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Published on: July 20, 2022
Causal relationship between osteoarthritis with atrial fibrillation and coronary atherosclerosis: a bidirectional
Meng Yin1, Wenchang Xu2,3, Jixiang Pang4
1Shandong Academy of Occupational Health and Occupational Medicine, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, China.
Insights
Osteoarthritis (OA) increases the risk of atrial fibrillation (AF). However, osteoarthritis and coronary atherosclerosis (CA) appear to have a mutually protective relationship, suggesting complex cardiovascular interactions.
Area of Science:
- Genetics and Epidemiology
- Cardiovascular Medicine
- Rheumatology
Background:
- Osteoarthritis (OA) is a prevalent degenerative condition.
- Observational studies suggest a link between OA and cardiovascular diseases (CVD), including atrial fibrillation (AF) and coronary atherosclerosis (CA).
- Robust evidence confirming the OA-CVD association is limited.
Purpose of the Study:
- To investigate the causal relationship between osteoarthritis and cardiovascular diseases, specifically atrial fibrillation and coronary atherosclerosis.
- To utilize a bidirectional two-sample Mendelian randomization approach to assess these associations.
Main Methods:
- A bidirectional two-sample Mendelian randomization study was conducted.
- Data for OA were integrated from UK Biobank and arcogen (n=417,596).
- Data for AF (n=1,030,836) and CA (n=218,792) were obtained from large-scale genetic studies.
- Inverse variance weighted (IVW) method was the primary analysis, supplemented by MR Egger and weighted median methods. Sensitivity analyses included Cochran Q statistic and leave-one-out analysis.
Main Results:
- Osteoarthritis was found to be a risk factor for atrial fibrillation (IVW: OR 1.11, P=0.002).
- A negative association was observed between osteoarthritis and coronary atherosclerosis (IVW: OR 0.88, P=0.02).
- Reverse analyses indicated no significant effect of AF on OA, but confirmed a negative association between CA and OA (IVW: OR 0.95, P=0.01).
Conclusions:
- This study provides genetic evidence that osteoarthritis is a risk factor for atrial fibrillation.
- A mutually protective relationship exists between osteoarthritis and coronary atherosclerosis.
- Further research is needed to elucidate the underlying biological mechanisms driving these associations.
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 (n = 417,596), AF data were obtained from six studies (n = 1,030,836), and coronary atherosclerosis data were derived from the FinnGen (n = 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), P = 0.002], while OA and CA were negatively associated [IVW: OR (95% CI): 0.88 (0.79, 0.98), P = 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), P = 0.84], meanwhile, CA and OA were found to be associated negatively [IVW: OR (95% CI): 0.95 (0.92, 0.99), P = 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.
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