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Introduction <p>Cardiovascular-kidney-metabolic (CKM) syndrome represents a complex interplay of metabolic dysfunction, cardiovascular disease, and chronic kidney disease, with stage 2 characterized by metabolic risk factors and subclinical organ damage. The albumin/globulin ratio (AGR), which integrates inflammatory and nutritional status, has shown prognostic value in chronic diseases; however, its role in stage 2 CKM syndrome remains unexplored.</p> Aim <p>To evaluate the prognostic value of AGR for all-cause, cardiovascular, and cancer mortality among adults with stage 2 CKM syndrome.</p> Methods <p>This nationwide cohort analysis included 13,148 adults with stage 2 CKM syndrome from NHANES (1999–2018). Participants were categorized by AGR levels (≤ 1.286, 1.286–1.500, &gt; 1.500). Mortality outcomes were ascertained through linkage to the National Death Index up to 2019. Cox proportional hazards models were used to assess the associations between AGR and mortality, adjusting for sociodemographic, lifestyle, and clinical factors.</p> Results <p>Higher AGR levels demonstrated significant inverse associations with mortality. Restricted cubic spline analysis revealed a significant inverse relationship for all-cause mortality (<i>P</i> for overall &lt; 0.01), characterized by a threshold effect whereby mortality risk increased significantly when AGR fell below approximately 1.4. Compared to the lowest AGR group, the highest group (&gt; 1.500) showed 35% lower all-cause mortality (HR = 0.65, 95% CI 0.52–0.80), 47% lower cardiovascular mortality (HR = 0.53, 95% CI 0.34–0.84), and 45% lower cancer mortality (HR = 0.55, 95% CI 0.36–0.84). Subgroup analysis showed that the predictive role of AGR was particularly evident in males, individuals &lt; 65 years, current smokers, and those who were non-overweight (BMI &lt; 25&#xa0;kg/m<sup>2</sup>).</p> Conclusion <p>AGR is a robust, independent predictor of all-cause, cardiovascular, and cancer mortality in adults with stage 2 CKM syndrome. The association with all-cause mortality exhibits a significant threshold effect, highlighting the importance of maintaining AGR above approximately 1.4. These findings support the use of AGR for early risk stratification and personalized management in this population.</p> Graphical Abstract <p></p>

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Prognostic Value of Albumin/Globulin Ratio for Mortality in Stage 2 Cardiovascular-Kidney-Metabolic Syndrome: A Nationwide Cohort Analysis (1999–2018)

  • 期刊论文

  • 发表日期：

    2026年3月27日

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  • Ciai Chen,
  • Shanni Ding,
  • Yao Wang,
  • Shuo Sun,
  • Jie Zhang,
  • Wanjuan Qiu,
  • Jiani Ruan,
  • Liqing Chen,
  • Hongying Pan

摘要

Introduction

Cardiovascular-kidney-metabolic (CKM) syndrome represents a complex interplay of metabolic dysfunction, cardiovascular disease, and chronic kidney disease, with stage 2 characterized by metabolic risk factors and subclinical organ damage. The albumin/globulin ratio (AGR), which integrates inflammatory and nutritional status, has shown prognostic value in chronic diseases; however, its role in stage 2 CKM syndrome remains unexplored.

Aim

To evaluate the prognostic value of AGR for all-cause, cardiovascular, and cancer mortality among adults with stage 2 CKM syndrome.

Methods

This nationwide cohort analysis included 13,148 adults with stage 2 CKM syndrome from NHANES (1999–2018). Participants were categorized by AGR levels (≤ 1.286, 1.286–1.500, > 1.500). Mortality outcomes were ascertained through linkage to the National Death Index up to 2019. Cox proportional hazards models were used to assess the associations between AGR and mortality, adjusting for sociodemographic, lifestyle, and clinical factors.

Results

Higher AGR levels demonstrated significant inverse associations with mortality. Restricted cubic spline analysis revealed a significant inverse relationship for all-cause mortality (P for overall < 0.01), characterized by a threshold effect whereby mortality risk increased significantly when AGR fell below approximately 1.4. Compared to the lowest AGR group, the highest group (> 1.500) showed 35% lower all-cause mortality (HR = 0.65, 95% CI 0.52–0.80), 47% lower cardiovascular mortality (HR = 0.53, 95% CI 0.34–0.84), and 45% lower cancer mortality (HR = 0.55, 95% CI 0.36–0.84). Subgroup analysis showed that the predictive role of AGR was particularly evident in males, individuals < 65 years, current smokers, and those who were non-overweight (BMI < 25 kg/m2).

Conclusion

AGR is a robust, independent predictor of all-cause, cardiovascular, and cancer mortality in adults with stage 2 CKM syndrome. The association with all-cause mortality exhibits a significant threshold effect, highlighting the importance of maintaining AGR above approximately 1.4. These findings support the use of AGR for early risk stratification and personalized management in this population.

Graphical Abstract