Dallas, TX - Many men with systolic heart failure have deficiencies in certain anabolic hormones that are associated with significantly increased mortality independent of NYHA class and other risk markers, according to an observational study [1].

The finding suggests a potential for measurements of serum testosterone, dehydroepiandrosterone sulfate (DHEAS), and insulinlike growth factor-1 (IGF-1) to sharpen HF risk assessments based on standard predictors and raises the possibility of anabolic-hormone deficiencies as potential treatment targets, concludes a report from Dr Ewa A Jankowska (Military Hospital, Wroclaw, Poland), published online October 9, 2006 in Circulation and slated for the journal's October 24 issue.

"This is a very intriguing area that has not been very actively investigated in heart failure," Dr Gregg C Fonarow (University of California, Los Angeles), who was not connected to the study, told heartwire. The investigators showed "strong associations" between the hormone deficiencies and HF status, he observed, but whether they are really independent of NYHA class and other standard risk criteria remains an open question. Fonarow noted that the authors were appropriately cautious about making too much of the observational findings, noting that they would need to be confirmed by appropriate trials before there could be any clinical application.

In the study, serum levels of total testosterone (TT), DHEAS, and IGF-1 were obtained from 208 men with chronic HF who were hospitalized or treated as outpatients and from a reference population of 366 men free of chronic disease. Levels of free circulating testosterone (eFT) were estimated as probably a better gauge of the hormone's biologic activity than TT, according to the authors. The patients had an LVEF <45% and were free of other chronic or acute disorders that might influence hormonal metabolism, they write.

Deficiencies in one or more of the hormones, defined as a level no higher than the 10th percentile observed among similarly aged men in the reference cohort, were common among the men with HF. Significant inverse correlations were observed between NYHA functional class, independent of HF etiology and levels of TT, eFT, and DHEAS. Alone among the four measurements, DHEAS levels were directly correlated with LVEF and inversely correlated with plasma levels of N-terminal pro-brain natriuretic factor (NT-proBNP), a marker of HF severity.

Reductions in all four measures of anabolic hormone status were associated with a significantly increased risk of death over an average follow-up of 930 days after adjustment for age, NYHA class, LVEF, NT-proBNP levels, kidney function, hemoglobin, and diabetes. The mortality hazard ratio dropped by 6% for every 10-pg/mL increase in eFT (p=0.01) and by 16% per 1-ng/mL TT, 7% per 100-ng/mL DHEAS, and 5% per 10-ng/mL IGF-1. Mortality increased significantly with the number of hormone deficiencies.

"The real challenge is whether these are just markers for the disease state vs potential targets for therapy," according to Fonarow. Even if they ultimately prove to be independently prognostic, he said, accepting them as a routine part of HF risk assessments would require that they provide clinically meaningful information beyond what is available from traditional risk-assessment tools. And for now, Fonarow said, "We really don't have any compelling data that replacement therapy, whether with growth hormone, testosterone, or otherwise, is going to have a favorable effect on functional status, much less clinical outcome, in these patients."