Abstract
Background: The arginine-vasopressin-aldosteron system is activated in patients with chronic heart failure and elevated serum concentrations of vasopressin as well as the c-terminal portion of its prohormone (copeptin) strongly predicts outcome of these patients. Re-absorption of urea by the kidneys is regulated by vasopressin and thereby it also influences blood urea nitrogen (BUN) concentrations. In the present study we investigated, whether the ratio of serum copeptin and BUN (copeptin-to-BUN) could be used to estimate long-term outcome of patients with chronic stable heart failure (CHF). Methods: We measured copeptin, BUN, high-sensitivity troponin T (hs-cTnT), plasma MR-proANP, MR-proADM and Nt-proBNP concentrations in 174 patients with CHF. Patients were followed for all-cause mortality and rehospitalization due to heart failure during a median time of 834days. Results: The ratio of copeptin-to-BUN was significantly higher among patients who died or were re-admitted to the hospital compared to those who remained event-free (0.86 vs. 0.45; p<0.001). In univariate Cox regression analysis, patients with copeptin-to-BUN ratio higher than the median had significantly higher risk of death or hospital re-admission than patients with lower copeptin-to-BUN ratio (HR 2.16 p<0.001; Figure). In multivariate analyses adjusted for several clinical variables and laboratory measures - including Nt-proBNP, MR-proADM, MR-proANP, hs-cTnT - the ratio of copeptin-to-BUN remained a highly significant determinant of long-term outcome (HR 1.645; p=0.023). Conclusion: In addition to well-established modern biomarkers, the copeptin-to-BUN ratio is a significant independent determinant of survival of patients with CHF. Future studies should evaluate whether copeptin-to-BUN ratio could be used to identify patients with advanced heart failure who might benefit from the use of vasopressin antagonists.
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