Plasma Copeptin Levels and Prediction of Outcome in Heart Failure Outpatients: Relation to Hyponatremia and Loop Diuretic Doses

Background: Copeptin, a stable fragment of the vasopressin prohormone, has been shown to be a significant biomarker for morbidity and mortality in heart failure. The aims of this study were to evaluate the influence of plasma sodium on the prognostic significance of copeptin concentrations in heart failure outpatients and to determine whether increased copeptin concentrations predict future development of hyponatremia. Methods and Results: A total of 340 heart failure patients with left ventricular systolic dysfunction were followed for 55 months (median) in a Danish heart failure clinic. A baseline measurement of plasma copeptin, N-terminal pro B-type natriuretic peptide (NT-proBNP), and sodium was performed, and the sodium concentrations were recorded during 3 months after the baseline visit in the heart failure clinic. Patients were divided into 3 groups according to copeptin tertiles. In multivariate Cox proportional hazard models adjusted for confounders, including plasma sodium, loop diuretic dose, and NT-proBNP, copeptin was a significant predictor of hospitalization or death (hazard ratio 1.4, 95% confidence interval 1.1-1.9; P < .019) but did not predict mortality independently from NT-proBNP. Additionally, copeptin concentrations did not predict future development of hyponatremia. Conclusions: Plasma copeptin levels predict mortality in outpatients with chronic heart failure independently from clinical variables, plasma sodium, and loop diuretic doses. Furthermore, copeptin predicts the combined end point of hospitalization or death independently from NT-proBNP. (J Cardiac Fail 2012:18:351-358)