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心血管危险因素和生活方式行为与主动脉瘤的关联:一项孟德尔随机化研究。

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

作者信息

Zhou Jiawei, Lin Jianfeng, Zheng Yuehong

机构信息

Department of Vascular Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

出版信息

Front Genet. 2022 Aug 8;13:925874. doi: 10.3389/fgene.2022.925874. eCollection 2022.

Abstract

To examine the causality between hypertension, diabetes, other cardiovascular risk factors, lifestyle behaviors, and the aortic aneurysm among patients of European ancestry. 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 ( < 5 × 10) 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. 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. There was a positive causal relationship between hypertension, BMI, WHR, and WHRadjBMI and aortic aneurysm.

摘要

为研究欧洲血统患者中高血压、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系。我们进行了两样本孟德尔随机化(MR)分析,以研究12种可改变的危险因素与主动脉瘤之间的因果关系,这些因素包括高血压、体重指数(BMI)、腰臀比(WHR)、糖尿病、吸烟、饮酒和咖啡摄入、身体活动以及睡眠时间。从欧洲血统全基因组关联研究中提取全基因组显著的危险因素遗传工具(<5×10),而主动脉瘤遗传工具则从英国生物银行和芬兰基因队列中选取。采用逆方差加权MR作为主要分析方法,并进行MR-Egger(MRE)、加权中位数MR、MR多效性残差和离群值分析以及Phenoscanner搜索作为敏感性分析。此外,我们计算MRE截距以检测多效性,并进行Cochran's Q统计以评估异质性,还进行了双向MR和MR Steiger检验以排除反向因果关系的可能性。我们观察到高血压[合并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)]、调整BMI后的WHR(WHRadjBMI)[OR:1.35(95%CI 1.12-1.63)]、开始吸烟年龄[OR:1.63(95%CI 1.18-2.26)]以及烟草使用(开始、戒烟和重度吸烟)[OR:2.88(95%CI 1.85-2.26)]患者发生主动脉瘤的风险显著更高。在敏感性分析中,高血压、BMI、WHRadjBMI以及烟草使用(开始、戒烟和重度吸烟)的因果效应仍然稳健。高血压、BMI、WHR和WHRadjBMI与主动脉瘤之间存在正向因果关系。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7cd9/9393757/6636b2cca6d2/fgene-13-925874-g001.jpg

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