Circulating Microparticles in Patients with Symptomatic Carotid Disease Are Related to Embolic Plaque Activity and Recent Cerebral Ischaemia

Cerebrovasc Dis Extra. 2019;9(1):9-18. doi: 10.1159/000495942. Epub 2019 Apr 3.

Abstract

Background and purpose: In order to assess the association of microparticles derived from activated platelets (PMP) or endothelial cells (EMP) with risk markers for recurrent embolic events in patients with symptomatic carotid artery disease, we studied the associations between PMP/EMP and three risk markers: plaque haemorrhage (PH), micro-embolic signals and cerebral diffusion abnormalities.

Methods: Patients with recently symptomatic high-grade carotid artery stenosis (60-99%, 42 patients, 31 men; mean age 75 ± 8 years) and 30 healthy volunteers (HV, 11 men; mean age 56 ± 12 years) were prospectively recruited. Patients were characterised by carotid magnetic resonance imaging (presence of PH [MRI PH]), brain diffusion MRI (cerebral ischaemia [DWI+]) and transcranial Doppler ultrasound (micro-embolic signals [MES+]). PMP and EMP were classified by flow cytometry and expressed as log-transformed counts per microlitre.

Results: MES+ patients (n = 18) had elevated PMP (MES+ 9.61 ± 0.57) compared to HV (8.80 ± 0.73; p < 0.0001) and to MES- patients (8.55 ± 0.85; p < 0.0001). Stroke patients had elevated PMP (9.49 ± 0.64) and EMP (6.13 ± 1.0) compared to non-stroke patients (PMP 8.81 ± 0.73, p = 0.026, EMP 5.52 ± 0.65, p = 0.011) and HV (PMP 8.80 ± 0.73, p = 0.007, and EMP 5.44 ± 0.47, p = 0.006). DWI+ patients (n = 16) showed elevated PMP (DWI+ 9.53 ± 0.64; vs. HV, p = 0.002) and EMP (DWI+ 5.91 ± 0.99 vs. HV 5.44 ± 0.47; p = 0.037). Only PMP but not EMP were higher in DWI+ versus DWI- patients (8.67 ± 0.90; p = 0.002). No association was found between PMP and EMP with MRI PH.

Conclusions: PMP and EMP were associated with stroke and recent cerebrovascular events (DWI+) but only PMP were also associated with ongoing (MES+) thrombo-embolic activity suggesting a differential biomarker potential for EMP to index cerebral ischaemia while PMP may predict on-going thrombo-embolic activity.

Keywords: Amaurosis fugax; Brain diffusion magnetic resonance imaging; Cerebral ischaemia; Endothelial microparticles; Magnetic resonance imaging of carotid plaque haemorrhage; Micro-embolic signals; Platelet microparticles; Transcranial Doppler ultrasound.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Blood Platelets / pathology*
  • Brain Ischemia / blood
  • Brain Ischemia / diagnostic imaging
  • Brain Ischemia / etiology
  • Brain Ischemia / pathology*
  • Carotid Stenosis / blood
  • Carotid Stenosis / complications
  • Carotid Stenosis / diagnostic imaging
  • Carotid Stenosis / pathology*
  • Case-Control Studies
  • Cell-Derived Microparticles / pathology*
  • Diffusion Magnetic Resonance Imaging
  • Endothelial Cells / pathology*
  • Female
  • Flow Cytometry
  • Hemorrhage / pathology
  • Humans
  • Intracranial Embolism / blood
  • Intracranial Embolism / diagnostic imaging
  • Intracranial Embolism / etiology
  • Intracranial Embolism / pathology*
  • Male
  • Middle Aged
  • Plaque, Atherosclerotic*
  • Predictive Value of Tests
  • Prognosis
  • Prospective Studies
  • Risk Factors
  • Time Factors
  • Ultrasonography, Doppler, Transcranial
  • Young Adult