Glycated hemoglobin levels and abdominal aortic aneurysm incidence in primary prevention populations

Abdominal aortic aneurysm (AAA) is a life-threatening condition characterized by the pathological dilation of the abdominal aorta. Diabetes mellitus is a well-established risk factor for cardiovascular diseases, yet its relationship with AAA remains debated. We aimed to identify longitudinal associations between glycated hemoglobin A1c (HbA1c) level and the risk of AAA development.

A prospective cohort study was conducted using UK Biobank data, encompassing 326,152 participants aged 39 to 73 years, recruited from 2006 to 2010. Participants provided biological samples and completed questionnaires. AAA cases was identified via International Classification of Diseases, 10th edition, codes from linked health records. HbA1c levels and other covariates were measured. Logistic and Cox regression models were used to assess the associations between HbA1c levels and AAA prevalence and incidence. Restricted cubic spline models were applied to examine dose-response relationships. Subgroup, interaction, and sensitivity analyses were also performed.

The study revealed a nonlinear inverted U-shaped HbA1c-AAA risk relationship, with hazard ratios for AAA incidence peaking at 5.82% before declining. Compared with the lowest quartile of HbA1c levels, ascending quartiles showed progressively elevated AAA risks: Q2 = 1.14 (95% confidence interval [CI], 1.01-1.29), Q3 = 1.11 (95% CI, 0.98-1.26), Q4 = 1.27 (95% CI, 1.12-1.44; all P for trend < .05). Stratified analyses identified amplified risk escalation in younger age, elevated low-density lipoprotein cholesterol, and nondiabetic subgroups. Sensitivity analyses confirmed association robustness. Notably, younger participants (<65 years) exhibited 2.38-fold higher Q4/Q1 AAA risk (95% CI, 1.89-2.99).

This study reveals a bidirectional HbA1c-AAA incidence association, underscoring the clinical imperative for optimized glycemic control in primary AAA prevention, particularly among younger adults and hyperlipidemic patients.