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

## TL;DR

This study explores how sphingosine-1-phosphate and soluble P-selectin relate to adverse outcomes in patients with cerebral ischemia, with and without aspirin use.

## Contribution

The study is the first to investigate the associations of sphingosine-1-phosphate with soluble P-selectin and clinical outcomes in aspirin-treated and untreated ischemic stroke patients.

## Key findings

- High soluble P-selectin levels in aspirin-naive patients were linked to shorter event-free survival.
- Adjusted analysis showed a higher risk of adverse events in patients without aspirin and high soluble P-selectin.

## Abstract

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.

The online version contains supplementary material available at 10.1007/s00210-025-04595-w.