title: Decreased heparin cofactor II activity is associated with impaired endothelial function determined by brachial ultrasonography and predicts cardiovascular events.
abstract: BACKGROUND
  Heparin cofactor II (HCII) could inactivate thrombin after binding to dermatan sulfate at injured arterial walls, and has been shown to be a novel and independent antiatherosclerotic factor. However, the relation between plasma HCII activity and peripheral vascular endothelial function remains unclear.
  
  
  METHODS
  A total of 199 patients (mean age, 63+/-14 years) were enrolled and followed up for a median period of 24 months. Endothelial function was assessed using brachial ultrasonography to determine endothelium dependent flow-mediated vasodilation (FMD). Cox regression analyses were conducted for the 199 subjects, with cardiovascular events being defined as myocardial infarction (MI), percutaneous coronary intervention (PCI), coronary artery bypass grafting (CABG), ischemic stroke, and peripheral artery revascularization.
  
  
  RESULTS
  A total of 31 patients (16%) had cardiovascular events. Patients with cardiovascular events had significantly lower HCII activity (112+/-34 versus 127+/-34%, p=0.027) and lower antithrombin III (ATIII) activity (82+/-12 versus 88+/-13%, p=0.014) than those without events. By multivariate analysis, age (p=0.012), hsCRP (p=0.020) and HCII activity (p=0.035) were correlated with FMD. Kaplan-Meier analysis was performed and showed plasma HCII (p=0.036) and ATIII activities (p=0.005) were predictors of cardiovascular events. By Cox regression analysis, plasma HCII activity (p=0.026) could be an independent predictor of future cardiovascular events, but not ATIII.
  
  
  CONCLUSIONS
  The present study demonstrates that plasma HCII activity is positively correlated with endothelial vasodilator function. Furthermore, plasma HCII activity could be a predictor of future cardiovascular events in patients with suspected coronary artery disease, suggesting its role in atherosclerosis.
authors.affiliation: Division of Cardiology, Department of Internal Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Po-Hsun
authors.initials: PH
authors.lastname: Huang
authors.forename: Hsin-Bang
authors.initials: HB
authors.lastname: Leu
authors.forename: Jaw-Wen
authors.initials: JW
authors.lastname: Chen
authors.forename: Tao-Cheng
authors.initials: TC
authors.lastname: Wu
authors.forename: Tse-Min
authors.initials: TM
authors.lastname: Lu
authors.forename: Philip
authors.initials: P
authors.lastname: Yu-An Ding
authors.forename: Shing-Jong
authors.initials: SJ
authors.lastname: Lin
mesh_terms: D000368:Aged; D001916:Brachial Artery / Q000000981:diagnostic imaging* / Q000503:physiopathology*; D003324:Coronary Artery Disease / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000503:physiopathology*; D005260:Female; D015844:Heparin Cofactor II / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D014463:Ultrasonography; D014664:Vasodilation
chemical_list: D015844:Heparin Cofactor II