title: Comparison of the effect of cilostazol with aspirin on circulating endothelial progenitor cells and small-dense LDL cholesterol in diabetic patients with cerebral ischemia: a randomized controlled pilot trial.
abstract: OBJECTIVE
  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).
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  Cilostazol increases circulating EPCs and decreases small-dense LDL in diabetic patients with cerebral ischemia.
authors.affiliation: Department of Metabolism, Endocrinology and Molecular Medicine, Osaka City University Graduate School of Medicine, Osaka, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Ueno
authors.forename: Hidenori
authors.initials: H
authors.lastname: Koyama
authors.forename: Yohei
authors.initials: Y
authors.lastname: Mima
authors.forename: Shinya
authors.initials: S
authors.lastname: Fukumoto
authors.forename: Shinji
authors.initials: S
authors.lastname: Tanaka
authors.forename: Takuhito
authors.initials: T
authors.lastname: Shoji
authors.forename: Masanori
authors.initials: M
authors.lastname: Emoto
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Shoji
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Nishizawa
authors.forename: Masaaki
authors.initials: M
authors.lastname: Inaba
mesh_terms: D000368:Aged; D001241:Aspirin / Q000494:pharmacology*; D002545:Brain Ischemia / Q000150:complications / Q000517:prevention & control*; D008078:Cholesterol, LDL / Q000097:blood*; D000077407:Cilostazol; D003920:Diabetes Mellitus / Q000097:blood*; D004730:Endothelium, Vascular / Q000473:pathology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010865:Pilot Projects; D013777:Tetrazoles / Q000494:pharmacology*
chemical_list: D008078:Cholesterol, LDL; D018696:Neuroprotective Agents; D013777:Tetrazoles; D000077407:Cilostazol; D001241:Aspirin