Association between hemoglobin glycation index and 5-year major adverse cardiovascular events: the REACTION cohort study

BACKGROUND: The hemoglobin glycation index (HGI) was developed to quantify glucose metabolism and individual differences and proved to be a robust measure of individual glycosylated hemoglobin (HbA1c) bias. Here, we aimed to explore the relationship between different HGIs and the risk of 5-year major adverse cardiovascular events (MACEs) by performing a large multicenter cohort study in China. METHODS: A total of 9791 subjects from the Risk Evaluation of Cancers in Chinese Diabetic Individuals: a Longitudinal Study (the REACTION study) were divided into five subgroups (Q1–Q5) with the HGI quantiles (≤5th, >5th and ≤33.3th, >33.3th and ≤66.7th, >66.7th and ≤95th, and >95th percentile). A multivariate logistic regression model constructed by the restricted cubic spline method was used to evaluate the relationship between the HGI and the 5-year MACE risk. Subgroup analysis between the HGI and covariates were explored to detect differences among the five subgroups. RESULTS: The total 5-year MACE rate in the nationwide cohort was 6.87% (673/9791). Restricted cubic spline analysis suggested a U-shaped correlation between the HGI values and MACE risk after adjustment for cardiovascular risk factors (χ(2) = 29.5, P <0.001). After adjustment for potential confounders, subjects with HGIs ≤–0.75 or >0.82 showed odds ratios (ORs) for MACE of 1.471 (95% confidence interval [CI], 1.027–2.069) and 2.222 (95% CI, 1.641–3.026) compared to subjects with HGIs of >–0.75 and ≤–0.20. In the subgroup with non-coronary heart disease, the risk of MACE was significantly higher in subjects with HGIs ≤–0.75 (OR, 1.540 [1.039–2.234]; P = 0.027) and >0.82 (OR, 2.022 [1.392–2.890]; P <0.001) compared to those with HGIs of ≤–0.75 or >0.82 after adjustment for potential confounders. CONCLUSIONS: We found a U-shaped correlation between the HGI values and the risk of 5-year MACE. Both low and high HGIs were associated with an increased risk of MACE. Therefore, the HGI may predict the 5-year MACE risk.