Copeptin in patients with heart failure and preserved ejection fraction: a report from the prospective KaRen-study

Camilla Hage, Lars H Lund, Erwan Donal, Jean-Claude Daubert, Cecilia Linde, Linda Mellbin, Camilla Hage, Lars H Lund, Erwan Donal, Jean-Claude Daubert, Cecilia Linde, Linda Mellbin

Abstract

Introduction: Underlying mechanisms of heart failure (HF) with preserved ejection fraction (HFPEF) remain unknown. We explored copeptin, a biomarker of the arginine vasopressin system, hypothesising that copeptin in HFPEF is elevated, associated with diastolic dysfunction and N-terminal pro-brain natriuretic peptide (NT-proBNP) and predictive of HF hospitalisation and mortality.

Methods and analysis: In a prospective observational substudy of the The Karolinska Rennes (KaRen) 86 patients with symptoms of acute HF and ejection fraction (EF) ≥45% were enrolled. After 4-8 weeks, blood sampling and echocardiography was performed. Plasma-copeptin was analysed in 86 patients and 62 healthy controls. Patients were followed in median 579 days (quartile 1; quartile 3 (Q1;Q3) 276;1178) regarding the composite end point all-cause mortality or HF hospitalisation.

Ethics and dissemination: The patients with HFPEF had higher copeptin levels, median 13.56 pmol/L (Q1;Q3 8.56;20.55) than controls 5.98 pmol/L (4.15;9.42; p<0.001). Diastolic dysfunction, assessable in 75/86 patients, was present in 45 and absent in 30 patients. Copeptin did not differ regarding diastolic dysfunction and did not correlate with cardiac function but with NT-proBNP (r=0.223; p value=0.040). In univariate Cox regression analysis log copeptin predicted the composite end point (HR 1.56 (95% CI 1.03 to 2.38; p value=0.037)) but not after adjusting for NT-proBNP (HR 1.39 (95% CI 0.91 to 2.12; p value=0.125)).

Conclusions: In the present patients with HFPEF, copeptin is elevated, correlates with NT-proBNP but not markers of diastolic dysfunction, and has prognostic implications, however blunted after adjustment for NT-proBNP. The HFPEF pathophysiology may be better reflected by markers of neurohormonal activation than by diastolic dysfunction.

Trial registration number: ClinicalTrials.gov NCT00774709.

Keywords: HEART FAILURE.

Figures

Figure 1
Figure 1
Copeptin levels in KaRen patients divided according to diastolic dysfunction and in healthy controls presented as boxplots displaying IQR, median (-), mean (♦) and outliers (●). Whiskers represent maximum observation within 1.5 IQR above the 75th centile.
Figure 2
Figure 2
Correlation between copeptin and biochemical markers, echocardiographic variables and clinical variables in the 86 patients in KaRen biochemistry substudy.

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