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Indeed, many of the traditional CVD risk factors, including oxidized low-density lipoprotein [313], hyperlipidemia (hypercholesterolemia or mixed dyslipidemia) [314] insulin resistance [309,310,312], diabetes [315], obesity [309,311], elevated C-reactive protein [316], waist-to-hip ratio [309], reduced coronary flow reserve [279], smoking [317], sedentary life [318] and psychological distress [319], which act via effects on endothelial dysfunction, apoptosis and impaired endothelial-dependent vascular reactivity, have been associated with low serum IGF-I levels and reduced IGF-I and IGF-IR mRNA as well as protein expression in vascular smooth muscle cells (VSMC) [313]
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