Associations of sphingosine-1-phosphate with soluble P-selectin and adverse clinical outcome in patients with cerebral ischemia with and without acetylsalicylic acid treatment

Patients with overt cerebral ischemia are at risk for adverse events after hospital discharge. Sphingosine-1-phosphate is a potent lipid mediator produced and secreted by platelets, which is inhibited via acetylsalicylic acid (ASA). The associations of sphingosine-1-phosphate with biomarkers of platelet activation, i.e., thromboxane B₂ and soluble P-selectin, as well as with clinical outcome in ischemic stroke or transient ischemic attack patients' subgroups with and without ASA has not yet been investigated. The bioMARKers in STROKE (MARK-STROKE) cohort is a prospective, single-center, observational study including adult patients with a diagnosis of ischemic stroke or transient ischemic attack. Sphingosine-1-phosphate, thromboxane B₂, and soluble P-selectin were measured by liquid chromatography-tandem mass spectrometry and ELISA, respectively, to investigate cross-sectional and outcome associations in ASA medication groups. Overall, we included 374 patients (median age 70 (IQR 58; 78) years; sex 242 (64.7%) males; ASA, yes 270 (72.2%)). During the first 365 days of follow-up, we recorded 79 adverse events (death, stroke, myocardial infarction, rehospitalization) in 274 patients with available follow-up. While no statistical differences in neurological and functional deficits were determined by sphingosine-1-phosphate, thromboxane B₂, and soluble P-selectin in both ASA medication groups, patients without ASA intake and high soluble P-selectin had shorter event-free survival times (high soluble P-selectin 250 (95%CI 205; 296) days; low soluble P-selectin 331 (95%CI 304; 358) days; p = 0.005). In addition, adjusted Cox-regression analysis revealed a higher hazard ratio (HR) for an adverse event during follow-up (HR = 3.22 (95%CI 1.41; 7.36); p = 0.005). Our findings may indicate the usability of soluble P-selectin in ASA-naive patients with ischemic stroke/transient ischemic attack for risk stratification.