Vienna, Austria - Plasma levels of copeptin, the C-terminal peptide fragment of a precursor to the antidiuretic and vasoconstricting hormone vasopressin, can predict long-term mortality in patients with almost any degree of chronic heart failure, and as a prognostic biomarker it appears to be in the same league as the natriuretic peptides, according to an observational study [1].

The findings, its authors say, have implications for the possible use of agents that block the renal vasopressin (V₂) receptor in the treatment of acute decompensated heart failure (ADHF). The group had previously shown copeptin to be strong prognosticator in that setting [2]; the peptide has also been prognostic in acute MI [3].

The new study, which followed 786 patients with chronic heart failure ranging from NYHA class 1 to class 4, appears in the July 22, 2008 issue of Journal of the American College of Cardiology and was published online July 14.

"Our current data confirm that increased levels of copeptin are linked to excess mortality, and this link is maintained irrespective of the clinical signs of severity of the disease," write the authors, led by Dr Stephanie Neuhold (Medical University of Vienna, Austria).

Speculating, they add, "Copeptin could therefore emerge as an independent marker to identify heart-failure patients from the whole spectrum of the disease who could benefit from adjunct therapy with a V₂ antagonist. This could in the future permit a more tailored therapy for heart-failure patients."

That idea should be explored in future studies, urge Neuhold et al. In the US, no vasopressin antagonists are currently approved or have garnered formal FDA-advisory-panel support for either chronic or acute heart failure. The oral V₂-receptor selective antagonist tolvaptan (Otsuka America Pharmaceuticals), as covered by heartwire, recently received such a panel recommendation for the indication of hypervolemic or euvolemic hyponatremia, regardless of etiology.

In the current study, NYHA class emerged as the most powerful risk predictor of mortality among those evaluated. Copeptin was the most predictive among patients with class 2 disease and those in class 3 (p=0.0001 for both groups); it was less predictive but still significant in class 4 heart failure (p=0.0181).

Other markers that were independently prognostic in that analysis included LVEF, age, systolic blood pressure, serum sodium, and glomerular filtration rate. Patients had been followed for an average of 16 months.

It's clinically important that copeptin was the most "compelling" as an independent mortality predictor in NYHA class 2 and 3, because those classes "are more difficult to judge in the ambulatory setting than the more obvious NYHA functional classes 1 and 4," the group writes.

Copeptin was a stronger prognosticator than either brain natriuretic peptide (BNP) or N-terminal pro-BNP (NT-proBNP) in this analysis, and combining either natriuretic peptide with copeptin only slightly increased the predictive power of any marker on its own.

Neuhold et al call the natriuretic peptides "certainly the benchmark against which all novel biomarkers must be measured."

Although there are many data suggesting that levels of vasopressin itself are correlated with heart-failure severity, the hormone isn't well suited to use as a biomarker due to its instability in vitro, affinity for platelets, and rapid physiologic clearance, according to the group. In contrast, copeptin "is synthesized and secreted in equimolar amounts to vasopressin. Its advantages are its long stability and that it can be quickly and reliably measured in unprocessed plasma or serum."