As a matter of fact, prolonged administration of PDE5i in diabetic patients with or without ED has been shown to improve surrogate markers of endothelial dysfunction, such as flow mediated dilatation, and reduce serum indices of vascular inflammation.12,39,40 At a clinical level, a generalized improvement of endothelial function promoted by PDE5 inhibition in patients with an elevated cardiovascular risk may be responsible for the substantial decrease in MACE that was observed in our analysis. Here, PDE5A is linked to endothelial dysfunction.