Abstract / Summary
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.