BackgroundIn 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.MethodsData 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.ResultsThe 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.ConclusionRA 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.

中文翻译：

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类风湿性关节炎与心血管合并症、因果关系或共现之间的关系：一项孟德尔随机研究

背景近年来，类风湿性关节炎（RA）和心脏病（HD）的发病率在世界范围内显着增加。先前的研究发现，RA 患者更容易发展为 HD，但其因果关系仍不清楚。在这项研究中，使用孟德尔随机化 (MR) 分析来表明 RA 和 HD 之间是否存在潜在关联。基于全基因组关联研究 (GWAS) 数据集。没有疾病组被交叉。使用逆方差加权 (IVW) 方法计算 MR 估计值，并进行敏感性分析。结果初步 MR 分析表明，RA 的遗传易感性与 IHD 和 MI 的风险显着相关，而不是与 AF 和心律失常相关。此外，主要分析和重复分析之间没有异质性和水平多效性。RA 与 IHD 风险之间存在显着相关性（比值比 (OR)，1.0006；95% 置信区间 (CI)，1.000244–1.00104；P= 0.001552），同时，RA 与 MI 风险之间存在显着相关性（OR，1.0458；95% CI，1.07061–1.05379；P= 0.001636）。结果与敏感性分析相似，敏感性分析也验证了结论。此外，敏感性和反向 MR 分析表明，在 RA 和心血管合并症之间没有发现异质性、水平多效性或反向因果关系。结论 RA 与 IHD 和 MI 有因果关系，而不是 AF 和心律失常。这项 MR 研究可能为 RA 与 CVD 风险之间的因果关系提供新的遗传基础。研究结果表明，控制 RA 活动可能会降低心血管疾病的风险。