Increased 90-Day Mortality in Patients With Acute Heart Failure With Elevated Copeptin

Abstract

Background-In patients with heart failure (HF), increased arginine vasopressin concentrations are associated with more severe disease, making arginine vasopressin an attractive target for therapy. However, AVP is difficult to measure due to its in vitro instability and rapid clearance. Copeptin, the C-terminal segment of preprovasopressin, is a stable and reliable surrogate biomarker for serum arginine vasopressin concentrations. Methods and Results-The Biomarkers in Acute Heart Failure (BACH) trial was a 15-center, diagnostic and prognostic study of 1641 patients with acute dyspnea; 557 patients with acute HF were included in this analysis. Copeptin and other biomarker measurements were performed by a core laboratory at the University of Maryland. Patients were followed for up to 90 days after initial evaluation for the primary end point of all-cause mortality, HF-related readmissions, and HF-related emergency department visits. Patients with copeptin concentrations in the highest quartile had increased 90-day mortality (PϽ0.001; hazard ratio, 3.85). Mortality was significantly increased in patients with elevated copeptin and hyponatremia (PϽ0.001; hazard ratio, 7.36). Combined end points of mortality, readmissions, and emergency department visits were significantly increased in patients with elevated copeptin. There was no correlation between copeptin and sodium (rϭ0.047). Conclusions-This study showed significantly increased 90-day mortality, readmissions, and emergency department visits in patients with elevated copeptin, especially in those with hyponatremia. Copeptin was highly prognostic for 90-day adverse events in patients with acute HF, adding prognostic value to clinical predictors, ser um sodium, and natriuretic peptides. Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT00537628.(Circ Heart Fail. 2011;4:613-620.)

Differential Regulation of Plasma Copeptin Levels in Patients with Heart Failure: A Single-Center Prospective Study

“…Further, multiple regression analysis showed NT-proBNP as an independent predictor of plasma copeptin level. These findings lend further support to previous studies suggesting AVP and copeptin as neurohormonal markers for HF (Schrier and Abraham 1999;Neuhold et al 2008;Alehagen et al 2011;Maisel et al 2011), similar to BNP and NT-pro-BNP. Copeptin is simultaneously released with AVP from the neurohypophysis in response to osmotic as well as nonosmotic stimuli.…”

Randomised Assessment of Treatment using Panel Assay of Cardiac markers – Contemporary Biomarker Evaluation (RATPAC CBE)

“…In patients with established coronary artery disease, copeptin was not a strong predictor of cardiovascular outcome 168 and is probably a better predictor in patients with heart failure than in patients with chest pain. 267 Measurement of BNP has been proposed as an early diagnostic test for patients presenting with chest pain. 44 Although studies have shown an additive value of simultaneous measurement of BNP and cardiac troponin, [268][269][270] increased sensitivity is achieved at the expense of diagnostic specificity.…”

Prognostic performance of serial in‐hospital measurements of copeptin and multiple novel biomarkers among patients with worsening heart failure: results from the MOLITOR study

“…During hospitalization, natriuretic peptides are thought to be helpful in risk stratification,3, 4 and a fall in peptide levels correlate with a better prognosis 5, 6, 7, 8. Recently, other candidate peptides, such as mid‐regional pro‐adrenomedullin (MR‐proADM)2 and copeptin,9 were found to add prognostic value. Copeptin is C‐terminal fragment of pre‐pro‐vasopressin.…”