Published Online
on May 17, 2004

A more recent version of this article appeared on June 8, 2004

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Submitted on October 14, 2003
Revised on January 7, 2004
Accepted on March 1, 2004

Heparin Cofactor II Is a Novel Protective Factor Against Carotid Atherosclerosis in Elderly Individuals

Ken-ichi Aihara MD, Hiroyuki Azuma MD, PhD^*, Nobuyuki Takamori MD, Yasuhiko Kanagawa MD, PhD, Masashi Akaike MD, PhD, Mitsunori Fujimura MD, Tomonori Yoshida MD, Shunji Hashizume MD, Midori Kato MD, Hiroshi Yamaguchi MD, PhD, Shuji Kato MD, Yasumasa Ikeda MD, Tomoko Arase MD, PhD, Akira Kondo MD, PhD, and Toshio Matsumoto MD, PhD

From the Department of Medicine and Bioregulatory Sciences, University of Tokushima; Graduate School of Medicine, Kuramoto-cho Tokushima, Japan (K.A., H.A., N.T., Y.K., M.A., M.F., T.Y., S.H., M.K., H.Y., S.K., Y.I., T.M.); and Kondo Naika Hospital, Nishi-shinhama-cho Tokushima, Japan (K.A., S.K., T.A., A.K.).

^* To whom correspondence should be addressed. E-mail: hiroyuki{at}clin.med.tokushima-u.ac.jp.

Background--Thrombin plays a crucial role in atherothrombotic changes. Because heparin cofactor II (HCII) inhibits thrombin actions after binding to dermatan sulfate at injured arterial walls, HCII may negatively regulate thrombin actions in vascular walls. We hypothesized that plasma HCII activity is a preventive factor against atherosclerotic changes, especially in elderly individuals who already have atherosclerotic vascular injuries.

Methods and Results--Maximum plaque thickness (MPT) in the carotid artery was measured by ultrasonography in 306 Japanese elderly individuals (154 men and 152 women; age, 40 to 91 years; 68.9±11.1 years, mean±SD). The relevance of cardiovascular risk factors including plasma HCII activity to the severity of MPT was statistically evaluated. Plasma HCII activity decreased with age. Simple linear regression analysis after adjustments for age and sex showed that lipoprotein(a), glycosylated hemoglobin A1c, and presence of diabetes mellitus significantly contributed to an increase in MPT values (r=0.119, P<0.05; r=0.196, P<0.001; and r=0.227, P<0.0001, respectively). In contrast, high-density lipoprotein (HDL) cholesterol and HCII activity were negatively correlated with MPT values (r=-0.117, P<0.05, and r=-0.202, P<0.0005, respectively). Multiple regression analysis revealed that plasma HCII activity and HDL cholesterol independently contributed to the suppression of MPT values and that the antiatherogenic contribution of HCII activity was stronger than that of HDL cholesterol (P<0.001 and P<0.05, respectively).

Conclusions--These results suggest that HCII can be a novel and independent antiatherogenic factor. Moreover, HCII is a stronger predictive factor than HDL cholesterol against carotid atherosclerosis in elderly individuals.

Key words: atherosclerosis • carotid arteries • ultrasonics • thrombin • heparin

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