovascular disease each year, which is expected to increase to 23.6 million by 2030 (Laslett et al, 2012; Smith et al, 2012; Leong et al, 2017). Most of the previous studies have examined the association between RA and atherosclerosis and congestive heart. Rheumatoid Arthritis and Cardiovascular Disease failure, ignoring other phenotypes of heart disease and vascular problems (England et al, 2018). Mendelian randomization (MR) could estimate causality without bias, which has been used in previous studies to explore the association between phenotypes (Jansen et al, 2014; Smith et al, 2017; Hemani et al, 2018; Cheng et al, 2019b, 2021; Zhuang et al, 2019; Qiu et al, 2021). We provided strong evidence that RA contributed to six vascular-/heart problem-related phenotypes, which could be of great significance for clinical disease prevention and treatment
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