Glycated hemoglobin as a marker of subclinical atherosclerosis and cardiac remodeling among non-diabetic adults from the general population

Background: Elevated glycated hemoglobin (HbA1c) is associated with increased risk of cardiovascular disease (CVD) and mortality but little is known about potential mechanisms underlying the reported associations. Methods: We used data from 1798 non-diabetic participants from the population-based cohort Study of Health in Pomerania (SHIP) to investigate cross-sectional and longitudinal associations of HbA1c with subclinical atherosclerosis (common carotid artery intima-media thickness [CCA-IMT]), cardiac structure (left ventricular mass [LVM]), and cardiac function (fractional shortening). Results: Cross-sectional analyses revealed a positive association between HbA1c and mean CCA-IMT with a 0.02 mm (95% confidence interval: 0.01-0.04) increase in CCA-IMT per 1% increase in HbA1c, and a similar positive trend across HbA1c quartiles (overall p-value <0.01). We also observed a graded association between HbA1c and high CCA-IMT (>75th percentile) with an odds ratio of 1.42 (95% CI: 1.11-1.81) per 1% increase in HbA1c. Longitudinal analyses showed no consistent associations of baseline HbA1c with mean follow-up CCA-IMT. There were no consistent associations of HbA1c with cardiac remodeling in cross-sectional and longitudinal analyses, respectively. Conclusions: The association between HbA1c and CCA-IMT in non-diabetic adults may be a crucial link between high-normal HbA1c levels and an increased risk of CVD and mortality.