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

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.