Lacunar stroke accounts for 25% of all ischemic strokes and is characterized by small infarcts located in the deep white matter, basal ganglia or pons resulting from the occlusion of deep branch arteries. In the last years, evidences about the role of endothelial dysfunction in lacunar stroke also named cerebral small vessel disease, have emerged. However platelet activation and aggregation are of major importance in acute thrombosis of atherosclerotic arteries, but their role and that of thrombus formation at sites of arteriolar injury as a precipitating event of lacunar stroke remains unclear.
The aim of the present study was to determine platelet and endothelial activation in consecutive patients with recent lacunar stroke in comparison to population-based control subjects matched for age, sex and vascular risk factors.
Platelet activation markers include activated glycoprotein (GP) IIbIIIa, P-selectin expression, platelet microparticles determined by flow cytometry, shear-induced platelet aggregation (SIPA), measured in a Sipagreg device that reproduces rheological conditions of stenotic or small arteries. We also studied endothelial activation markers including von Willebrand factor antigen (vWF), homocystein and high sensitivity C-reactive Protein (hsCRP). All these parameters were measured in 74 consecutive patients with recent lacunar stroke, in whom detectable large artery atherosclerosis or cardiac embolism have been ruled out, and in 74 population-based controls with no stroke history, matched for age, sex, hypertension, and diabetes. All patients were treated by anti-aggregant therapy, 15 (20%) were treated by clopidogrel (75 mg/d) and the remaining 59 cases received only acetylsalicylic acid (75 to 160 mg/d). Repeated blood samples were collected at one- and three-months after symptom onset.
One month after symptom onset, patients had similar levels of platelet activation compared to matched controls (p>0.40 for all-comparisons), including platelet membrane P-selectin with a median value of 1.3% and an interquartile range (IQR) (0.7–2.8) in patients and 1.1% (0.6–2.2) in controls, p=0.37), platelet activated GPIIbIIIa reached 2.9% (0.9–6.7) in patients and 2.8% (0.7–10.2) in controls, p=0.94. Platelet-derived microparticles were 5067/μL of blood (3720–7490) and 5035 (3530–8150) p=0.63l, in patients and controls, respectively. SIPA values at 4000 sec-1 were in the normal range in patients and controls, with no difference between the two groups: the median value of platelet aggregation was 22% (12–37%) in cases and 23% (7–45%) in controls (p=0.96), respectively. Endothelial activation parameters were increased in patients in comparison to controls (vWF p=0.002 and homocystein/creatinemia p=0.025) The median value of vWF antigen was 142% (114–182%) in cases and 122% (97–150%) in controls (p=0.002). The median value of ratio homocysteinemia/creatinemia was 0.151 (0.119–0.187) in cases and 0.134 (0.111–0.165) in controls (p=0.025). The median value of hsCRP was 2.7 mmol/l (1.5–6.0) in cases and 2.0 mmol/l (1.0–3.4) in controls (p=0.059). Level of hsCRP was slightly increased in patients compared to controls (p=0.059). At 3 months, significant decrease in vWF and hsCRP levels (median change in vWF=10%, p=0.004; median change in hsCRP=0.4 mg/L, p=0.02) was detected in patients. Homocystein level and all platelet parameters remained unchanged at this time compared to 1 month.
Our results confirm that endothelial dysfunction is a major feature of lacunar stroke. One explanation could be an endothelial response to an acute systemic aggression by an unidentified agent. In contrast, 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.
No relevant conflicts of interest to declare.
Asterisk with author names denotes non-ASH members.