Abstract 4142841: Relationship Between Amino Acid Metabolomics in Patients with Acute Ischemic Stroke Undergoing Intervention

Background: Emerging data reveal the importance of metabolomics in identifying specific amino acids and their metabolites as markers of hypercoagulability and stroke. Hypercoagulability, measured by a global hemostasis assay, is associated with thrombotic risk in patients with acute ischemic stroke (AIS). Hypothesis: AIS Patients undergoing coronary intervention compared to healthy controls (HC) exhibit dysregulated amino acid metabolomics that is associated with coagulation. Methods: Serum samples were collected from HC and AIS patients during the intervention. Untargeted metabolomics was performed using a Thermo-Scientific Q Exactive Plus Orbitrap mass spectrometer with Vanquish Horizon Binary UPLC. Metabolomics results were normalized relative to control subjects and compared to patients with AIS. Whole blood samples were used for the TEG assay, and the results were compared between patients with AIS and HC. Hypercoagulability was defined as platelet-fibrin clot strength (P-FCS) > 66.5 mm. Results: AIS patients undergoing interventional procedures (n=12) and HC (n=17) were included. Among AIS patients, 50% were black, 67% were male, and 67% were obese. AIS patients vs. controls had elevated levels of P-FCS (67±3mm vs. 62±2mm) and a higher prevalence of hypercoagulability (83% vs. 0%) (p<0.05 for both). Compared to HC, patients with AIS had negative correlation with histidine (his), glutamine (Glu), arginine, lysine (Lys), asparagine (ASP), homoarginine (Harg), ornithine (orn), valine (Val), homocysteine (Hcyc), anthranilate (Ant), serotonin (Ser), tryptophan (Trp), proline (Prl), alanine (Ala), and beta-alanine (Bala). They positively correlated with kynurenine (Kyn), xanthine (Xan), and xanthosine (Xanth) (P<0.05 for all, Figur ). Conclusions: This hypothesis-generating study of untargeted metabolomics revealed that patients with AIS at the time of intervention were characterized by significant hypercoagulability and dysregulation of amino acids associated with coagulation. Further studies are planned to analyze the relationship between these amino acids and AIS risk and to identify them as novel prognostic risk factors.