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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2005;25:617.)
© 2005 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Circulating Insulin-Like Growth Factor-1 and Insulin-Like Growth Factor Binding Protein-3 Are Associated With Early Carotid Atherosclerosis

Shin-ichi Kawachi; Noriyuki Takeda; Akihiko Sasaki; Yoshiaki Kokubo; Kazuhisa Takami; Hiroshi Sarui; Makoto Hayashi; Noriyoshi Yamakita; Keigo Yasuda

From the Department of Diabetes and Endocrinology (S.K., A.S., Y.K., K.T.), Medical Sciences Graduate School of Medicine, Gifu University, the Department of Endocrinology and Metabolism (N.T., H.S.), Murakami Memorial Hospital, Asahi University, and the Department of Internal Medicine (M.H., N.Y., K.Y.), Matsunami General Hospital, Gifu, Japan.

Correspondence to Shin-ichi Kawachi, Department of Diabetes and Endocrinology, Medical Sciences Graduate School of Medicine, Gifu University, 1-1 Yanagido, Gifu 501-1194, Japan. E-mail kawachi{at}cc.gifu-u.ac.jp

Objective— Growth hormone (GH)–insulin-like growth factor (IGF)-1 axis regulates growth and survival of vascular cells and cardiomyocytes. The role of GH–IGF-1 axis in cardiovascular disease is controversial.

Methods and Results— We assessed the association of circulating levels of IGF-1 and IGF binding protein-3 (IGFBP-3) with early carotid atherosclerosis and atherosclerotic risk factors in 330 Japanese men (age 51.6±8.6 years, range 29 to 77, body mass index [BMI] 23.6±2.9 kg/m²). Intima-media thickness (IMT) of the common carotid artery was measured by ultrasound. Abdominal visceral adipose and subcutaneous adipose tissue area by computer-assisted tomographic scan were determined. Correlation coefficients were calculated by partial correlation analysis. BMI and plasma insulin showed positive associations with circulating IGF-1 and IGFBP-3. Subcutaneous adipose tissue was correlated with IGF-1. High-density lipoprotein cholesterol was inversely associated with IGF-1. Blood pressure, total cholesterol, triglyceride, and visceral adipose tissue were positively associated with IGFBP-3. IGF-1 and IGFBP-3 were associated with carotid IMT independent of age, BMI, blood pressure, and insulin. Insulin was associated with carotid IMT in univariate analysis. However, it was not correlated with carotid IMT in the multivariate analyses which included IGF-1 or IGFBP-3 as a covariate.

Conclusion— Increased circulating IGF-1 and IGFBP-3 may be stimulators of atherosclerosis.

The role of growth hormone–insulin-like growth factor (IGF)-1 axis in cardiovascular disease is controversial. We have found that IGF-1 and IGF binding protein (IGFBP)-3 were associated with carotid intima-media thickness independent of age, body mass index, blood pressure, and insulin in 330 apparently healthy Japanese men. Circulating IGF-1 and IGFBP-3 may be stimulators of atherosclerosis.

Key Words: insulin-like growth factor-1 • insulin-like growth factor binding protein-3 • atherosclerosis • cardiovascular disease • metabolic syndrome

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