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

Abstract

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/m 2 ). 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.