Lipoprotein disruption following ischemic stroke across subtypes and over time: Findings from NMR-based metabolomic...

Despite rising stroke rates, we still lack reliable blood biomarkers to elucidate mechanisms, refine subtypes, and track recovery. We investigated whether high-throughput nuclear magnetic resonance (NMR) spectroscopy, including lipid-ratio metrics, could uncover pathway disruptions across stroke subtypes and over six months. Between October 2018 and July 2019, we recruited acute ischemic stroke patients and age-matched healthy controls. We quantified metabolites and ratio-based measures using NMR. Univariate tests and multivariable logistic regression (adjusting for relevant covariates) were employed to (1) compare ischemic stroke versus controls, (2) delineate subtype-specific differences, and (3) evaluate longitudinal biomarker changes. Overall, 523 stroke patients (mean age 57.4 years) and 203 controls were enrolled; 72 stroke patients provided follow-up samples at 6 months. Compared with controls, stroke patients showed elevated cholesteryl esters in intermediate-density lipoproteins (IDL), triglycerides in large and medium high-density lipoprotein (HDL), and cholesterol in IDL (all p < 0.05), alongside lower acetone, acetoacetate, and HDL-related measures. Stroke subtype analyses revealed particularly atherogenic lipid profiles in large artery disease (increased IDL cholesteryl esters, large HDL triglycerides); pronounced pyruvate and very small very-low-density lipoprotein (VLDL) disruptions in cardioembolism; and marked IDL/HDL abnormalities in lacunar stroke. Over six months, stroke survivors exhibited significant metabolic shifts, with increased glycine and the triglycerides-to-total-lipids ratios in medium, large, and small LDL six months following an ischemic stroke. However, these biomarker elevations did not correlate with functional recovery. NMR revealed stroke-specific lipid/ketone signatures, mapped stroke subtypes, and tracked recovery remodeling, yielding actionable prognostic biomarkers.