Elevated circulating level of ghrelin in cachexia associated with chronic heart failure: relationships between ghrelin and anabolic/catabolic factors.

BACKGROUND Ghrelin is a novel growth hormone (GH)-releasing peptide, isolated from the stomach, that may also cause a positive energy balance by stimulating food intake and inducing adiposity. We sought to investigate the pathophysiology of ghrelin in the cachexia associated with chronic heart failure (CHF). METHODS AND RESULTS Plasma ghrelin was measured in 74 patients with CHF and 12 control subjects, together with potentially important anabolic and catabolic factors, such as GH and tumor necrosis factor (TNF-alpha). Patients with CHF were divided into two groups, those with cachexia (n=28) and those without cachexia (n=46). Plasma ghrelin did not significantly differ between all CHF patients and controls (181+/-10 versus 140+/-14 fmol/mL, P=NS). However, plasma ghrelin was significantly higher in CHF patients with cachexia than in those without cachexia (237+/-18 versus 147+/-10 fmol/mL, P<0.001). Circulating GH, TNF-alpha, norepinephrine, and angiotensin II were also significantly higher in CHF patients with cachexia than in those without cachexia. Interestingly, plasma ghrelin correlated positively with GH (r=0.28, P<0.05) and TNF-alpha (r=0.31, P<0.05) and negatively with body mass index (r=-0.35, P<0.01). CONCLUSIONS Plasma ghrelin was elevated in cachectic patients with CHF, associated with increases in GH and TNF-alpha and a decrease in body mass index. Considering ghrelin-induced positive energy effects, increased ghrelin may represent a compensatory mechanism under catabolic-anabolic imbalance in cachectic patients with CHF.