Prognostic and diagnostic significance of copeptin in acute exacerbation of chronic obstructive pulmonary disease and acute heart failure: data from the ACE 2 study

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Abstract

Background

Copeptin is a novel biomarker that predicts mortality in lower respiratory tract infections and heart failure (HF), but the diagnostic value of copeptin in acute dyspnea and the prognostic significance of copeptin in acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is not clear.

Method

We determined copeptin and NT-proBNP concentrations at hospital admission in 314 patients with acute dyspnea who were categorized by diagnosis. Survival was registered after a median follow-up of 816 days, and the prognostic and diagnostic properties of copeptin and NT-proBNP were analyzed in acute HF ( n = 143) and AECOPD ( n = 84) separately.

Results

The median concentration of copeptin at admission was lower in AECOPD compared to acute HF (8.8 [5.2–19.7] vs. 22.2 [10.2–47.9]) pmol/L, p < 0.001), but NT-proBNP discriminated acute HF from non-HF related dyspnea more accurately than copeptin (ROC-AUC 0.85 [0.81–0.89] vs. 0.71 [0.66–0.77], p < 0.0001). Adjusted for basic risk factors, increased copeptin concentrations predicted mortality in AECOPD (HR per log (ln) unit 1.72 [95% CI 1.21–2.45], p = 0.003) and acute HF (1.61 [1.25–2.09], p < 0.001), whereas NT-proBNP concentrations predicted mortality only in acute HF (1.62 [1.27–2.06], p < 0.001). On top of a basic model copeptin reclassified a significant proportion of patients into a more accurate risk strata in AECOPD (NRI 0.60 [0.19–1.02], p = 0.004) and acute HF (0.39 [0.06–0.71], p = 0.020).

Conclusion

Copeptin is a strong prognostic marker in both AECOPD and acute HF, while NT-proBNP concentrations predict mortality only in patients with acute HF. NT-proBNP levels are superior to copeptin levels to diagnose acute HF in patients with acute dyspnea.

Electronic supplementary material

The online version of this article (10.1186/s12931-017-0665-z) contains supplementary material, which is available to authorized users.

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Most cited references 39

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The N-terminal Pro-BNP investigation of dyspnea in the emergency department (PRIDE) study.

James Januzzi, Carlos A Camargo, Saif Anwaruddin … (2005)

The utility of aminoterminal pro-brain natriuretic peptide (NT-proBNP) testing in the emergency department to rule out acute congestive heart failure (CHF) and the optimal cutpoints for this use are not established. We conducted a prospective study of 600 patients who presented in the emergency department with dyspnea. The clinical diagnosis of acute CHF was determined by study physicians who were blinded to NT-proBNP results. The primary end point was a comparison of NT-proBNP results with the clinical assessment of the managing physician for identifying acute CHF. The median NT-proBNP level among 209 patients (35%) who had acute CHF was 4,054 versus 131 pg/ml among 390 patients (65%) who did not (p 450 pg/ml for patients 900 pg/ml for patients >or=50 years of age were highly sensitive and specific for the diagnosis of acute CHF (p <0.001). An NT-proBNP level <300 pg/ml was optimal for ruling out acute CHF, with a negative predictive value of 99%. Increased NT-proBNP was the strongest independent predictor of a final diagnosis of acute CHF (odds ratio 44, 95% confidence interval 21.0 to 91.0, p <0.0001). NT-proBNP testing alone was superior to clinical judgment alone for diagnosing acute CHF (p = 0.006); NT-proBNP plus clinical judgment was superior to NT-proBNP or clinical judgment alone. NT-proBNP measurement is a valuable addition to standard clinical assessment for the identification and exclusion of acute CHF in the emergency department setting.

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Composite outcomes in randomized trials: greater precision but with greater uncertainty?

John Wood, Melanie Calvert, Carl Griffin … (2003)

Composite outcomes, in which multiple end points are combined, are frequently used as primary outcome measures in randomized trials and are often associated with increased statistical efficiency. However, such measures may prove challenging for the interpretation of results. In this article, we examine the use of composite outcomes in major clinical trials, assess the arguments for and against them, and provide guidance on their application and reporting. To assess incidence and quality of reporting, we systematically reviewed the use of composite end points in clinical trials in Annals of Internal Medicine, BMJ, Circulation, Clinical Infectious Diseases, Journal of the American College of Cardiology, JAMA, Lancet, New England Journal of Medicine, and Stroke from 1997 through 2001 using a sensitive search strategy. We selected for review 167 original reports of randomized trials (with a total of 300 276 patients) that included a composite primary outcome that incorporated all-cause mortality. Sixty-three trials (38%) were neutral both for the primary end point and the mortality component. Sixty trials (36%) reported significant results for the primary outcome measure but not for the mortality component. Only 6 trials (4%) were significant for the mortality component but not for the primary composite outcome, whereas 19 trials (11%) were significant for both. Twenty-two trials (13%) were inadequately reported. Our review suggests that reporting of composite outcomes is generally inadequate, implying that the results apply to the individual components of the composite outcome rather than only to the overall composite. Current guidelines for the undertaking and reporting of clinical trials could be revised to reflect the common use of composite outcomes in clinical trials.

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The prognostic value of B-type natriuretic peptide in patients with acute coronary syndromes.

Carolyn McCabe, J. Kelley Bentley, Marc Sabatine … (2001)

Brain (B-type) natriuretic peptide is a neurohormone synthesized predominantly in ventricular myocardium. Although the circulating level of this neurohormone has been shown to provide independent prognostic information in patients with transmural myocardial infarction, few data are available for patients with acute coronary syndromes in the absence of ST-segment elevation. We measured B-type natriuretic peptide in plasma specimens obtained a mean (+/-SD) of 40+/-20 hours after the onset of ischemic symptoms in 2525 patients from the Orbofiban in Patients with Unstable Coronary Syndromes-Thrombolysis in Myocardial Infarction 16 study. The base-line level of B-type natriuretic peptide was correlated with the risk of death, heart failure, and myocardial infarction at 30 days and 10 months. The unadjusted rate of death increased in a stepwise fashion among patients in increasing quartiles of base-line B-type natriuretic peptide levels (P< 0.001). This association remained significant in subgroups of patients who had myocardial infarction with ST-segment elevation (P=0.02), patients who had myocardial infarction without ST-segment elevation (P<0.001), and patients who had unstable angina (P<0.001). After adjustment for independent predictors of the long-term risk of death, the odds ratios for death at 10 months in the second, third, and fourth quartiles of B-type natriuretic peptide were 3.8 (95 percent confidence interval, 1.1 to 13.3), 4.0 (95 percent confidence interval, 1.2 to 13.7), and 5.8 (95 percent confidence interval, 1.7 to 19.7). The level of B-type natriuretic peptide was also associated with the risk of new or recurrent myocardial infarction (P=0.01) and new or worsening heart failure (P<0.001) at 10 months. A single measurement of B-type natriuretic peptide, obtained in the first few days after the onset of ischemic symptoms, provides powerful information for use in risk stratification across the spectrum of acute coronary syndromes. This finding suggests that cardiac neurohormonal activation may be a unifying feature among patients at high risk for death after acute coronary syndromes.

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Author and article information

Contributors

Jacob A. Winther: j.a.winther@medisin.uio.no

Journal

Journal ID (nlm-ta): Respir Res

Journal ID (iso-abbrev): Respir. Res

Title: Respiratory Research

Publisher: BioMed Central (London )

ISSN (Print): 1465-9921

ISSN (Electronic): 1465-993X

Publication date (Electronic): 3 November 2017

Publication date PMC-release: 3 November 2017

Publication date (Print): 2017

Volume: 18

Electronic Location Identifier: 184

Affiliations

[1 ]ISNI 0000 0000 9637 455X, GRID grid.411279.8, Division of Medicine, , Akershus University Hospital, ; Lørenskog, Norway

[2 ]Institute of Clinical Medicine, University of Oslo, Oslo, Norway

[3 ]ISNI 0000 0004 1936 8921, GRID grid.5510.1, Institute for Experimental Medical Research, Oslo University Hospital and University of Oslo, ; Oslo, Norway

[4 ]ISNI 0000 0000 9637 455X, GRID grid.411279.8, Division of Diagnostics and Technology, , Akershus University Hospital, ; Lørenskog, Norway

[5 ]ISNI 0000 0004 0389 8485, GRID grid.55325.34, Bioinformatics Core Facility, Institute for Medical Informatics, Oslo University Hospital and University of Oslo, ; Oslo, Norway

Article

Publisher ID: 665

DOI: 10.1186/s12931-017-0665-z

PMC ID: 5670515

PubMed ID: 29100503

SO-VID: f12b1dac-5d05-4639-8a1c-8b7a3d304a66

License:

Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

History

Date received : 29 May 2017

Date accepted : 11 October 2017

Funding

Funded by: Akershus University Hospital

Funded by: FundRef http://dx.doi.org/10.13039/501100005416, Norges Forskningsråd;

Custom metadata

ScienceOpen disciplines: Respiratory medicine

Keywords: copeptin,nt-probnp,copd,heart failure,epidemiology,dyspnea,hyponatremia,vasopressin,antidiuretic hormone

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ScienceOpen disciplines: Respiratory medicine

Keywords: copeptin, nt-probnp, copd, heart failure, epidemiology, dyspnea, hyponatremia, vasopressin, antidiuretic hormone

Prognostic and diagnostic significance of copeptin in acute exacerbation of chronic obstructive pulmonary disease and acute heart failure: data from the ACE 2 study

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Method

Results

Conclusion

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Related collections

Inflamed lung in vitro co-culture models

Most cited references 39

The N-terminal Pro-BNP investigation of dyspnea in the emergency department (PRIDE) study.

Composite outcomes in randomized trials: greater precision but with greater uncertainty?

The prognostic value of B-type natriuretic peptide in patients with acute coronary syndromes.

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