Anabolic deficiency in men with chronic heart failure - Prevalence and detrimental impact on survival

Background - The age-related decline of circulating anabolic hormones in men is associated with increased morbidity and mortality. We studied the prevalence and prognostic consequences of deficiencies in circulating total testosterone (TT) and free testosterone, dehydroepiandrosterone sulfate (DHEAS), and insulin-like growth factor-1 (IGF-1) in men with chronic heart failure (CHF). Methods and Results - Serum levels of TT, DHEAS, and IGF-1 were measured with immunoassays in 208 men with CHF (median age 63 years; median left ventricular ejection fraction 33%; New York Heart Association class I/II/III/IV, 19/102/70/17) and in 366 healthy men. Serum levels of free testosterone were estimated (eFT) from levels of TT and sex hormone binding globulin. Deficiencies in DHEAS, TT, eFT, and IGF-1, defined as serum levels at or below the 10th percentile of healthy peers, were seen across all age categories in men with CHF. DHEAS, TT, and eFT were inversely related to New York Heart Association class irrespective of cause (all P < 0.01). DHEAS correlated positively with left ventricular ejection fraction and inversely with N-terminal pro-brain natriuretic peptide (both P < 0.01). Circulating TT, eFT, DHEAS, and IGF-1 levels were prognostic markers in multivariable models when adjusted for established prognostic factors (all P < 0.05). Men with CHF and normal levels of all anabolic hormones had the best 3-year survival rate (83%, 95% CI 67% to 98%) compared with those with deficiencies in 1 (74% survival rate, 95% CI 65% to 84%), 2 (55% survival rate, 95% CI 45% to 66%), or all 3 (27% survival rate, 95% CI 5% to 49%) anabolic endocrine axes (P < 0.0001). Conclusions - In male CHF patients, anabolic hormone depletion is common, and a deficiency of each anabolic hormone is an independent marker of poor prognosis. Deficiency of > 1 anabolic hormone identifies groups with a higher mortality.