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.