Association of Copeptin and N-Terminal proBNP Concentrations With Risk of Cardiovascular Death in Older Patients With Symptoms of Heart Failure

Study Questions:

What is the association between plasma concentrations of copeptin, combined with concentrations of the N-terminal fragment of the precursor to B-type natriuretic peptide (NT-proBNP), and mortality in a cohort of elderly patients with symptoms of heart failure?


The study was conducted in a primary health care population in Sweden enrolling 470 elderly patients with heart failure symptoms between January and December 1996. Clinical examination, echocardiography, and measurement of peptide concentrations were performed, with follow-up through December 2009. The primary outcome was all-cause mortality and cardiovascular mortality. To evaluate the possible prognostic value of adding biomarkers in a multivariate analysis, a weighted variable was produced based on the β value in the multivariate Cox proportional hazard regression analysis.


After a median follow-up of 13 years, there were 226 deaths from all causes, including 146 deaths from cardiovascular causes. Increased concentration of copeptin was associated with increased risk of all-cause mortality (fourth quartile vs. first quartile: 69.5% vs. 38.5%, respectively; hazard ratio [HR], 2.04; 95% confidence interval [CI], 1.38-3.02) and cardiovascular mortality (fourth quartile vs. first quartile: 46.6% vs. 26.5%; HR, 1.94; 95% CI, 1.20-3.13). The combination of elevated NT-proBNP concentrations and elevated copeptin concentrations also was associated with increased risk of all-cause mortality (copeptin fourth quartile: HR, 1.63; 95% CI, 1.08-2.47; p = 0.01; NT-proBNP fourth quartile: HR, 3.17; 95% CI, 2.02-4.98; p < 0.001). Using the two biomarkers simultaneously in the evaluation of cardiovascular mortality, there was a significant association for copeptin in the presence of NT-proBNP (log likelihood trend test, p = 0.048) and a significant association for NT-proBNP (fourth quartile: HR, 4.68; 95% CI, 2.63-8.34; p < 0.001).


The authors concluded that among elderly patients with symptoms of heart failure, elevated concentrations of copeptin and the combination of elevated concentrations of copeptin and NT-proBNP were associated with increased risk of all-cause mortality.


This study evaluated the use of two plasma biomarkers, one well known in the management of heart failure (NT-proBNP) and the other a new marker of pituitary vasopressin release (copeptin), during a follow-up time of 13 years. Even after a 13-year follow-up period, copeptin concentration possessed prognostic information concerning mortality risk, and both NT-proBNP and copeptin provided independent prognostic information. Vasopressin appears to play an important pathophysiological role in patients with heart failure, because increased release of vasopressin is associated with both increased preload and increased filling pressures as well as increased afterload, and the current study suggests that vasopressin may be a potential target for therapeutic intervention in heart failure.

Clinical Topics: Heart Failure and Cardiomyopathies, Noninvasive Imaging, Acute Heart Failure, Heart Failure and Cardiac Biomarkers, Echocardiography/Ultrasound

Keywords: Follow-Up Studies, Sweden, Biological Markers, Heart Failure, Echocardiography, Natriuretic Peptide, Brain

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