Abstract Background and aims Atherothrombotic and small-vessel ischemic stroke are physiopathologically distinct, yet differences in their systemic metabolic and inflammatory signatures remain poorly defined. This exploratory study examined whether metabolomic and inflammatory markers differ between these two etiologies. Methods We conducted a cross-sectional analysis including patients with atherothrombotic stroke (n=22) or small-vessel stroke (n=10). Metabolomic variables (amino acids, energy-related metabolites, lipid subclasses) and inflammatory markers (blood cell counts, NLR, CRP, Glyc-A/B/F) were evaluated at admission. Separate linear regression models were fitted for each variable, adjusting for age, sex, diabetes mellitus type 2 and dyslipidaemia; the atherothrombotic subtype served as reference. Statistical significance was defined as p 0.05. Results Three metabolites showed significantly higher levels in the small-vessel group: glutamate (β = +50.7, p = 0.0096), lactate (β = +443.9, p = 0.0320), and threonine (β = +30.3, p = 0.0449). No inflammatory biomarker demonstrated significant differences. The concurrent increase in glutamate, lactate and threonine may reflect a coordinated metabolic shift involving glycolytic acceleration, mitochondrial strain and enhanced amino-acid turnover, although causality cannot be inferred in this exploratory context. Interpretation is constrained by the small sample size, cross-sectional design, limited covariate adjustment and the absence of longitudinal metabolic profiling. This analysis identifies a potential metabolic signature distinguishing small-vessel from atherothrombotic stroke, while inflammatory markers showed no discriminatory value. Larger, longitudinal studies are required to validate these preliminary findings. Conflict of interest No conflicts of interest for any author Figure 1 - belongs to Results
Sáez et al. (Fri,) studied this question.