CONTEXT There is a substantial interindividual variation in the association between glycated hemoglobin (HbA1c) and plasma glucose concentrations. Its impact on cardiovascular disease (CVD) has not been comprehensively evaluated.

OBJECTIVE We examined associations between interindividual variations in HbA1c, which was estimated as the hemoglobin glycation index (HGI), and CVD.

DESIGN, SETTING, AND PARTICIPANTS We performed a cross-sectional analysis with 1248 treatment-naïve subjects with prediabetes or diabetes. The HGI was defined as the measured HbA1c minus predicted HbA1c, which was calculated from the linear relationship between HbA1c and fasting plasma glucose levels.

MAIN OUTCOME MEASURES The prevalence of composite and individual CVDs including coronary artery disease (CAD), stroke, and peripheral artery disease (PAD).

RESULTS The overall prevalence of composite CVD was 10.3% and individual prevalences of CAD, stroke, and PAD were 5.7%, 5.1%, and 1.3%, respectively. All prevalences significantly increased from the first to third tertile of HGI. In multivariate analysis, the highest HGI tertile was independently associated with composite CVD [odds ratio (95% confidence interval): 2.81 (1.59-4.98)], and individual CAD [2.30 (1.12-4.73)], stroke [3.40 (1.50-7.73)], and PAD [6.37 (1.18-34.33)] after adjustment for other CVD risk factors including HbA1c levels. Two consecutive measurements of HGI obtained on different days showed good correlation (r = 0.651, P < 0.001) and high concordance rate in the tertile classification (69.1%).

CONCLUSIONS High HGI was independently associated with overall and individual CVDs. This result suggests that discrepancy between HbA1c and fasting glucose levels can reflect vascular health in subjects with impaired glucose metabolism.