Abstract
BACKGROUND: The hemoglobin glycation index (HGI) presents a discrepancy between observed and predicted glycosylated hemoglobin (HbA1c) and fasting blood glucose values. Meanwhile, compared to the HbA1c values, the HGI provides a more comprehensive reflection of blood glucose variability across populations. However, no studies have examined the association between the HGI and all-cause, cardiac, and cardiovascular mortalities in the general population. Hence, this study aimed to investigate these relationships using data from the National Health and Nutrition Examination Survey (NHANES) database. METHODS: Participants were stratified into four groups based on the HGI quartiles. Weighted multivariable Cox proportional hazards models were used to assess the associations between HGI and all-cause, cardiovascular, and cardiac mortality. Kaplan-Meier survival analysis based on the HGI quartiles and log-rank tests were employed to compare differences in primary and secondary endpoints. Additionally, restricted cubic spline (RCS) curves were used to explore nonlinear relationships between the HGI and endpoints, identifying inflection points. Subgroup analyses and interaction tests were conducted to assess the robustness of the findings. RESULTS: In comparing the baseline characteristics of endpoints across all-cause mortality, cardiac mortality, and cardiovascular mortality, significantly higher mortality rates were observed in the high HGI quartile group (Q4) compared to the other three groups (Q1, Q2, and Q3) (p < 0.05). Kaplan-Meier curves demonstrated increased mortality risks in the high HGI group across all endpoints (p < 0.05). Multivariable Cox proportional hazards models indicated that high HGI levels were associated with all-cause mortality (Q4: hazard ratio (HR) (95% confidence interval (CI)) = 1.232 (1.065, 1.426); p = 0.005), cardiac mortality (HR (95% CI) = 1.516 (1.100, 2.088); p = 0.011) and cardiovascular mortality (HR (95% CI) = 1.334 (1.013, 1.756); p = 0.039). Low HGI was associated only with all-cause mortality (Q1: HR (95% CI) = 1.269 (1.082, 1.488); p = 0.003). RCS analysis confirmed a U-shaped relationship between the HGI and all three outcome events. Subgroup analyses and interaction tests supported the robustness of the conclusions. CONCLUSION: This study demonstrates a U-shaped association between the HGI and overall mortality, cardiac mortality, and cardiometabolic mortality in the general population. Specifically, the high HGI value represented a risk factor for all-cause, cardiac, and cardiovascular mortality. In contrast, low HGI values were associated only with all-cause mortality in the general population.