In this study, we analyzed plasma samples from 484 ischemic stroke patients, comprising 392 individuals without AF and 92 with AF, to identify metabolic alterations associated with AF-related stroke. We employed semi-targeted metabolomic analysis using ultrahigh-performance liquid chromatography coupled with a triple quadrupole mass spectrometer (UPLC-TQ-MS; Agilent 1290 Infinity LC and 6495 TQ-MS system). The metabolomic profiling revealed notable differences in various polar metabolites—including amino acids, purine derivatives, and acylcarnitines—between the two groups. Remarkably, medium-chain acylcarnitines (hexanoylcarnitine, octanoylcarnitine, decanoylcarnitine, and lauroylcarnitine) were significantly elevated in patients with AF. After semi-targeted profiling, we conducted targeted analysis for 4 aclycarnitines using same instruments. Quantitatively, medium-chain acylcarnitines increased significantly compared to non-AF stroke patients. This trend was also shown in the validation set, with statistical significance determined by the Mann-Whitney U test. 

These findings indicate a potential link between specific circulating metabolites and the presence of AF in ischemic stroke, suggesting their relevance in improving stroke subtype differentiation and enhancing our understanding of its underlying pathophysiology.