Table7_Association of cardiovascular risk factors and lifestyle behaviors with aortic aneurysm: A Mendelian randomization study.XLSX

Objective: To examine the causality between hypertension, diabetes, other cardiovascular risk factors, lifestyle behaviors, and the aortic aneurysm among patients of European ancestry.
Methods: We performed two-sample Mendelian randomization (MR) analysis to investigate the causality of 12 modifiable risk factors with aortic aneurysm, including hypertension, body mass index (BMI), waist–hip ratio (WHR), diabetes, tobacco smoking, alcohol and coffee consumption, physical activity, and sleep duration. Genome-wide significant genetic instruments (p < 5 × 10–8) for risk factors were extracted from European-descent genome-wide association studies, whereas aortic aneurysm genetic instruments were selected from the UK Biobank and FinnGen cohort. The inverse-variance weighted MR was used as the main analysis, and MR-Egger (MRE), weighted median MR, MR pleiotropy residual sum and outlier, and Phenoscanner searching were performed as sensitivity analyses. Furthermore, we calculated MRE intercept to detect pleiotropy and Cochran’s Q statistics to assess heterogeneity and conducted bidirectional MR and MR Steiger tests to exclude the possibility of reverse causality.
Results: We observed significantly higher risks for the aortic aneurysm in hypertension [pooled OR: 4.30 (95% CI 2.84–6.52)], BMI [OR: 1.58 (95% CI 1.37–1.81)], WHR [OR: 1.51 (95% CI 1.21–1.88)], WHR adjusted for BMI (WHRadjBMI) [OR: 1.35 (95% CI 1.12–1.63)], age of smoking initiation [OR: 1.63 (95% CI 1.18–2.26)], and tobacco use (initiation, cessation, and heaviness) [OR: 2.88 (95% CI 1.85–2.26)]. In sensitivity analysis, the causal effects of hypertension, BMI, WHRadjBMI, and tobacco use (initiation, cessation, and heaviness) remained robust.
Conclusion: There was a positive causal relationship between hypertension, BMI, WHR, and WHRadjBMI and aortic aneurysm.

研究目的：系统解析欧洲血统人群中高血压、糖尿病、其他心血管危险因素、生活方式行为与主动脉瘤之间的因果关联。
方法：我们开展了双样本孟德尔随机化（two-sample Mendelian Randomization, MR）分析，以探究12种可修正危险因素与主动脉瘤的因果关系，涵盖高血压、体质指数（body mass index, BMI）、腰臀比（waist–hip ratio, WHR）、糖尿病、吸烟、饮酒与咖啡摄入、体力活动及睡眠时长。从欧洲血统人群的全基因组关联研究中提取危险因素的全基因组显著遗传工具（p < 5 × 10–8），而主动脉瘤的遗传工具则选自英国生物库（UK Biobank）与芬兰基因（FinnGen）队列。本研究以逆方差加权MR作为主要分析方法，并辅以MR-Egger（MRE）、加权中位数MR、MR多效性残差总和离群值分析及Phenoscanner检索作为敏感性分析手段。此外，我们通过计算MRE截距检测多效性，采用科克伦Q统计量（Cochran’s Q statistics）评估异质性，并开展双向MR与MR Steiger检验（MR Steiger tests）以排除反向因果的可能性。
结果：我们观察到，高血压[合并比值比（pooled OR）：4.30（95%置信区间：2.84~6.52）]、BMI[OR：1.58（95%置信区间：1.37~1.81）]、WHR[OR：1.51（95%置信区间：1.21~1.88）]、校正BMI的WHR（WHRadjBMI）[OR：1.35（95%置信区间：1.12~1.63）]、吸烟起始年龄[OR：1.63（95%置信区间：1.18~2.26）]及烟草使用（起始、戒断与负荷量）[OR：2.88（95%置信区间：1.85~2.26）]人群的主动脉瘤风险显著升高。敏感性分析结果显示，高血压、BMI、WHRadjBMI及烟草使用（起始、戒断与负荷量）的因果效应仍保持稳健。
结论：高血压、BMI、WHR及WHRadjBMI与主动脉瘤之间存在正向因果关联。