These include GH-induced volume expansion, overactivity of the renin-angiotensin-aldosterone system, endothelial dysfunction, and increased sympathetic tone (Sharma M et al.)[43]. As has been alluded to by the review by Wolters C et al. [49], the relationship between IGF-1 and cardiovascular disease is non-linear, and the deleterious effects of prolonged excess GH/IGF-1 on the endothelium may not be completely reversed even with disease control. This evidence concerns the gene IGF1 and endothelial dysfunction.