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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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The rationale for combination builds upon the documented mechanisms of each component

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