Association between high-density-lipoprotein cholesterol and risk of abdominal aortic aneurysm among males and females aged 60 years and over

Objective: Whether high-density-lipoprotein cholesterol (HDL-c) has a protective role against abdominal aortic aneurysm (AAA) development in both older males and females remains uncertain. This study aims to assess the sex-specific association between HDL-c and incident AAA in older adults from the UK Biobank.

Methods: This cohort study included 86,184 males and 95,682 females aged ≥60 years from the UK biobank. Baseline HDL-c was modelled either as a continuous or categorical variable. The primary outcome was incident AAA. Cox proportional-hazard models were used for sex-stratified analysis, adjusting for baseline confounders. Restricted cubic splines were plotted to visualise any non-linear relationship. Harrell's C-index was calculated to assess the added value of HDL-c to the discrimination of model including age and smoking.

Results: Over a mean follow-up of 14.4 years, 1,549 and 328 incident AAA were observed in males and females, respectively. Adjusted HR (95%CI) for AAA with a 1 mmol/L HDL-c increase was 0.26 (0.21- 0.32) and 0.31 (0.21-0.46) in males and females, respectively, both p<0.001. Consistent with the results from Cox model modelling HDL-c as a categorical variable showing an inverse dose-dependent relationship between HDL-c and incident AAA in both sexes, restricted cubic splines confirmed the monotonic, inverse associations. Adding HDL-c to a model including age and smoking significantly improve the model discrimination for AAA in both sexes (C-index +2.1% in males and +1.5% in females, both p<0.05).

Conclusions: This study revealed a significant association between low HDL-c levels and high risk of incident AAA in both older males and females, suggesting the potential clinical utility of HDL-c for AAA risk stratification. Our study was limited by its observational design and presence of possible residual confounding. Studies using real-world data are warranted to evaluate the practical implications of incorporating HDL-c into AAA screening guidelines and its impact on patient outcomes.