Plasma Glutamine and Glutamate in Relation to Clinical Outcomes After Ischemic Stroke: A Multicenter Prospective Study
5 affiliations
- 1The Second Affiliated Hospital of Soochow University
- 2Suzhou Medical College of Soochow University
- 3University of Liverpool
- 4Affiliated Hospital of North China University of Science and Technology
- 5The First Affiliated Hospital of Soochow University
Abstract
Background Glutamine (Gln) and glutamate (Glu) have been suggested to play a pivotal role in neuronal homeostasis and metabolic regulation, showing potential as prognostic biomarkers for stroke. This study aimed to evaluate the associations of plasma Gln, Glu, and glutamine‐to‐glutamate ratio (GGR) with adverse clinical outcomes in patients with ischemic stroke. Methods This secondary analysis of the multicenter CATIS (China Antihypertensive Trial in Acute Ischemic Stroke) included 3499 participants with ischemic stroke. Plasma Gln and Glu levels were measured within 24 hours of hospital admission using ultraperformance liquid chromatography–tandem mass spectrometry. The primary outcome was unfavorable functional outcome (death or major disability) at 3 months after ischemic stroke. Secondary outcomes included major disability, all‐cause mortality, and cardiovascular events. Risk discrimination and reclassification of Glu metabolites were assessed. Results Compared with the lowest quartiles, multivariable‐adjusted odds ratios of the primary outcome in the highest quartiles were 0.37 (95% CI, 0.28–0.47) for Gln, 2.05 (95% CI, 1.60–2.62) for Glu, and 0.37 (95% CI, 0.29–0.48) for GGR (all P for trend <0.001). Approximately 9% of the associations of Glu metabolites and unfavorable functional outcome were mediated by the composite marker of inflammation and insulin resistance. Incorporating Gln, Glu, and GGR into conventional risk factor models improved risk discrimination and stratification for unfavorable functional outcome, with increases in C statistics (from 0.831 to 0.842–0.848), net reclassification indices (22.9%–31.0%), and integrated discrimination improvements (1.1%–1.6%) (all P <0.05). Conclusions Plasma Gln, Glu, and GGR were associated with adverse clinical outcomes, providing prognostic significance in patients with ischemic stroke. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01840072.
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BibTeX
@article{qin2026plasma,
title = {{Plasma Glutamine and Glutamate in Relation to Clinical Outcomes After Ischemic Stroke: A Multicenter Prospective Study}},
author = {Shengkai Qin and Ming Wang and Yanyu Zhu and Suyang Wu and Mingzhe Du and Yanbo Peng and Tan Xu and Yonghong Zhang and Xiang Xu and Chongke Zhong and Guodong Xiao},
journal = {Journal of the American Heart Association},
year = {2026},
month = oct,
doi = {10.1161/jaha.126.049903},
url = {https://www.ahajournals.org/doi/10.1161/JAHA.126.049903},
note = {CC BY-NC},
}
RIS
TY - JOUR
TI - Plasma Glutamine and Glutamate in Relation to Clinical Outcomes After Ischemic Stroke: A Multicenter Prospective Study
AU - Shengkai Qin
AU - Ming Wang
AU - Yanyu Zhu
AU - Suyang Wu
AU - Mingzhe Du
AU - Yanbo Peng
AU - Tan Xu
AU - Yonghong Zhang
AU - Xiang Xu
AU - Chongke Zhong
AU - Guodong Xiao
PY - 2026
DA - 2026/10/20
JO - Journal of the American Heart Association
DO - 10.1161/jaha.126.049903
UR - https://www.ahajournals.org/doi/10.1161/JAHA.126.049903
AB - Background Glutamine (Gln) and glutamate (Glu) have been suggested to play a pivotal role in neuronal homeostasis and metabolic regulation, showing potential as prognostic biomarkers for stroke. This study aimed to evaluate the associations of plasma Gln, Glu, and glutamine‐to‐glutamate ratio (GGR) with adverse clinical outcomes in patients with ischemic stroke. Methods This secondary analysis of the multicenter CATIS (China Antihypertensive Trial in Acute Ischemic Stroke) included 3499 participants with ischemic stroke. Plasma Gln and Glu levels were measured within 24 hours of hospital admission using ultraperformance liquid chromatography–tandem mass spectrometry. The primary outcome was unfavorable functional outcome (death or major disability) at 3 months after ischemic stroke. Secondary outcomes included major disability, all‐cause mortality, and cardiovascular events. Risk discrimination and reclassification of Glu metabolites were assessed. Results Compared with the lowest quartiles, multivariable‐adjusted odds ratios of the primary outcome in the highest quartiles were 0.37 (95% CI, 0.28–0.47) for Gln, 2.05 (95% CI, 1.60–2.62) for Glu, and 0.37 (95% CI, 0.29–0.48) for GGR (all P for trend <0.001). Approximately 9% of the associations of Glu metabolites and unfavorable functional outcome were mediated by the composite marker of inflammation and insulin resistance. Incorporating Gln, Glu, and GGR into conventional risk factor models improved risk discrimination and stratification for unfavorable functional outcome, with increases in C statistics (from 0.831 to 0.842–0.848), net reclassification indices (22.9%–31.0%), and integrated discrimination improvements (1.1%–1.6%) (all P <0.05). Conclusions Plasma Gln, Glu, and GGR were associated with adverse clinical outcomes, providing prognostic significance in patients with ischemic stroke. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01840072.
SN - 2047-9980
ER -