Association between glycated hemoglobin A1c and automated abdominal aortic calcification: the UK Biobank Imaging Study

Background: Poor glycemic control is associated with cardiovascular disease (CVD) risk. However, it is unknown whether glycemic control is related to abdominal aortic calcification (AAC), a marker of subclinical CVD. We investigated the association between glycated hemoglobin (HbA1c) and moderate-to-high automated AAC among middle-aged to older adults from the general population. Methods:We included UK Biobank Imaging Study participants free of atherosclerotic CVD at baseline. HbA1c was measured at baseline (2006-2010) and categorized as normoglycemia (<39.0 mmol/mol), prediabetes (39.0-47.9 mmol/mol), undiagnosed diabetes (HbA1c [&ge;]48 mmol/mol), and diagnosed diabetes. Machine learning-derived AAC24 (ML-AAC24) scores were estimated using a validated automated algorithm applied to dual-energy X-ray absorptiometry lateral spine images (2014-2022). The associations of HbA1c with moderate-to-high ML-AAC24 (defined as a score [&ge;]2) were assessed using logistic regression adjusting for cardiovascular risk factors. Results: Of the included 48,912 participants (mean {+/-} SD age 55 {+/-} 7.6 years, 52% women), 9.7% had prediabetes (HbA1c 39.0-47.9 mmol/mol [5.7-6.4%]), 0.4% had undiagnosed diabetes, and 2.7% had diagnosed diabetes. Each 1-SD increase in log-transformed HbA1c was associated with higher odds of moderate-to-high ML-AAC24 (adjusted odds ratio [aOR] 1.12, 95% CI: 1.09-1.16). Amongst individuals with normal HbA1c, this association was consistent but somewhat weaker for each 1-SD increase in log-transformed HbA1c (aOR 1.07, 95% CI 1.03-1.10). Compared to participants with normal HbA1c, those with prediabetes (aOR 1.19, 95% CI: 1.08-1.30) or diagnosed diabetes (1.64, 95% CI: 1.39-1.94) had higher odds of moderate-to-high ML-AAC24. These associations were consistent in stratified analyses by sex, age groups, body mass index, smoking status and total cholesterol Conclusions: Linear associations between HbA1c levels and ML-AAC24 were observed in UK adults, even in those with normal HbA1c levels. These findings indicate that AAC may develop early in the dysglycemic continuum, supporting earlier cardiometabolic risk assessment even amongst people with ?normal? levels.