Association of lifestyle factors and genetic risk with incident abdominal aortic aneurysm.

Abstract

Although lifestyle factors are associated with the risk of abdominal aortic aneurysm (AAA), its relationship with genetic susceptibility in determining AAA remains unclear. We aim to investigate the association of lifestyle factors and genetic risk with the incidence of AAAs. A prospective cohort study, including 274,755 adult participants with White European ancestry and no AAA at baseline, was recruited between 2006 and 2010. A polygenic risk score was calculated to quantify genetic susceptibility to AAA in participants, and a comprehensive healthy lifestyle score was derived based on factors including sleep, diet, alcohol consumption, physical activity, waist-to-hip ratio, and smoking. Incident AAAs were determined by linking medical history with hospital admission and death registries. Participants at high genetic risk had an 89% higher risk of AAAs compared with those at low genetic risk. A poor lifestyle was associated with a 165% increased risk of developing AAAs compared with a healthy lifestyle. Participants with both a poor lifestyle and high genetic risk exhibited the highest risk, with a hazard ratio for incident AAAs of 4.64 (95% confidence interval, 2.59-8.31) compared with those at low genetic risk and a healthy lifestyle. Moreover, there was a significant positive additive interaction between poor lifestyle and high genetic risk (relative excess risk due to interaction: 1.81; 95% confidence interval, 0.69-2.92). High genetic risk and poor lifestyle were both independently and jointly associated with an increased risk of AAAs. Moreover, following a healthy lifestyle can reduce the risk of AAAs for individuals, particularly among those with high genetic risk.