Prognostic biomarker soluble ST2 exhibits diurnal variation in chronic heart failure patients
Crnko, Sandra; Printezi, Markella I; Jansen, Tijn P J; Leiteris, Laurynas; van der Meer, Manon G; Schutte, Hilde; van Faassen, Martijn; du Pré, Bastiaan C; de Jonge, Nicolaas; Asselbergs, Folkert W; Gaillard, Carlo A J M; Kemperman, Hans; Doevendans, Pieter A; Sluijter, Joost P G; van Laake, Linda W
(2020) ESC heart failure, volume 7, issue 3, pp. 1224 - 1233
(Article)
Abstract
AIM: Soluble suppression of tumorigenicity-2 (sST2) is a strong prognostic biomarker in heart failure. The emerging understanding of circadian biology in cardiovascular disease may lead to novel applications in prognosis and diagnosis and may provide insight into mechanistic aspects of the disease-biomarker interaction. So far, it is unknown whether sST2
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exhibits a diurnal rhythm. Repeated measurements of sST2 may aid in clinical decision making. The goal of this study was to investigate whether sST2 exhibits diurnal variation in patients with heart failure with reduced ejection fraction (HFrEF) and in control subjects, thereby enhancing its diagnostic and prognostic values. METHODS AND RESULTS: The study comprised 32 subjects: 16 HFrEF patients and 16 controls. Blood was collected at seven subsequent time points during a 24 h time period. sST2, N-terminal pro-B-type natriuretic peptide (NT-proBNP), melatonin, and cortisol were measured from serum. Peak values of sST2 clustered at daytime (modal value: 5 p.m.) in 87.6% of all subjects (81.3% of patients, P = 0.021; 93.8% of controls, P = 0.001), and minimum concentrations at night-time (modal value: 5 a.m.) in 84.4% (87.5% of patients, P = 0.004 81.3% of controls, P = 0.021). A cosinor analysis of mean normalized sST2 values revealed significant cosine shaped 24 h oscillations of patients (P = 0.026) and controls (P = 0.037). NT-proBNP in contrast did not show a diurnal rhythm, while melatonin and cortisol patterns were intact in all subjects. CONCLUSIONS: sST2 exhibits a diurnal rhythm with lower values in the morning than in the late afternoon. This new insight could lead to refinement of its diagnostic and prognostic values through specified and consistent sampling times with repeated measurements. For example, by measuring sST2 during the afternoon, when levels are at their highest, false negatives on prognosis prediction could be avoided.
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Keywords: Biomarker, Circadian rhythm, Diurnal rhythm, Heart failure, NT-proBNP, sST2, Cardiology and Cardiovascular Medicine, Journal Article
ISSN: 2055-5822
Publisher: The Heart Failure Association of the European Society of Cardiology
Note: Funding Information: S.C., M.P., T.J., L.L., M.M., H.S., M.F., B.P., N.J., C.G., H.K., P.D., and J.S. have no conflict of interest. F.A. was supported by UCL Hospitals NIHR Biomedical Research Centre. L.L. received (related to the current work) NT‐proBNP assays from Roche and ST2 assays from Sopachem BV, in a form of an investigator‐initiated study, and (outside) consultancy fees from Abbott, Vifor, Novartis, and Medtronic, to the UMCU. Funding Information: This work was supported by the Netherlands Heart Foundation Dekker Grant (2013T056 to LL), Jacob Jongbloed Talent Society Grant (Circulatory Health, UMCU; to S.C.) and by Horizon2020 ERC‐2016‐COG EVICARE (725229 to J.P.G.S.). The authors acknowledge the support from Innovation and the Netherlands CardioVascular Research Initiative (CVON): The Dutch Heart Foundation; Dutch Federation of University Medical Centres; the Netherlands Organization for Health Research and Development (ZonMw); and the Royal Netherlands Academy of Arts and Sciences (Koninklijke Nederlandse Akademie van Wetenschappen). Funding Information: This work was supported by the Netherlands Heart Foundation Dekker Grant (2013T056 to LL), Jacob Jongbloed Talent Society Grant (Circulatory Health, UMCU; to S.C.) and by Horizon2020 ERC-2016-COG EVICARE (725229 to J.P.G.S.). The authors acknowledge the support from Innovation and the Netherlands CardioVascular Research Initiative (CVON): The Dutch Heart Foundation; Dutch Federation of University Medical Centres; the Netherlands Organization for Health Research and Development (ZonMw); and the Royal Netherlands Academy of Arts and Sciences (Koninklijke Nederlandse Akademie van Wetenschappen). The authors would like to thank Walid al Hedni for performing proBNP analysis, Lilian Homsma for organizing clinical data, Leanne Smit and Loes Peters for their help with processing blood samples, and Lena Bosch for helping with patient inclusions. Publisher Copyright: © 2020 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology
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