Decreased heparin cofactor II activity is associated with impaired endothelial function determined by brachial ultrasonography and predicts cardiovascular events.
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.
Huang
Po-Hsun
PH
Division of Cardiology, Department of Internal Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
Leu
Hsin-Bang
HB
Chen
Jaw-Wen
JW
Wu
Tao-Cheng
TC
Lu
Tse-Min
TM
Yu-An Ding
Philip
P
Lin
Shing-Jong
SJ
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
D015844:Heparin Cofactor II