The derangement of neuro-endocrine control of circulation influences both 
disease evolution and response to treatment in patients with heart failure, but 
little data are available about the complex relationships between the degree of 
neuro-hormonal activation and clinical severity. We studied the relationships 
between cardiac natriuretic hormones (CNHs) and several neuro-hormones and 
immunological markers in a prospective cohort of 105 consecutive patients with 
cardiomyopathy (77 men and 28 women, mean age 66.7+/-12.4 years, range 33-89 
years). We assayed the circulating levels of CNHs (atrial natriuretic peptide 
(ANP) and brain natriuretic peptide (BNP)), plasma renin activity (PRA), 
aldosterone, cortisol, adrenaline, noradrenaline, thyroid hormones and thyroid 
stimulating hormone (TSH), tumour necrosis factor-alpha (TNF-alpha) and 
interleukin-6 (IL-6). The concentrations of all CNHs and neurohormones were 
higher in patients with heart failure compared to normal subjects, except for 
free triiodothyronine (FT3), which was below normal values. ANP was positively 
related to NYHA class, IL-6, adrenaline, noradrenaline and cortisol, while 
negatively with ejection fraction and FT3. BNP was positively related to age, 
NYHA class, IL-6, TNF-alpha, adrenaline, noradrenaline and cortisol, while 
negatively with ejection fraction and FT3. A stepwise multiple linear regression 
indicated that plasma ANP depended only on ejection fraction, adrenaline and 
noradrenaline values, while for plasma BNP variation NYHA class contributed too. 
Our data confirm a progressive activation of hormonal and immunological systems 
in patients with heart failure. Furthermore, CNH circulating levels in heart 
failure are affected not only by cardiac function and disease severity, but also 
by activation of neuro-hormonal and stress-related cytokine systems, as well as 
by the thyroid hormones, even on usual medical treatment.