Copeptin and Peroxiredoxin-4 Independently Predict Mortality in Patients With Nonspecific Complaints Presenting to the Emergency Department

Abstract

Patients presenting to emergency departments (ED) with nonspecific complaints (NSCs) such as "not feeling well,""feeling weak,""being tired,""general deterioration," or other similar chief complaints that do not have a readily identifiable probable etiology are a common patient group at risk for adverse outcomes. Certain biomarkers, which have not yet been tested for prognostic value when applied to ED patients with NSCs, have emerged as useful tools for predicting prognosis in patients with a variety of diseases. This study tested the hypothesis that two of these novel markers, copeptin (a C-terminal portion of provasopressin) and/or peroxiredoxin-4 (Prx4), an enzyme that degrades hydrogen peroxide, singly or together are helpful in predicting death in the near term among patients presenting to the ED with NSCs. The Basel Non-specific Complaints (BANC) study is a delayed type cross-sectional diagnostic study with a prospective 30-day follow-up. ED patients with NSCs were consecutively enrolled. Patients with vital parameters out of the normal range were excluded. The primary endpoint of this study was the predictive value of copeptin and Prx4 for 30-day mortality in patients with NSCs. Measurement of both copeptin and Prx4 was performed in serum samples with sandwich immunoluminometric assays. On follow-up at 30 days after ED presentation, 28 of 438 patients with NSC had died. Copeptin and Prx4 concentrations were significantly higher in nonsurvivors than in survivors (Kruskal-Wallis test, p = 0.0001 and p < 0.0001, respectively). In univariate models, Prx4 (likelihood ratio [LR] χ(2) = 22.24, p < 0.00001, concordance index [C-index] = 0.749) and copeptin (LR χ(2) = 16.98, p = 0.00004, C-index = 0.724) were both predictive of 30-day mortality, and elevated levels were associated with an increased mortality. The bivariable model, which included both Prx4 and copeptin (LR χ(2) = 28.22, p < 0.00001, C-index = 0.783), allows a significantly better prediction than the univariate Prx4 (p = 0.00025) and copeptin models (p = 0.00099), respectively. Both biomarkers provided independent and additional information to clinical risk scores (Katz Activities of Daily Living [ADL] and Charlson Comorbidity Index [CCI], all p < 0.0005). Copeptin and Prx4 are new prognostic markers in patients presenting to the ED with NSCs. Copeptin and Prx4 might be valuable tools for risk stratification and decision-making in this patient group.