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

Abstract

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.

No causal association between inguinal hernia and aortic aneurysm using Mendelian randomization analysis

“…These findings suggest that there may be risk factors impacting both hernia and aortic aneurysm through common pathways. Observational and MR studies have confirmed smoking and abdominal obesity as prevalent factors [6]. Smoking can increase elastin degradation and aneurysm size, supporting previous observational studies that could elucidate relationships through confounders such as smoking [29,30].…”

“…Although TAA has different pathophysiological changes, AAA and TAA both share common risk factors such as smoking, age over 65, male sex, and family history [1,5,6]. Diseases like pulmonary emphysema and inguinal hernia have been found possible contributions to AAA [7].…”

The causal association between smoking initiation, alcohol and coffee consumption, and women’s reproductive health: A two-sample Mendelian randomization analysis

“…Finally, to avoid weak instrument bias, we calculated the F-statistics of each genetic instrument (SNP) ( Li and Martin, 2002 ; Palmer et al, 2012 ) and ensured strong effect sizes by selecting instruments with F-statistic values larger than 10 in our MR analysis. In conclusion, we finally selected 314 SNPs as smoking initiation IVs, 84 SNPs as alcohol drinking IVs, and 4 SNPs as coffee consumption IVs, and these instruments have been used in previous MR studies ( Georgiou et al, 2021 ; Yuan et al, 2021 ; Zhou et al, 2022 ). In addition, overview information of our selected instruments is listed in Table 1 , with additional details provided in Supplementary Table S1 .…”

The causal relationship between smoking and thoracic aortic aneurysm: Evidence from Mendelian randomization analysis

“…Existing MR research has confirmed a significant causal link between smoking and the development of aortic aneurysms. [9] Moreover, smoking has been implicated as a risk factor for AAAs. [10] However, the causal relationship between smoking and TAAs remains to be clarified.…”