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Background <p>Cardiovascular-kidney-metabolic (CKM) syndrome is a recently proposed multisystem disorder with high prevalence and progressive stages from 0 to 4, characterized by uncertain risk factors. Hemoglobin glycation index (HGI), a simple marker reflecting individual variation in glycated hemoglobin, has been linked to diabetic and cardiovascular outcomes. However, its association with CKM syndrome severity and mortality remains unknown.</p> Methods <p>This study utilized data from the National Health and Nutrition Examination Survey (1999–2018) and included 14,680 adult participants. Weighted logistic regression was conducted to assess the association of HGI and CKM syndrome stage. Kaplan-Meier survival curves and weighted Cox proportional hazards models were adopted to explore the relationship between HGI and mortality by CKM syndrome stages, followed with analyses of restricted cubic spline and threshold effect.</p> Results <p>A positive correlation between HGI and CKM syndrome stage was observed after multivariate adjustment (OR 1.24, 95% CI 1.10–1.39). Over a median follow-up period of 7.5 years, a total of 1,111 all-cause deaths and 349 cardiovascular deaths were documented. U-shaped associations between HGI and all-cause mortality were observed, with inflection points at -0.280 (CKM syndrome stage 0–3) and − 0.077 (CKM syndrome stage 4). A one-unit increase in HGI was linked to a 33–39% reduction in all-cause mortality risk below the inflection point, and a 33–42% increase above it. In contrast, HGI showed a linear association with cardiovascular mortality in participants with CKM syndrome stage 4 (HR 1.34, 95% CI 1.08–1.65), however, no significant association was observed in CKM syndrome stage 0–3.</p> Conclusions <p>A higher HGI was associated with increased severity of CKM syndrome. There was a U-shaped relationship between HGI and all-cause mortality while a linear association between HGI and cardiovascular mortality was observed depending on the CKM syndrome stage. HGI may serve as a valuable biomarker for assessing the risk of CKM syndrome and its related mortality.</p>

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Association of hemoglobin glycation index with the severity and mortality of cardiovascular-kidney-metabolic syndrome: a population-based cohort study

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年12月20日

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  • Leiluo Geng,
  • Xue Diao,
  • Hong-jie Yu,
  • Aimin Xu

摘要

Background

Cardiovascular-kidney-metabolic (CKM) syndrome is a recently proposed multisystem disorder with high prevalence and progressive stages from 0 to 4, characterized by uncertain risk factors. Hemoglobin glycation index (HGI), a simple marker reflecting individual variation in glycated hemoglobin, has been linked to diabetic and cardiovascular outcomes. However, its association with CKM syndrome severity and mortality remains unknown.

Methods

This study utilized data from the National Health and Nutrition Examination Survey (1999–2018) and included 14,680 adult participants. Weighted logistic regression was conducted to assess the association of HGI and CKM syndrome stage. Kaplan-Meier survival curves and weighted Cox proportional hazards models were adopted to explore the relationship between HGI and mortality by CKM syndrome stages, followed with analyses of restricted cubic spline and threshold effect.

Results

A positive correlation between HGI and CKM syndrome stage was observed after multivariate adjustment (OR 1.24, 95% CI 1.10–1.39). Over a median follow-up period of 7.5 years, a total of 1,111 all-cause deaths and 349 cardiovascular deaths were documented. U-shaped associations between HGI and all-cause mortality were observed, with inflection points at -0.280 (CKM syndrome stage 0–3) and − 0.077 (CKM syndrome stage 4). A one-unit increase in HGI was linked to a 33–39% reduction in all-cause mortality risk below the inflection point, and a 33–42% increase above it. In contrast, HGI showed a linear association with cardiovascular mortality in participants with CKM syndrome stage 4 (HR 1.34, 95% CI 1.08–1.65), however, no significant association was observed in CKM syndrome stage 0–3.

Conclusions

A higher HGI was associated with increased severity of CKM syndrome. There was a U-shaped relationship between HGI and all-cause mortality while a linear association between HGI and cardiovascular mortality was observed depending on the CKM syndrome stage. HGI may serve as a valuable biomarker for assessing the risk of CKM syndrome and its related mortality.