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. This cohort study included 86,184 males and 95,682 females aged ≥60years 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 visualize any nonlinear relationship. Harrell's C-index was calculated to assess the added value of HDL-C to the discrimination of model including age and smoking. Over a mean follow-up of 14.4years, 1549 and 328 incident AAA were observed in males and females, respectively. Adjusted hazard ratios for AAA with a 1-mmol/L HDL-C increase was 0.26 (95% confidence interval, 0.21- 0.32) and 0.31 (95% confidence interval, 0.21-0.46) in males and females, respectively (both P< .001). Consistent with the results from Cox model modelling HDL-C as a categorical variable showing an inverse and 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< .05). This study revealed a significant association between low HDL-C levels and a high risk of incident AAA in both older males and females, suggesting the potential clinical usefulness of HDL-C for AAA risk stratification. Our study was limited by its observational design and the 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.
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