Activation of the renin-angiotensin-aldosterone system, through secretion of renin and renin precursors from adipocytes,51 appears to be the main mediator in obesity, although other mechanisms have been postulated.49 While GHF may be a good marker of generalized vascular dysfunction in patients with these conditions, and so might, therefore, be predictive of future cardiovascular events, it was surprising to see that even in healthy participants the presence of GHF could improve cardiovascular risk estimation. This evidence concerns the gene REN and obesity due to melanocortin 4 receptor deficiency.