Association of the hemoglobin glycation index with the large-artery atherosclerosis subtype in ischemic stroke: a dual-cohort study

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Association of the hemoglobin glycation index with the large-artery atherosclerosis subtype in ischemic stroke: a dual-cohort study

• 

  Xinyu Tong 1,2†

• J

  Jianxiong Gu 1†

• C

  Chuxin Lyu 3

• Y

  Yichun Zhao 1

• L

  Lei Chen 4

• T

  Tianzhi Ren 2

• H

  Haoxin Wu 2*

• L

  Lei Yu 1*

• Y

  Ying Rui 1*

• 1. Department of Neurology, Wuxi Affiliated Hospital of Nanjing University of Chinese Medicine, Wuxi, China

• 2. College of Traditional Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China

Abstract

Background: 

The hemoglobin glycation index (HGI) reflects discordance between measured HbA1c and glucose-predicted HbA1c, but in acute ischemic stroke (IS) it may also capture stress-hyperglycemia-related fasting plasma glucose (FPG) elevation. We examined the association of HGI with large-artery atherosclerosis (LAA) and in-hospital mortality.

Methods: 

We retrospectively analyzed 4,500 IS patients from MIMIC-IV and 330 patients from an external clinical cohort. HGI was calculated using cohort-specific FPG-HbA1c regression equations. Multivariable logistic regression and restricted cubic spline analyses assessed associations with LAA and mortality. Boruta feature selection, exploratory Mendelian randomization (MR), and post hoc stress hyperglycemia ratio (SHR) sensitivity analyses were also performed.

Results: 

Lower HGI was independently associated with higher LAA risk in both cohorts (MIMIC-IV: OR = 0.579, p < 0.001; clinical cohort: OR = 0.599, p < 0.001), with an L-shaped nonlinear pattern. In MIMIC-IV, lower HGI was also associated with higher in-hospital mortality (OR = 0.488, p < 0.001). HGI showed the highest Boruta feature importance among measured baseline variables. HGI and SHR were strongly inversely correlated in both cohorts (Spearman’s ρ = −0.711 and −0.723; both p < 0.001), and higher SHR showed directionally consistent associations with adverse outcomes. MR did not provide significant genetic evidence linking HGI to LAA.

Conclusion: 

Low HGI was associated with higher LAA risk and in-hospital mortality in IS. This signal overlaps with stress-hyperglycemia-related FPG-HbA1c discordance; therefore, HGI may be useful for risk stratification but should not be interpreted as an independent causal glycation phenotype.

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