Inappropriately low plasma leptin concentration in the cachexia associated with chronic heart failure

Background-Cardiac cachexia is a syndrome of generalised wasting which caries a poor prognosis and is associated with raised plasma concentrations of tumour necrosis factor alpha (TNF alpha). TNF alpha increases secretion of leptin, a hormone which decreases food intake and increases energy expenditure. Objective-To determine whether an inappropriate increase in plasma leptin concentration contributes to the cachexia of chronic heart failure. Design-Retrospective case-control study. Setting-Tertiary referral cardiology unit. Patients-110 human subjects comprising 29 cachectic chronic heart failure patients, 22 non-cachectic chronic heart failure patients, 33 patients with ischaemic heart disease but normal ventricular function, and 26 healthy controls. Interventions-Measurement of: body fat content by skinfold thickness (cachectic males < 27%, females < 29%); plasma leptin, TNF alpha, and noradrenaline (norepinephrine); central haemodynamics in chronic heart failure patients at right heart catheterisation. Main outcome measures-Plasma leptin concentration corrected for body fat content, plasma TNF alpha and noradrenaline concentration, and central haemodynamics. Results-Mean (SEM) plasma leptin concentrations were: 6.2 (0.6) ng/ml (cachectic heart failure), 16.9 (3.6) ng/ml (non-cachectic heart failure), 16.8 (3.0) ng/ml (ischaemic heart disease), and 18.3 (3.5) ng/ml (control) (p < 0.001 for cachectic heart failure v all other groups). Plasma leptin concentration remained significantly lower in the cachectic heart failure group even after correcting for body fat content and in spite of significantly increased TNF alpha concentrations. Thus plasma leptin was inappropriately low in cachectic chronic heart failure in the face of a recognised stimulus to its secretion. There was no significant correlation between plasma leptin, New York Heart Association class, election fraction, or any haemodynamic indices. Conclusions-Leptin does not contribute to the cachexia of chronic heart failure. One or more leptin suppressing mechanisms may operate in this syndrome-for example, the sympathetic nervous system.