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<p>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 B<sub>2</sub> 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 B<sub>2</sub>, 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&#xa0;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 B<sub>2</sub>, 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; <i>p</i> = 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); <i>p</i> = 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.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年10月8日

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  • Nils-Ole Gloyer,
  • Eileen Moritz,
  • Laura Schwieren,
  • Ulrike Meyer,
  • Götz Thomalla,
  • Günter Daum,
  • Tim Magnus,
  • Rainer Böger,
  • Chi-un Choe,
  • Bernhard H. Rauch,
  • Edzard Schwedhelm

摘要

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.