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. 2013 Nov 19;14(1):130.
doi: 10.1186/1465-9921-14-130.

Circulating levels of copeptin predict outcome in patients with pulmonary arterial hypertension

Nils P Nickel  1 , Ralf Lichtinghagen, Heiko Golpon, Karen M Olsson, Korbinian Brand, Tobias Welte, Marius M Hoeper
Affiliations

Circulating levels of copeptin predict outcome in patients with pulmonary arterial hypertension

Nils P Nickel et al. Respir Res. .

Abstract

Objective: To determine the levels of circulating copeptin in patients with pulmonary arterial hypertension (PAH), and to evaluate its relation with disease severity, outcome and response to treatment.

Background: Vasopressin is a key regulator of body fluid homeostasis. The co-secreted protein copeptin serves as surrogate for plasma vasopressin levels and increases in acute and chronic left ventricular dysfunction. Copeptin has not been studied in PAH.

Methods: Serum copeptin levels were evaluated in a retrospective cohort of 92 treatment-naïve patients with PAH, 39 patients with normal right ventricular hemodynamics (diseased controls) and 14 apparently healthy individuals (healthy controls). In a second prospective cohort of 15 patients with PAH, serial changes of copeptin levels after initiation of PAH treatment were measured. Copeptin levels were compared with clinical, biochemical and hemodynamic parameters as well as response to treatment and clinical outcome.

Results: Circulating copeptin levels were elevated in PAH patients compared to diseased controls (20.1 pmol/l vs. 5.1 pmol/l; p = 0.001). Baseline levels of copeptin correlated with NYHA functional class (r = 0.46; p = 0.01), 6 minute walking distance (r = -0.26; p = 0.04), NT-proBNP (r = 0.49, p = 0.01), creatinine (r = 0.39, p = 0.01) and estimated glomerular filtration rate (r = -0.32, p = 0.01). Copeptin levels did not correlate with hemodynamics but decreased after initiation of PAH therapy (p = 0.001). Elevated copeptin levels were associated with shorter survival (p < 0.001) and independent predictors of mortality in a multiple Cox regression analysis (HR1.4; 95% confidence interval 1.1-2.0; p = 0.02).

Conclusions: Patients with PAH had elevated copeptin levels. High circulating levels of copeptin were independent predictors of poor outcome, which makes copeptin a potentially useful biomarker in PAH.

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Figures

Figure 1
Figure 1
Copeptin levels in controls and patients with PAH from cohort 1 at baseline. Data are shown as median (IQR). Differences between the groups were assessed using Kruskal–Wallis one-way analysis of variance. * indicates p < 0.05.
Figure 2
Figure 2
Probability of survival according to baseline copeptin levels above or below the ROC derived cutoff of 13.2 pmol/l.
Figure 3
Figure 3
Probability of survival according to baseline NT-proBNP and copeptin levels above or below the ROC derived cutoffs.
See this image and copyright information in PMC

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