Department of Cardiology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, CN.
Department of Cardiology, Shanghai East Hospital of Clinical Medical College, Dalian Medical University, Dalian, CN.
Glob Heart. 2023 Aug 11;18(1):43. doi: 10.5334/gh.1256. eCollection 2023.
Evidence from observational epidemiological studies indicated that rheumatoid arthritis (RA) increased the risk of heart failure (HF). However, there is a possibility that the correlation is not explained as a causative role for RA in the pathogenesis of HF. A two-sample Mendelian randomization (MR) framework was designed to explore the potential etiological role of RA in HF to identify the target to improve the burden of HF disease.
To assess the causal association between RA and HF, we analyzed summary statistics from genome-wide association studies (GWASs) for individuals of European descent. Genetic instruments for RA were identified at a genome-wide significance threshold (p < 5 × 10). Corresponding data were obtained from a GWAS meta-analysis (95,524 cases and 1,270,968 controls) to identify genetic variants underlying HF. MR estimates were pooled using the inverse variance weighted method. Complementary analyses were conducted to assess the robustness of the results.
There was no evidence of a causal association between genetically predicted RA and HF [odds ratio (OR), 1.00; 95% confidence interval (CI), 0.99-1.02; = 0.60]. Various sensitivity analyses suggested no pleiotropy detected (all > 0.05).
Our findings did not support the causal role of RA in the etiology of HF. As such, therapeutics targeted at the control of RA may have a lower likelihood of effectively controlling the occurrence of HF.
来自观察性流行病学研究的证据表明类风湿关节炎（RA）会增加心力衰竭（HF）的风险。然而，RA 在 HF 发病机制中起因果作用的这种相关性并不能得到解释。本研究采用两样本 Mendelian 随机化（MR）框架，旨在探索 RA 导致 HF 的潜在病因学作用，以确定改善 HF 疾病负担的靶点。
为了评估 RA 与 HF 之间的因果关系，我们分析了欧洲血统个体的全基因组关联研究（GWAS）的汇总统计数据。在全基因组显著阈值（p < 5 × 10）下确定 RA 的遗传工具。通过 GWAS 荟萃分析（95524 例病例和 1270968 例对照）获得 HF 潜在遗传变异的相应数据。使用逆方差加权法汇总 MR 估计值。进行了补充分析以评估结果的稳健性。
遗传预测的 RA 与 HF 之间没有因果关系的证据[比值比（OR），1.00；95%置信区间（CI），0.99-1.02；P = 0.60]。各种敏感性分析表明未检测到混杂（所有 P > 0.05）。
我们的研究结果不支持 RA 在 HF 发病机制中的因果作用。因此，针对 RA 控制的治疗方法不太可能有效控制 HF 的发生。
