Nonlinear association of the hemoglobin glycation index with all-cause and cardiovascular mortality: A...

The hemoglobin glycation index (HGI) has been increasingly recognized for predicting cardiovascular outcomes. However, its association with all-cause and cardiovascular disease (CVD) mortality in the general population remains underexplored. This study aimed to investigate the nonlinear relationship between the HGI and mortality, identify risk thresholds, and evaluate HGI's clinical utility for individualized risk stratification.

4857 participants from the Fangshan Family-based Ischemic Stroke Study in China (FISSIC) were included. Death dates were obtained by reviewing the death certificates until 2024/7/31. During a median follow-up of 8 years, 652 deaths were identified, including 379 deaths due to CVD. HGI was calculated as HGI = Observed hemoglobin A1c (HbA1c) - Predicted HbA1c. Cox proportional hazard regression models and restricted cubic splines were constructed to assess the relationship of HGI with mortality risk.

This study revealed a J-shaped association of HGI with both all-cause and CVD mortality. For all-cause mortality, when HGI was below the threshold point (-0.58), the mortality risk slightly decreased with increasing HGI, with a hazard ratio (HR) of 0.821 (95 %CI: 0.666-1.011, P = 0.064). Conversely, when HGI exceeded -0.58, the mortality risk significantly increased with higher HGI (HR: 1.193, 95 % CI: 1.104-1.289, P < 0.001). CVD mortality exhibited similar threshold effects, with HGI < -0.58 trended toward lower risk (HR: 0.80, 95 %CI: 0.60-1.06, P = 0.114), whereas HGI > -0.58 showed marked risk elevation (HR: 1.23, 95 %CI: 1.11-1.36, P < 0.001).

This study demonstrates a nonlinear relationship of HGI with both all-cause and CVD mortality.