Potential blood biomarkers to differentiate ischemic and hemorrhagic strokes

Background Currently, besides neuroimaging, there is a lack of alternative methods for rapid differentiation of ischemic stroke (IS) and intracerebral hemorrhage (ICH), which significantly impacts the timely treatment of patients. This study aims to elucidate the causal relationship between circulating metabolites and susceptibility to IS and ICH. Methods A two-sample Mendelian Randomization (MR) analysis was performed to estimate the causality of metabolites and metabolite ratios on IS/ICH. For exposure data, we extracted genetic variants associated with 1, 091 plasma metabolites and 309 metabolite ratios traits from the Canadian Longitudinal Study on Aging (CLSA) cohort (n = 8, 299). For outcomes, we selected IS and its three subtypes including cardioembolic stroke (CES), small vessel stroke (SVS), and large artery (LAS) from the latest stroke genome-wide association studies (GWAS) database (73, 652 patients). In addition, we have included ICH as a primary outcome (n = 1, 545 cases). Results In this MR analysis, there were 115, 105, 89, 70, and 48 plasma metabolites or metabolite ratios suggestive associated with IS, LAS, CES, SVS, and ICH. After false discovery rate (FDR) correction and sensitive analysis, 20 robust causative associations between 16 metabolites (e.g., ribitol, campesterol, and thymol sulfate)/ 4 metabolite ratios and IS or ICH were finally identified. Among them, six metabolites may serve as potential indicators for distinguishing between IS and ICH. Conclusion The finding of our study suggested that identified metabolites and metabolite ratios can be considered useful circulating biomarkers for IS and ICH screening and differential diagnosis in clinical practice.