Combining National Early Warning Score With Soluble Urokinase Plasminogen Activator Receptor (suPAR) Improves Risk Prediction in Acute Medical Patients: A Registry-Based Cohort Study

Objectives: Soluble urokinase plasminogen activator receptor is a prognostic biomarker associated with critical illness, disease progression, and risk of mortality. We aimed to evaluate whether soluble urokinase plasminogen activator receptor adds prognostic value to a vital sign-based score for clinical monitoring of patient risk (National Early Warning Score) in acute medical patients. Design: Registry-based observational cohort study of consecutively admitted acute medical patients. Setting: The Acute Medical Unit, Copenhagen University Hospital Amager and Hvidovre, Hvidovre, Denmark. Patients: Acute medical patients admitted between November 18, 2013, and September 30, 2015. Interventions: None. Measurements and Main Results: Of 17,312 included patients, admission National Early Warning Score was available for 16,244 (93.8%). During follow-up, 587 patients (3.4%) died in-hospital, 859 (5.0%) within 30 days, and 1,367 (7.9%) within 90 days. High soluble urokinase plasminogen activator receptor was significantly associated with in-hospital-, 30-day-, and 90-day mortality within all National Early Warning Score groups, in particular in patients with a low National Early Warning Score; for 30-day mortality, mortality rate ratios ranged from 3.45 (95% CI, 2.91–4.10) for patients with National Early Warning Score 0–1, to 1.86 (95% CI, 1.47–2.34) for patients with National Early Warning Score greater than or equal to 9 for every doubling in soluble urokinase plasminogen activator receptor (log2-transformed). Combining National Early Warning Score, age, and sex with soluble urokinase plasminogen activator receptor improved prediction of in-hospital-, 30-day-, and 90-day mortality, increasing the area under the curve (95% CI) for 30-day mortality from 0.86 (0.85–0.87) to 0.90 (0.89–0.91), p value of less than 0.0001, with a negative predictive value of 99.0%. Conclusions: The addition of soluble urokinase plasminogen activator receptor to National Early Warning Score significantly improved risk prediction of both low- and high-risk acute medical patients. Patients with low National Early Warning Score but elevated soluble urokinase plasminogen activator receptor had mortality risks comparable to that of patients with higher National Early Warning Score. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. The study was performed at the Copenhagen University Hospital Amager and Hvidovre, Hvidovre, Denmark. The funder had no role in the design of the study and collection, analysis, and interpretation of data and in writing the article. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (https://ift.tt/29S62lw). Drs. Rasmussen and Haupt have received funding for travel from ViroGates A/S, Denmark, the company that produces the suPARnostic assays; she is supported by a grant from the Lundbeck Foundation (grant number R180-2014–3360). Mr. Ladelund received funding from Novo Nordisk. Dr. Eugen-Olsen is a co-founder, shareholder, and Chief Scientific Officer (currently) of ViroGates A/S. Drs. Eugen-Olsen and Andersen are named inventors on patents on soluble urokinase plasminogen activator receptor as a prognostic biomarker; the patents are owned by Copenhagen University Hospital Amager and Hvidovre, Denmark, and licensed to ViroGates A/S. Dr. Ellekilde disclosed that she does not have any potential conflicts of interest. For information regarding this article, E-mail: line.jee.hartmann.rasmussen@regionh.dk Copyright © by 2018 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

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