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 (TNFalpha). TNFalpha 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.


METHODS
Retrospective case-control study.


METHODS
Tertiary referral cardiology unit.


METHODS
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.


METHODS
Measurement of: body fat content by skinfold thickness (cachectic males < 27%, females < 29%); plasma leptin, TNFalpha, and noradrenaline (norepinephrine); central haemodynamics in chronic heart failure patients at right heart catheterisation.


METHODS
Plasma leptin concentration corrected for body fat content, plasma TNFalpha 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 TNFalpha 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, ejection 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.
Murdoch
D R
DR
Department of Cardiology, Western Infirmary, Dumbarton Road, Glasgow G11 6NT, UK. drm2x@udcf.gla.ac.uk
Rooney
E
E
Dargie
H J
HJ
Shapiro
D
D
Morton
J J
JJ
McMurray
J J
JJ
D000273:Adipose Tissue / Q000473:pathology; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D015992:Body Mass Index; D002100:Cachexia / Q000097:blood* / Q000209:etiology; D016022:Case-Control Studies; D002908:Chronic Disease; D005260:Female; D006333:Heart Failure / Q000097:blood / Q000150:complications* / Q000473:pathology; D006439:Hemodynamics; D006801:Humans; D020738:Leptin; D008297:Male; D008875:Middle Aged; D009638:Norepinephrine / Q000097:blood; D011506:Proteins / Q000378:metabolism*; D012189:Retrospective Studies; D012720:Severity of Illness Index; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D015415:Biomarkers; D020738:Leptin; D011506:Proteins; D014409:Tumor Necrosis Factor-alpha; D009638:Norepinephrine