A further related finding was that the accumulation of a variety of cardiovascular comorbidities such as ageing, hypertension, diabetes, obesity and physical inactivity (which limit NO bioavailability and thereby decrease PKG activity in adjacent cardiomyocytes) has been mechanistically linked to the classical hallmarks of LV stiffness and diastolic dysfunction, which include concentric LV remodelling and cardiomyocyte stiffening due to titin hypophosphorylation [1–5, 10, 12, 19, 22]. This evidence concerns the gene PRKG1 and obesity disorder.