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MULTIPLE ANABOLIC DEFICIENCY IN MEN WITH CHRONIC HEART FAILURE
Ewa A. Jankowska
Cardiology Department, Military Hospital, Wroclaw, Poland, Institute
of Anthropology, Polish Academy of Sciences, Wroclaw, Poland,
National Heart & Lung Institute, Imperial College London, UK e.jankowska@imperial.ac.uk
Chronic heart failure (CHF), a disease characterised by fatal prognosis
and poor quality of life, has traditionally been linked to malfunction
of the heart as a pump. There is now mounting evidence to show that
the complex pathophysiology of CHF begins with an abnormality of
the heart, but involves peripheral mechanisms and dysfunction of
most body organs, including the cardiovascular, musculoskeletal,
renal, neuroendocrine, haemostatic, and immune systems.
We have prospectively studied the prevalence, clinical and prognostic
consequences of anabolic deficiencies within 3 major endocrine axes
(gonadal, adrenal, and somatotropic) in a cohort of around 300 men
with stable systolic CHF. Deficiencies in circulating total testosterone
(TT), dehydroepiandrosterone sulphate (DHEAS) and insulin-like growth
factor type 1 (IGF-1) (defined as = the 10th percentile of values
for age-matched healthy controls) are prevalent across all age categories
in approximately 30%, 60% and 80% of men with CHF, respectively.
Reduced serum levels of TT, DHEAS and IGF-1 independently predict
high long-term mortality in a cohort of men with CHF, even after
adjustment for other previously established prognosticators, markers
of disease severity (high NYHA class, low ejection fraction, increased
plasma levels of natriuretic peptides), concomitant treatment, and
co-morbidities. Men with CHF and normal levels of all anabolic hormones
have the lowest 3-year mortality rate (17%, 95%CI: 2-33%) compared
with those with deficiencies in one (26%, 95%CI: 16-35%), two (45%,
95%CI: 34-55%), or all three (73%, 95%CI: 51-95%) anabolic axes.
The higher the number of deficient anabolic hormones, the worse
the prognosis. In men with CHF, reduced serum TT constitutes an
independent major determinant of impaired exercise capacity (reduced
peak oxygen consumption and reduced distance during a 6-minute walk
test), lower muscle strength and lower lean tissue mass, and reduced
haemoglobin level. Deficiency in serum TT and DHEAS, irrespectively
of disease severity, are linked to poor quality of life, and more
intense depressive and andropausal symptoms in these patients.
In conclusion, anabolic hormone depletion is common in men with CHF,
and multiple anabolic deficiency predicts increased long-term mortality.
Moreover, anabolic deficiency is linked to exercise intolerance,
deranged body composition, poor quality of life, and depressive
symptoms in men with CHF. The origin of anabolic deficiency in CHF
is enigmatic, albeit it is presumed that insulin resistance and
augmented inflammation may be involved. Moreover, precise mechanisms
underlying protective effects of anabolic signalling in men with
CHF remain unclear. Our results constitute premises to consider
hormone derangements as important clinical targets for pharmacological
interventions in anabolic deficient patients. Whether men with CHF
with anabolic deficiency would benefit from hormone supplementation,
needs to be further studied.
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