title: Circulating markers of endothelial dysfunction and platelet activation in patients with severe symptomatic cerebral small vessel disease.
abstract: BACKGROUND
  Small deep infarcts (SDI), also called lacunar infarcts, resulting from the occlusion of deep branch arteries, account for 25% of ischemic strokes. The physiopathology of the disease remains largely unknown. However, evidence about the role of endothelial dysfunction has emerged. Whereas chronic platelet activation is of major importance in acute thrombosis of large atherosclerotic arteries, its role in SDI remains unclear. Frequently associated risk factors are hypertension and diabetes mellitus. The aim of this study was to determine platelet and endothelial activation in patients with recent SDI in comparison to population-based control subjects matched for age, sex and vascular risk factors.
  
  
  METHODS
  Platelet activation markers (activated glycoprotein IIb/IIIa, P-selectin and platelet microparticles), shear-induced platelet aggregation (SIPA) studied in the SIPAgreg device at 4,000 s(-1), endothelial activation markers [including von Willebrand factor (vWF) antigen and homocysteine] and high-sensitivity C-reactive protein (hsCRP) were measured in 74 consecutive patients with recent SDI, in whom detectable large artery atherosclerosis or cardiac embolism had been ruled out. Blood samples were collected 1 and 3 months after symptom onset. These factors were also measured in 74 population-based controls with no stroke history and matched for age, sex, hypertension and diabetes.
  
  
  RESULTS
  One month after symptom onset, the patients had similar levels of platelet activation to matched controls (p > 0.40 for all comparisons). In contrast, endothelial activation parameters were increased in patients in comparison to controls (vWF: p = 0.002 and homocysteinemia/creatinemia: p = 0.025). The level of hsCRP was slightly increased in patients compared to controls (p = 0.059). At 3 months, we observed a significant decrease in vWF and hsCRP levels in patients (median change in vWF = 10%, p = 0.004; median change in hsCRP = 0.4 mg/l, p = 0.02). Homocysteine levels and all platelet parameters remained unchanged at this time compared to at 1 month.
  
  
  CONCLUSIONS
  Our results confirm that chronic platelet activation, when compared to controls matched for age, sex and vascular risk factors, did not seem to play a central role in the pathophysiology of lacunar stroke. In contrast, we found markers of endothelial dysfunction, the role of which in the occurrence of lacunar infarction has still to be clarified in further studies.
authors.affiliation: INSERM U-698, AP-HP, Bichat-Claude Bernard Hospital, University Paris Diderot, Paris, France.
authors.forename: Philippa C
authors.initials: PC
authors.lastname: Lavallée
authors.forename: Julien
authors.initials: J
authors.lastname: Labreuche
authors.forename: Dorothée
authors.initials: D
authors.lastname: Faille
authors.forename: Marie-Geneviève
authors.initials: MG
authors.lastname: Huisse
authors.forename: Pascale
authors.initials: P
authors.lastname: Nicaise-Roland
authors.forename: Monique
authors.initials: M
authors.lastname: Dehoux
authors.forename: Fernando
authors.initials: F
authors.lastname: Gongora-Rivera
authors.forename: Arturo
authors.initials: A
authors.lastname: Jaramillo
authors.forename: David
authors.initials: D
authors.lastname: Brenner
authors.forename: Dominique
authors.initials: D
authors.lastname: Deplanque
authors.forename: Isabelle F
authors.initials: IF
authors.lastname: Klein
authors.forename: Pierre-Jean
authors.initials: PJ
authors.lastname: Touboul
authors.forename: Eric
authors.initials: E
authors.lastname: Vicaut
authors.forename: Nadine
authors.initials: N
authors.lastname: Ajzenberg
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000378:metabolism; D002097:C-Reactive Protein / Q000378:metabolism; D059345:Cerebral Small Vessel Diseases / Q000097:blood* / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D019007:P-Selectin / Q000378:metabolism; D015539:Platelet Activation / Q000502:physiology*; D010974:Platelet Aggregation / Q000502:physiology; D012307:Risk Factors; D020521:Stroke / Q000503:physiopathology; D014841:von Willebrand Factor / Q000378:metabolism
chemical_list: D015415:Biomarkers; D019007:P-Selectin; D014841:von Willebrand Factor; D002097:C-Reactive Protein