Table3_Association of ankylosing spondylitis with cardiovascular disease: a bidirectional two-sample mendelian randomization study.DOCX

BackgroundsCurrent observational investigations hint at a potential linkage between ankylosing spondylitis and cardiovascular wellness. However, the nature of this causality remains to be elucidated. Consequently, this study is designed to evaluate the causal interconnection between ankylosing spondylitis and cardiovascular-related conditions utilizing a bidirectional two-sample Mendelian Randomization (MR) methodology.
MethodsIn this study, we conducted Mendelian randomization (MR) analyses using genome-wide association study (GWAS) data. The fixed-effects inverse variance weighted (IVW) model was used as the primary analysis method, and MR-Egger regression and the weighted median method were employed as supplementary approaches. Horizontal pleiotropy and heterogeneity were evaluated using various statistical tests, including MR-PRESSO global test, MR-Egger intercept, and Cochran’s Q test.
ResultsThe MR result demonstrated an increased risk of heart failure in individuals with ankylosing spondylitis (OR: 1.0132, 95% CI = 1.0043-1.0221, p = 0.003). The MR analysis results did not demonstrate a causal relationship between ankylosing spondylitis and other cardiovascular diseases, such as atrial fibrillation, coronary artery disease, ischemic stroke, myocardial infarction, and valvular heart disease (all p > 0.05). No evidence of reverse causality was found between ankylosing spondylitis and mentioned cardiovascular diseases in reverse MR analyses. Sensitivity analysis verified the reliability of the results.
ConclusionOur MR study indicates a relationship between ankylosing spondylitis and an increased risk of heart failure. Further research is needed to confirm these findings and elucidate the underlying mechanisms involved.

研究背景：当前观察性研究提示，强直性脊柱炎（ankylosing spondylitis）与心血管健康之间可能存在关联。然而，二者间的因果关系本质仍有待阐明。为此，本研究采用双向两样本孟德尔随机化（bidirectional two-sample Mendelian Randomization, MR）方法，旨在评估强直性脊柱炎与心血管相关疾病之间的因果关联。

研究方法：本研究利用全基因组关联研究（genome-wide association study, GWAS）数据开展孟德尔随机化（MR）分析。以固定效应逆方差加权（fixed-effects inverse variance weighted, IVW）模型作为主要分析方法，并辅以MR-Egger回归与加权中位数法作为补充分析手段。通过MR-PRESSO全局检验、MR-Egger截距检验及Cochran Q检验等多种统计学方法，评估水平多效性与研究异质性。

研究结果：MR分析结果显示，强直性脊柱炎患者发生心力衰竭的风险升高（比值比（odds ratio, OR）=1.0132，95%置信区间（confidence interval, CI）=1.0043~1.0221，p=0.003）。未发现强直性脊柱炎与其他心血管疾病（包括心房颤动、冠状动脉疾病、缺血性脑卒中、心肌梗死及瓣膜性心脏病）之间存在因果关联（所有p>0.05）。反向MR分析未发现强直性脊柱炎与上述心血管疾病之间存在反向因果关系。敏感性分析验证了本研究结果的可靠性。

研究结论：本MR研究表明，强直性脊柱炎与心力衰竭风险升高存在关联。未来仍需开展进一步研究以验证该发现，并阐明其潜在的作用机制。