TY - JOUR
T1 - Diurnal Variations in Natriuretic Peptide Levels
T2 - Clinical Implications for the Diagnosis of Acute Heart Failure
AU - Breidthardt, Tobias
AU - van Doorn, William P T M
AU - van der Linden, Noreen
AU - Diebold, Matthias
AU - Wussler, Desiree
AU - Danier, Isabelle
AU - Zimmermann, Tobias
AU - Shrestha, Samyut
AU - Kozhuharov, Nikola
AU - Belkin, Maria
AU - Porta, Caroline
AU - Strebel, Ivo
AU - Michou, Eleni
AU - Gualandro, Danielle M
AU - Nowak, Albina
AU - Meex, S J R
AU - Mueller, Christian
N1 - Funding Information:
This study was supported by research grants from the European Union, the Swiss National Science Foundation, the Swiss Heart Foundation, the Cardiovascular Research Foundation Basel, the University of Basel, the University Hospital Basel, Critical Diagnostics, Abbott, Alere, BRAHMS, Roche, and Singulex. The sponsors had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript.
Funding Information:
Dr Breidthardt received research grants from the Swiss National Science Foundation (PASMP3-134362), University Hospital Basel, Abbott, and Roche, as well as speaker or advisory fees from AstraZeneca, Daiichi Sankyo, Roche, and Vifor. These payments were made directly to University Hospital Basel, and no personal payments were received. Dr Kozhuharov received research grants from the Swiss National Science Foundation (P400PM-194477), Gottfried und Julia Bangerter-Rhyner-Stiftung, and the European Society of Cardiology. Dr Mueller received research grants from the Swiss National Science Foundation and the Swiss Heart Foundation, the European Union, the Cardiovascular Research Foundation Basel, the University of Basel, 8sense, Abbott, Alere, Astra Zeneca, Beckman Coulter, Biomerieux, BRAHMS, Critical Diagnostics, Nanosphere, Roche, Siemens, Singulex, and University Hospital Basel, as well as speaker or consulting honoraria from Abbott, Alere, AstraZeneca, BG Medicine, Biomerieux, Bristol Myers Squibb, Boehringer Ingelheim, BRAHMS, Cardiorentis, Daiichi Sankyo, Novartis, Roche, Sanofi, Singulex, and Siemens. Dr Meex received research funding and lecture fees from Abbott Laboratories and Roche Diagnostics. The other authors report no conflicts.
Publisher Copyright:
© 2022 Lippincott Williams and Wilkins. All rights reserved.
PY - 2022/6
Y1 - 2022/6
N2 - BACKGROUND: Current guidelines recommend interpreting concentrations of NPs (natriuretic peptides) irrespective of the time of presentation to the emergency department. We hypothesized that diurnal variations in NP concentration may affect their diagnostic accuracy for acute heart failure.METHODS: In a secondary analysis of a multicenter diagnostic study enrolling patients presenting with acute dyspnea to the emergency department and using central adjudication of the final diagnosis by 2 independent cardiologists, the diagnostic accuracy for acute heart failure of BNP (B-type NP), NT-proBNP (N-terminal pro-B-type NP), and MR-proANP (midregional pro-atrial NP) was compared among 1577 daytime presenters versus 908 evening/nighttime presenters. In a validation study, the presence of a diurnal rhythm in BNP and NT-proBNP concentrations was examined by hourly measurements in 44 stable individuals.RESULTS: Among patients adjudicated to have acute heart failure, BNP, NT-proBNP, and MR-proANP concentrations were comparable among daytime versus evening/nighttime presenters (all P=nonsignificant). Contrastingly, among patients adjudicated to have other causes of dyspnea, evening/nighttime presenters had lower BNP (median, 44 [18-110] versus 74 [27-168] ng/L; P<0.01) and NT-proBNP (median, 212 [72-581] versus 297 [102-902] ng/L; P<0.01) concentrations versus daytime presenters. This resulted in higher diagnostic accuracy as quantified by the area under the curve of BNP and NT-proBNP among evening/nighttime presenters (0.97 [95% CI, 0.95-0.98] and 0.95 [95% CI, 0.93-0.96] versus 0.94 [95% CI, 0.92-0.95] and 0.91 [95% CI, 0.90-0.93]) among daytime presenters (both P<0.01). These differences were not observed for MR-proANP. Diurnal variation of BNP and NT-proBNP with lower evening/nighttime concentration was confirmed in 44 stable individuals (P<0.01).CONCLUSIONS: BNP and NT-proBNP, but not MR-proANP, exhibit a diurnal rhythm that results in even higher diagnostic accuracy among evening/nighttime presenters versus daytime presenters.REGISTRATION: URL: https://www.CLINICALTRIALS: gov; Unique identifiers: NCT01831115, NCT02091427, and NCT02210897.
AB - BACKGROUND: Current guidelines recommend interpreting concentrations of NPs (natriuretic peptides) irrespective of the time of presentation to the emergency department. We hypothesized that diurnal variations in NP concentration may affect their diagnostic accuracy for acute heart failure.METHODS: In a secondary analysis of a multicenter diagnostic study enrolling patients presenting with acute dyspnea to the emergency department and using central adjudication of the final diagnosis by 2 independent cardiologists, the diagnostic accuracy for acute heart failure of BNP (B-type NP), NT-proBNP (N-terminal pro-B-type NP), and MR-proANP (midregional pro-atrial NP) was compared among 1577 daytime presenters versus 908 evening/nighttime presenters. In a validation study, the presence of a diurnal rhythm in BNP and NT-proBNP concentrations was examined by hourly measurements in 44 stable individuals.RESULTS: Among patients adjudicated to have acute heart failure, BNP, NT-proBNP, and MR-proANP concentrations were comparable among daytime versus evening/nighttime presenters (all P=nonsignificant). Contrastingly, among patients adjudicated to have other causes of dyspnea, evening/nighttime presenters had lower BNP (median, 44 [18-110] versus 74 [27-168] ng/L; P<0.01) and NT-proBNP (median, 212 [72-581] versus 297 [102-902] ng/L; P<0.01) concentrations versus daytime presenters. This resulted in higher diagnostic accuracy as quantified by the area under the curve of BNP and NT-proBNP among evening/nighttime presenters (0.97 [95% CI, 0.95-0.98] and 0.95 [95% CI, 0.93-0.96] versus 0.94 [95% CI, 0.92-0.95] and 0.91 [95% CI, 0.90-0.93]) among daytime presenters (both P<0.01). These differences were not observed for MR-proANP. Diurnal variation of BNP and NT-proBNP with lower evening/nighttime concentration was confirmed in 44 stable individuals (P<0.01).CONCLUSIONS: BNP and NT-proBNP, but not MR-proANP, exhibit a diurnal rhythm that results in even higher diagnostic accuracy among evening/nighttime presenters versus daytime presenters.REGISTRATION: URL: https://www.CLINICALTRIALS: gov; Unique identifiers: NCT01831115, NCT02091427, and NCT02210897.
KW - ASSOCIATION
KW - BLOOD-PRESSURE
KW - BNP
KW - CARDIOLOGY
KW - CREATININE
KW - DYSPNEA
KW - EMERGENCY-DEPARTMENT
KW - EUROPEAN-SOCIETY
KW - MANAGEMENT
KW - PLASMA
KW - circadian rhythm
KW - diagnostic techniques, cardiovascular
KW - dyspnea
KW - heart failure
KW - natriuretic peptides
U2 - 10.1161/circheartfailure.121.009165
DO - 10.1161/circheartfailure.121.009165
M3 - Article
C2 - 35670217
SN - 1941-3289
VL - 15
SP - E009165
JO - Circulation-Heart Failure
JF - Circulation-Heart Failure
IS - 6
M1 - 009165
ER -