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Peer-reviewedCC BY 4.0Frontiers in Neurology

Predictive value of the homocysteine-to-albumin ratio for 90-day functional outcome in patients with spontaneous intracerebral hemorrhage

  1. 1Department of Neurosurgery, Donghai County Hospital of Traditional Chinese Medicine
  2. 2Department of Clinical Laboratory, Donghai County Hospital of Traditional Chinese Medicine

Abstract

Objective: This study aimed to evaluate the association between the homocysteine-to-albumin ratio (Hcy/Alb) and 90-day functional outcome in patients with spontaneous supratentorial intracerebral hemorrhage, and to assess its incremental prognostic value beyond established clinical and imaging predictors.

Methods: This single-center retrospective cohort study was conducted within a prognostic model updating framework and followed the TRIPOD reporting guideline. We consecutively included 356 patients with spontaneous supratentorial intracerebral hemorrhage admitted between January 2023 and December 2025. The primary outcome was unfavorable functional outcome at 90 days, defined as a modified Rankin Scale score of 4–6. A baseline model was developed using age, admission NIHSS score, hematoma volume, hemorrhage location, intraventricular hemorrhage, and midline shift ≥5 mm. Hcy/Alb was then added to construct a combined model. Multivariable logistic regression was used to assess the independent association between Hcy/Alb and outcome. Model performance and internal stability were evaluated using receiver operating characteristic curve analysis, calibration assessment, Brier score, decision curve analysis, bootstrap resampling, and 10-fold cross-validation.

Results: Among 356 patients, 218 (61.2%) had an unfavorable functional outcome at 90 days. In multivariable logistic regression, Hcy/Alb was independently associated with unfavorable outcome when analyzed as a continuous variable (OR = 1.25, 95% CI: 1.12–1.39, p < 0.001). Patients with Hcy/Alb above the median value of 0.42 also had a higher risk of unfavorable outcome than those with lower Hcy/Alb (OR = 2.65, 95% CI: 1.58–4.45, p < 0.001). Hcy/Alb alone showed moderate discrimination for unfavorable outcome, with an AUC of 0.78. The AUC increased from 0.82 in the baseline model to 0.86 in the combined model, and the difference was statistically significant by DeLong test ( p = 0.018). Internal validation showed a bootstrap-corrected AUC of 0.86 and a 10-fold cross-validation AUC of 0.85 for the combined model. Calibration indices, Brier score, and decision curve analysis indicated modest improvements in predictive agreement and relative net benefit after adding Hcy/Alb, although the absolute increase in discrimination was modest (ΔAUC = 0.04), indicating limited incremental predictive value beyond the established clinical and imaging predictors.

Conclusion: Hcy/Alb was independently associated with 90-day unfavorable functional outcome in patients with spontaneous supratentorial intracerebral hemorrhage. Adding Hcy/Alb to established clinical and imaging predictors provided statistically significant but limited incremental prognostic information (ΔAUC = 0.04). Therefore, Hcy/Alb should be interpreted as an adjunctive biomarker rather than a standalone prediction tool. Because this model was developed in a single-center retrospective cohort and evaluated only through internal validation, external validation in independent multicenter prospective cohorts is required before broader clinical application.

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BibTeX
@article{gao2026predictive,
  title = {{Predictive value of the homocysteine-to-albumin ratio for 90-day functional outcome in patients with spontaneous intracerebral hemorrhage}},
  author = {Qiang Gao and Xiaotong Chen and Jiaping Wang and Jian Zhou and Xiaoqing Diao},
  journal = {Frontiers in Neurology},
  year = {2026},
  month = nov,
  doi = {10.3389/fneur.2026.1928198},
  url = {https://www.frontiersin.org/articles/10.3389/fneur.2026.1928198/full},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Predictive value of the homocysteine-to-albumin ratio for 90-day functional outcome in patients with spontaneous intracerebral hemorrhage
AU  - Qiang Gao
AU  - Xiaotong Chen
AU  - Jiaping Wang
AU  - Jian Zhou
AU  - Xiaoqing Diao
PY  - 2026
DA  - 2026/11/03
JO  - Frontiers in Neurology
DO  - 10.3389/fneur.2026.1928198
UR  - https://www.frontiersin.org/articles/10.3389/fneur.2026.1928198/full
AB  - Objective: This study aimed to evaluate the association between the homocysteine-to-albumin ratio (Hcy/Alb) and 90-day functional outcome in patients with spontaneous supratentorial intracerebral hemorrhage, and to assess its incremental prognostic value beyond established clinical and imaging predictors.  Methods: This single-center retrospective cohort study was conducted within a prognostic model updating framework and followed the TRIPOD reporting guideline. We consecutively included 356 patients with spontaneous supratentorial intracerebral hemorrhage admitted between January 2023 and December 2025. The primary outcome was unfavorable functional outcome at 90 days, defined as a modified Rankin Scale score of 4–6. A baseline model was developed using age, admission NIHSS score, hematoma volume, hemorrhage location, intraventricular hemorrhage, and midline shift ≥5 mm. Hcy/Alb was then added to construct a combined model. Multivariable logistic regression was used to assess the independent association between Hcy/Alb and outcome. Model performance and internal stability were evaluated using receiver operating characteristic curve analysis, calibration assessment, Brier score, decision curve analysis, bootstrap resampling, and 10-fold cross-validation.  Results: Among 356 patients, 218 (61.2%) had an unfavorable functional outcome at 90 days. In multivariable logistic regression, Hcy/Alb was independently associated with unfavorable outcome when analyzed as a continuous variable (OR = 1.25, 95% CI: 1.12–1.39, p < 0.001). Patients with Hcy/Alb above the median value of 0.42 also had a higher risk of unfavorable outcome than those with lower Hcy/Alb (OR = 2.65, 95% CI: 1.58–4.45, p < 0.001). Hcy/Alb alone showed moderate discrimination for unfavorable outcome, with an AUC of 0.78. The AUC increased from 0.82 in the baseline model to 0.86 in the combined model, and the difference was statistically significant by DeLong test ( p = 0.018). Internal validation showed a bootstrap-corrected AUC of 0.86 and a 10-fold cross-validation AUC of 0.85 for the combined model. Calibration indices, Brier score, and decision curve analysis indicated modest improvements in predictive agreement and relative net benefit after adding Hcy/Alb, although the absolute increase in discrimination was modest (ΔAUC = 0.04), indicating limited incremental predictive value beyond the established clinical and imaging predictors.  Conclusion: Hcy/Alb was independently associated with 90-day unfavorable functional outcome in patients with spontaneous supratentorial intracerebral hemorrhage. Adding Hcy/Alb to established clinical and imaging predictors provided statistically significant but limited incremental prognostic information (ΔAUC = 0.04). Therefore, Hcy/Alb should be interpreted as an adjunctive biomarker rather than a standalone prediction tool. Because this model was developed in a single-center retrospective cohort and evaluated only through internal validation, external validation in independent multicenter prospective cohorts is required before broader clinical application.
SN  - 1664-2295
ER  -