Prospective study of hemoglobin A1c and incident carotid artery plaque in Chinese adults without diabetes

Background: Diabetes has been reported to be associated with carotid artery plaque (CAP). However, it remains unclear whether hemoglobin A1c (HbA1c) level, a marker for long-term glycemic status, is associated with altered CAP risk in individuals with fasting blood glucose (FBG) concentrations below the current cutoff for diabetes. Methods: Included were 16,863 Chinese adults (aged 18 years or more; 9855 men and 7008 women) with fasting blood glucose < 7.0 mmol/L at baseline (2013). Both HbA1c level and CAP (assessed via ultrasound B-mode imaging) were annually assessed during 2014-2018. All the participants were further classified into three groups based on baseline HbA1c level: ≤ 5.6%, 5.7-6.4%, and ≥ 6.5%. We used Cox proportional-hazards model to evaluate the association between HbA1c level and incident CAP, adjusting for a series of potential confounders. Results: During 5 years of follow up, 3942 incident CAP cases were identified. Individuals with higher baseline HbA1c had higher future risk of CAP (p-trend < 0.001). In the full-adjusted model, each percent increase of HbA1c was associated with a 56% (HR = 1.56, 95% CI 1.37, 1.78) higher risk of CAP. Excluding participants with chronic inflammation, as assessed by high-sensitivity C-reactive protein and white blood cell, and those with FBG ≥ 5.6 mmol/L at baseline generated similar results. Conclusions: Elevated HbA1c level was associated with high risk of developing CAP in Chinese adults without FBG defined diabetes.