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(Circulation. 2004;109:481-486.)
© 2004 American Heart Association, Inc.

Clinical Investigation and Reports

High Plasma Heparin Cofactor II Activity Is Associated With Reduced Incidence of In-Stent Restenosis After Percutaneous Coronary Intervention

Nobuyuki Takamori, MD; Hiroyuki Azuma, MD; Midori Kato, MD; Shunji Hashizume, MD; Ken-ichi Aihara, MD; Masashi Akaike, MD; Katsuya Tamura, MD; Toshio Matsumoto, MD

From the Department of Medicine and Bioregulatory Sciences, University of Tokushima Graduate School of Medicine, Tokushima (N.T., H.A., M.K., S.H., K.A., M.A., T.M.), and Department of Cardiology, Health Insurance Naruto Hospital, Naruto (K.T.), Japan.

Correspondence to Hiroyuki Azuma, MD, Department of Medicine and Bioregulatory Sciences, University of Tokushima Graduate School of Medicine, 3-18-15 Kuramoto-cho, Tokushima 770-8503, Japan. E-mail hiroyuki{at}clin.med.tokushima-u.ac.jp

Received February 12, 2003; de novo received September 16, 2003; revision received October 24, 2003; accepted October 30, 2003.

Background— Thrombin plays an important role in the development of atherosclerosis and restenosis after percutaneous coronary intervention. Because heparin cofactor II (HCII) inhibits thrombin action in the presence of dermatan sulfate, which is abundantly present in arterial wall, HCII may affect vascular remodeling by modulating thrombin action. We hypothesized that patients with high plasma HCII activity may show a reduced incidence of in-stent restenosis (ISR).

Methods and Results— Sequential coronary arteries (n=166) with NIR stent (Boston Scientific Corp) implantation in 134 patients were evaluated before, immediately after, and at 6 months after percutaneous coronary intervention. Patients were divided into the following groups: high HCII (110%, 45 lesions in 36 patients), normal HCII (80% and <110%, 81 lesions in 66 patients), and low HCII (<80%, 40 lesions in 32 patients). Percent diameter stenosis at follow-up in the high-HCII group (18.7%) was significantly lower (P=0.046) than that in the normal-HCII group (30.3%) or the low-HCII group (29.0%). The ISR rate in the high-HCII group (6.7%) was significantly lower than that in the low-HCII group (30.0%) (P=0.0039). Furthermore, multivariate analysis demonstrated that high plasma HCII activity is an independent factor in reducing the incidence of angiographic restenosis (odds ratio, 0.953/1% increase of HCII; 95% CI, 0.911 to 0.998).

Conclusions— The results demonstrate that HCII may have a hitherto unrecognized effect in inhibiting ISR. The effect of HCII may be mediated by inactivating thrombin in injured arteries, thereby inhibiting vascular smooth muscle cell migration and proliferation.

Key Words: cardiovascular diseases • angioplasty • atherosclerosis • thrombin • dermatan sulfate

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