Increased levels of circulating endothelial progenitor cells in patients with ischaemic stroke treated with statins during acute phase

Abstract

Background and purpose: Endothelial progenitor cells (EPCs) have been suggested to be a therapeutic option in ischaemic stroke. Our aim was to study whether statin treatment during acute phase could increase circulating EPCs after acute ischaemic stroke.

Methods: We studied 48 patients with a first-ever non-lacunar ischaemic stroke (<12 h from stroke onset). Sixteen patients received statin treatment (20 mg atorvastatin/day) during the first 4 days. We defined the EPC increment during the first week as the difference in the number of early outgrowth colony-forming unit-endothelial cell (CFU-EC) between day 7 and at admission (previous to atorvastatin treatment). Serum levels of vascular endothelial growth factor and active matrix metalloproteinase 9 (determined by ELISA), and nitric oxide metabolites (NOx) (determined by high-performance liquid chromatography) were measured at admission, 24 and 72 h, and day 7.

Results: Colony-forming unit-endothelial cells were similar at baseline between patients treated (n = 16) and non-treated (n = 32) with statins (10.1 ± 3.9 vs. 7.9 ± 6.9 CFU-EC, P = 0.223). However, patients treated with statins showed a higher EPC increment (24.0 ± 17.3 vs. 6.0 ± 17.8 CFU-EC, P = 0.002) during the first week. An EPC increment ≥ 4 CFU-EC predicted with the highest sensitivity (88%) and specificity (92%) the probability of good outcome (area under the curve 0.903, P < 0.0001). Statin treatment (OR, 13.1; CI 95%, 2.2-76.9, P = 0.004) was independently associated with an EPC increment ≥ 4 CFU-EC after adjustment for confounder factors, but this association was lost when adjusting for NOx levels.

Conclusions: Statin treatment for 4 days may increase circulating EPC levels, probably by NO-related mechanisms.