# Associations of biological ageing and genetic risk with incident abdominal aortic aneurysm

## TL;DR

This study finds that accelerated biological aging increases the risk of developing abdominal aortic aneurysms, especially in those with high genetic risk.

## Contribution

The study establishes biological aging as a significant risk factor for AAA when combined with genetic predisposition.

## Key findings

- Accelerated biological aging is linked to a higher risk of AAA, with hazard ratios of 1.29 (KDMAge) and 1.63 (PhenoAge).
- Individuals with both accelerated biological aging and high genetic risk have the highest AAA risk (HRs of 2.15 and 2.72).
- There is a significant additive interaction between genetic risk and PhenoAge-based accelerated aging.

## Abstract

Abdominal aortic aneurysm (AAA) is a degenerative cardiovascular disorder prevalent with ageing. While accelerated biological ageing contributes to age-related diseases, its specific role in AAA risk remains unclear. This study investigates the relationships between biological ageing and risk of incident AAA and genetic predisposition to the disease.

This retrospective study used UK Biobank data from 350,483 participants without AAA at baseline. Biological age was assessed using Klemera-Doubal Method (KDMAge) and phenotypic age (PhenoAge) algorithms. Accelerated biological ageing was determined through residual analysis against chronological age, with values above 0 indicating accelerated ageing. Cox proportional hazards models evaluated the associations of biological age accelerations with AAA risk. Polygenic risk scores were calculated to evaluate genetic predisposition to AAA. We also examined the interactions between biological age accelerations and genetic predisposition on the risk of AAA.

Here we show that participants with accelerated biological ageing have an elevated risk of AAA onset compared to those without, with hazard ratios (HRs) of 1.29 (95% CI 1.17-1.42) for KDMAge and 1.63 (95% CI 1.47-1.81) for PhenoAge. For joint associations, participants with accelerated biological ageing and high genetic risk have the highest risk of incident AAA (KDMAge: HR 2.15, 95% CI 1.81-2.54; PhenoAge: HR 2.72, 95% CI 2.26-3.28). There is a significant additive interaction between high genetic risk and accelerated biological ageing of PhenoAge.

Accelerated biological ageing is significantly associated with an increased risk of AAA incidence, suggesting its potential as a focal point for risk assessment and targeted intervention development.

Abdominal aortic aneurysm (AAA) is a life-threatening cardiovascular degenerative disease, for which ageing is a non-negligible risk factor. However, the specific role of accelerated biological ageing remains unclear. We investigated this relationship in over 350,000 participants in the UK, measuring biological age using clinical biomarker-based algorithms and assessing its association with future AAA risk, alongside genetic predisposition. We found that accelerated biological ageing significantly increased the risk of developing AAA, with the highest risk observed in individuals who also had high genetic risk. These findings establish biological ageing as a significant risk factor for AAA. Assessing biological age, especially in combination with genetic risk, could help identify at-risk individuals early and guide targeted prevention strategies.

Yao, You, Shen et al. evaluate the association between accelerated biological ageing and risk of incident abdominal aortic aneurysm (AAA) in the UK Biobank. They find that accelerated biological ageing significantly elevates AAA risk, with the highest risk observed in individuals with underlying genetic predisposition.