Causal association between modifiable risk factors and aortic aneurysm and aortic dissection: A comprehensive Mendelian randomization study

Aortic aneurysms (AA) and aortic dissection (AD) are life-threatening cardiovascular conditions. While epidemiological studies have suggested associations with modifiable risk factors, their causal nature remains unclear. This study aimed to explore the causal links between modifiable risk factors and risks of AA and AD using Mendelian randomization. A 2-sample Mendelian randomization approach was applied, utilizing genetic instrumental variables from genome-wide association studies with a significance threshold of P < 5 × 108. Summary data for AA and AD were obtained from 209,836 participants. Causal effect estimates were calculated for the 46 risk factors using inverse-variance-weighted models. Vigorous physical activity reduced the risk of AA, whereas alcohol consumption and smoking increased it. Obesity traits, including high body mass index, waist circumference, and body fat mass, were associated with a higher AA risk. High-density lipoprotein cholesterol (HDL-C) had a protective effect against AA, whereas low-density lipoprotein cholesterol (LDL-C) and triglycerides increased the risk of AA. Hypertension and high diastolic blood pressure significantly elevated the risk of both AA and AD, whereas type 2 diabetes appeared to be protective against AA. A diet rich in oily fish was found to protect against AD. Liver enzymes and sex hormones were not significantly associated with AA risk. This study identified causal relationships between modifiable risk factors and AA/AD risk, emphasizing the importance of physical activity, obesity management, and dietary adjustments in preventing aortic diseases. These findings provide insights into public health and clinical practice.