Thirdly, obesity has been shown to impact circulating levels of neurohormones and cytokines related to HF pathogenesis.14 As examples, tumor necrosis factor alpha has been associated with cardiac cachexia and was inversely correlated with BMI15; increase in plasma adiponectin levels (related with increase in risk of mortality) are inversely correlated with BMI.16 High BMI might attenuate the release of detrimental circulating mediators once cardiovascular disease is present. This evidence concerns the gene TNF and obesity due to melanocortin 4 receptor deficiency.