骨关节炎与心房颤动和冠状动脉粥样硬化之间的因果关系：一项针对欧洲血统人群的双向孟德尔随机化研究。

Causal relationship between osteoarthritis with atrial fibrillation and coronary atherosclerosis: a bidirectional Mendelian randomization study of European ancestry.

作者信息

Yin Meng, Xu Wenchang, Pang Jixiang, Xie Siwen, Xiang Mengting, Shi Bin, Fan Hua, Yu Gongchang

机构信息

Shandong Academy of Occupational Health and Occupational Medicine, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, China.

School of Acupuncture and Tuina, Shandong University of Traditional Chinese Medicine, Jinan, China.

出版信息

Front Cardiovasc Med. 2023 Jul 31;10:1213672. doi: 10.3389/fcvm.2023.1213672. eCollection 2023.

BACKGROUND

Osteoarthritis (OA) is a degenerative disease with high prevalence. Some observational studies have shown that patients with osteoarthritis often have co-existing cardiovascular diseases (CVD) such as atrial fibrillation (AF) and coronary atherosclerosis (CA). However, there is still a lack of stronger evidence confirming the association between osteoarthritis and cardiovascular disease. In this study, we used a bidirectional two-sample Mendelian randomization study to investigate the relationship between OA with AF and CA.

METHODS

OA data from the UK Biobank and arcOGEN (Arthritis Research UK Osteoarthritis Genetics, a study that aimed to find genetic determinants of osteoarthritis and elucidate the genetic architecture of the disease) integration were selected for the study ( = 417,596), AF data were obtained from six studies ( = 1,030,836), and coronary atherosclerosis data were derived from the FinnGen ( = 218,792). MR analysis was performed primarily using the Inverse variance weighted (IVW) method, with MR Egger, weighted median, simple mode, weighted mode as supplements, sensitivity analysis was performed using Cochran Q statistic, and leave-one-out analysis.

RESULTS

We found that OA and AF were positively associated [IVW: OR (95% CI): 1.11 (1.04, 1.19), = 0.002], while OA and CA were negatively associated [IVW: OR (95% CI): 0.88 (0.79, 0.98), = 0.02]. In the reverse MR analysis, no effect of AF on OA was found [IVW: OR (95% CI): 1.00 (0.97, 1.03), = 0.84], meanwhile, CA and OA were found to be associated negatively [IVW: OR (95% CI): 0.95 (0.92, 0.99), = 0.01]. No violations of MR assumptions were found in the sensitivity analysis.

CONCLUSION

This research confirms that OA is a risk factor for AF, and there is a mutual protective factor between OA and CA. However, further studies are still necessary to elucidate the underlying mechanisms.

背景

骨关节炎（OA）是一种高发性退行性疾病。一些观察性研究表明，骨关节炎患者常并存心血管疾病（CVD），如心房颤动（AF）和冠状动脉粥样硬化（CA）。然而，仍缺乏更强有力的证据证实骨关节炎与心血管疾病之间的关联。在本研究中，我们采用双向双样本孟德尔随机化研究来探究骨关节炎与心房颤动和冠状动脉粥样硬化之间的关系。

方法

本研究选取了来自英国生物银行和arcOGEN（英国关节炎研究骨关节炎遗传学，一项旨在寻找骨关节炎的遗传决定因素并阐明该疾病遗传结构的研究）整合后的骨关节炎数据（n = 417,596），从六项研究中获取心房颤动数据（n = 1,030,836），并从芬兰基因库获取冠状动脉粥样硬化数据（n = 218,792）。主要采用逆方差加权（IVW）方法进行孟德尔随机化分析，以MR-Egger、加权中位数、简单模式、加权模式作为补充，使用Cochran Q统计量进行敏感性分析，并进行留一法分析。

结果

我们发现骨关节炎与心房颤动呈正相关[IVW：比值比（95%置信区间）：1.11（1.04，1.19），P = 0.002]，而骨关节炎与冠状动脉粥样硬化呈负相关[IVW：比值比（95%置信区间）：0.88（0.79，0.98），P = 0.02]。在反向孟德尔随机化分析中，未发现心房颤动对骨关节炎有影响[IVW：比值比（95%置信区间）：1.00（0.97，1.03），P = 0.84]，同时发现冠状动脉粥样硬化与骨关节炎呈负相关[IVW：比值比（95%置信区间）：0.95（0.92，0.99），P = 0.01]。敏感性分析未发现违反孟德尔随机化假设的情况。