Background and Purpose— Endothelial progenitor cells (EPCs) migrate from bone marrow to systemic circulation in response to tissue ischemia where they differentiate into mature endothelial cells for angiogenesis in situ. This study tested the hypothesis that the level of circulating EPCs is substantially increased and predictive of prognostic outcomes after acute ischemic stroke (IS). Methods— The level of circulating EPCs (staining markers: CD31/CD34 [E 1 ], CD62E/CD34 [E 2 ], and KDR/CD34 [E 3 ]) were examined using flow cytometry at 48 hours after acute IS in 138 consecutive patients. The EPC level was also evaluated once in 20 healthy volunteers and in 40 at-risk control subjects. Results— Level of circulating EPCs (E 1–3 ) was significantly higher in patients with IS than in at-risk control subjects ( P <0.05). Additionally, EPC (E 1–3 ) level was significantly lower in patients with severe neurological impairment (defined as a score ≥12 on the National Institutes of Health Stroke Scale) than in patients with less severe impairment (National Institutes of Health Stroke Scale < score 12) at 48 hours after IS ( P <0.0001). Moreover, the EPC (E 3 ) level was strongly correlated with improved National Institutes of Health Stroke Scale ≥4 on day 21 after IS ( P =0.0004). Furthermore, low circulating EPC level was independently predictive of severe neurological impairment (National Institutes of Health Stroke Scale ≥12) at 48 hours (E 1–3 ) and combined major adverse clinical outcomes (defined as recurrent IS, any cause of death, or National Institutes of Health Stroke Scale of ≥12) on day 90 (E 1 ) after IS ( P <0.001). Conclusions— Level of circulating EPCs is independently predictive of prognosis after IS.

Platelet activation was significantly increased in acute ischemic stroke and substantially decreased thereafter. The lesser long-term pharmacodynamic potency of aspirin relative to clopidogrel raises the prospect of the need for more effective antiplatelet agents or a synergistic combination therapy for stroke prevention in the future.

Background: Platelets play an important role in atherosclerosis and thromboembolic events. We examined the relationship between platelet activity and outcomes after an ischemic stroke. Methods: Using flow cytometry, we serially measured the fractions of circulating platelet activity (CD62p expression) after an ischemic stroke in early (<48 h), recent (day 7), convalescent (day 21) and chronic (day 90) phases in 92 consecutive patients with an ischemic stroke. Patients were classified into high (CD62p expression >3.16%) and low (CD62p expression ≤3.16%) platelet activity groups according to the median value of CD62p expression in the early phase of a stroke. Results: The composite end point – death, recurrent stroke and severe neurological impairment (alive in care), defined as a score of >13 on the National Institutes of Health Stroke Scale – within the first 30 days and at an interval of 8.2 ± 1.5 months of follow-up was determined for each group. In the first 30 days, the composite end point occurred in 37.0% of patients in the high platelet activity group as compared with 6.5% in the low platelet activity group (p = 0.0004). At a mean follow-up of 8.2 ± 1.5 months, the composite end point occurred in 36.6% of patients in the high platelet activity group as compared with 10.9% in the low platelet activity group (p = 0.0044). Multiple stepwise logistic regression analysis displayed that high platelet activity (p = 0.011), age (p = 0.013) and the presence of coronary artery disease (p = 0.021) were independently associated with adverse outcomes at the intermediate-term follow-up. Conclusions: Results of this study showed that high platelet activity is strongly associated with adverse clinical outcomes after an early ischemic stroke.

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