Accelerated Biological Aging, Genetic Susceptibility, and the Risk of Abdominal Aortic Aneurysm: A Prospective Cohort Study.

Background: Biological age (BA) more accurately reflects the true ageing status of the body compared with chronological age. While biological aging is associated with various cardiovascular diseases, the relationship between BA and abdominal aortic aneurysms (AAAs) remains unclear. Methods: This study utilized data from the UK Biobank for analysis. Telomere length (TL) and BA acceleration, calculated using the Klemera-Doubal method (KDM) and phenotypic age (PhenoAge) methods, were used as surrogate measures of biological aging. Cox regression was primarily performed to explore the association between biological aging and AAA risk. Genetic susceptibility was assessed by constructing a polygenic risk score (PRS). Results: This study included 311,646 participants with a median age of 58 years. A total of 1339 new cases of AAA (4.33‰) were reported over a median follow-up period of 12.54 years. Each standard deviation (SD) increase in TL was associated with a 17% decreased risk of AAA (hazard ratio (HR) = 0.83, 95% confidence interval (CI) = 0.79-0.88). Each SD increase in BA acceleration in the KDM was associated with a 21% increased risk (HR = 1.21, 95% CI = 1.12-1.29), and and each SD increase in acceleration in the PhenoAge method was associated with a 40% increased risk (HR = 1.40, 95% CI = 1.32-1.48). These associations were independent of genetic risk, as assessed by the PRS, and a joint effect on AAA occurrence was observed. Additionally, we identified a sex-specific modification in the association between telomere shortening and AAA risk, with a significant association observed exclusively in men. Conclusions: Accelerated biological aging was longitudinally associated with an increased risk of AAA, suggesting that BA may be a significant factor and a potential biomarker for AAA.