Department of Metabolism, Endocrinology and Molecular Medicine, Osaka City University Graduate School of Medicine, Osaka, Japan.
J Atheroscler Thromb. 2011;18(10):883-90. doi: 10.5551/jat.9225. Epub 2011 Jun 24.
A recent clinical trial showed the preventive effect of cilostazol on cerebrovascular diseases. We compared the effects of cilostazol with aspirin on circulating endothelial progenitor cells (EPCs), a surrogate marker for cardiovascular disease, and lipid metabolism in a randomized controlled trial (UMIN000000537).
Forty-nine diabetic outpatients with leukoaraiosis or asymptomatic old cerebral infarction were enrolled in the study with written informed consent. They were randomly assigned to a cilostazol (200 mg daily, n= 24) or aspirin group (100 mg daily, n= 25), and followed for 16 weeks. Changes in circulating CD34(+) CD45(low) CD133(+) VEGFR2(+) EPCs (ΔEPC) were a primary endpoint. Changes in CD34(+) CD45(low) CD133(+) progenitor cells (ΔPC), p-selectin-positive platelet, platelet-monocyte binding measured by flow cytometry, LDL-, HDL-, small dense LDL (sdLDL)-cholesterol and triacylglycerol were the secondary endpoints.
Twenty patients in each group completed the study. ΔEPC were significantly higher in the cilostazol group than aspirin group at 16 weeks, while ΔPC were already significantly higher at 4 weeks in the cilostazol group. Changes in p-selectin-positive platelets and platelet-monocyte binding were similar in both groups. The cilostazol group showed significantly less sdLDL- and higher HDL-cholesterol than the aspirin group at both 4 and 16 weeks. ΔEPC were significantly and inversely correlated with changes of sdLDL, while positively with those of HDL. Analysis of covariance showed that a significant relation of ΔEPCs with cilostazol treatment was confounded by changes in HDL- and sdLDL-cholesterol.
Cilostazol increases circulating EPCs and decreases small-dense LDL in diabetic patients with cerebral ischemia.
最近的一项临床试验表明，西洛他唑具有预防脑血管疾病的作用。我们在一项随机对照试验（UMIN000000537）中比较了西洛他唑与阿司匹林对循环内皮祖细胞（EPCs）的影响，EPCs 是心血管疾病的替代标志物，以及脂质代谢。
49 例伴有脑白质疏松症或无症状陈旧性脑梗死的糖尿病患者在知情同意的情况下入组本研究。他们被随机分为西洛他唑组（每天 200mg，n=24）或阿司匹林组（每天 100mg，n=25），并随访 16 周。循环 CD34(+) CD45(low) CD133(+) VEGFR2(+) EPCs（ΔEPC）的变化为主要终点。CD34(+) CD45(low) CD133(+)祖细胞（ΔPC）、流式细胞术检测的 p-选择素阳性血小板、血小板-单核细胞结合、LDL-、HDL-、小而密 LDL（sdLDL）-胆固醇和三酰甘油的变化为次要终点。
每组 20 例患者完成了研究。16 周时，西洛他唑组的ΔEPC 明显高于阿司匹林组，而 4 周时西洛他唑组的ΔPC 明显升高。两组 p-选择素阳性血小板和血小板-单核细胞结合的变化相似。西洛他唑组在 4 周和 16 周时 sdLDL-胆固醇和 HDL-胆固醇均明显低于阿司匹林组。ΔEPC 与 sdLDL 的变化呈显著负相关，与 HDL 的变化呈显著正相关。协方差分析显示，ΔEPC 与西洛他唑治疗的关系受到 HDL 和 sdLDL-胆固醇变化的混杂。
西洛他唑增加了糖尿病脑缺血患者的循环 EPCs 并降低了小而密 LDL。
