Serially measured high-sensitivity cardiac troponin T, N-terminal-pro-B-type natriuretic peptide, high-sensitivity C-reactive protein, and growth differentiation factor 15 for risk assessment after acute coronary syndrome: the BIOMArCS cohort

Author:

Gürgöze Muhammed T1ORCID,Akkerhuis K Martijn1,Oemrawsingh Rohit M2,Umans Victor A W M3,Kietselaer Bas45,Schotborgh Carl E6,Ronner Eelko7,Lenderink Timo4ORCID,Aksoy Ismail8,van der Harst Pim910,Asselbergs Folkert W1112,Maas Arthur C13,Oude Ophuis Anton J14,Krenning Boudewijn115,de Winter Robbert J11,The Salem H K16,Wardeh Alexander J17,Hermans Walter R M18,Cramer G Etienne19,van Gorp Ina1,de Rijke Yolanda B1,van Schaik Ron H N1,Boersma Eric1ORCID

Affiliation:

1. Erasmus MC, University Medical Centre Rotterdam , Dr. Molewaterplein 40, 3015 GD, Rotterdam , the Netherlands

2. Department of Cardiology, Albert Schweitzer Hospital , Albert Schweitzerplaats 25, 3318 AT, Dordrecht , the Netherlands

3. Department of Cardiology, Northwest Clinics , Wilhelminalaan 12, 1815 JD, Alkmaar , the Netherlands

4. Department of Cardiology, Zuyderland Hospital , Henri Dunantstraat 5, 6419 PC, Heerlen , the Netherlands

5. Department of Cardiovascular Medicine, Mayo Clinic , 201-299 2nd Ave SW, Rochester, MN 55902 , USA

6. Department of Cardiology, HagaZiekenhuis , Leyweg 275, 2545 CH, Den Haag , the Netherlands

7. Department of Cardiology, Reinier de Graafweg 5 , 2625 AD, Delft , the Netherlands

8. Department of Cardiology, Admiraal de Ruyter Hospital , ‘s- Gravenpolderseweg 114, 4462 RA, Goes , the Netherlands

9. Department of Cardiology, University Medical Centre Groningen , Hanzeplein 1, 9713 GZ, Groningen , the Netherlands

10. Department of Cardiology, University Medical Centre Utrecht , Heidelberglaan 100, 3584 CX, Utrecht , the Netherlands

11. Department of Cardiology, Amsterdam University Medical Centres, Amsterdam University Medical Centres, University of Amsterdam , Meibergdreef 9, 1105 AZ, Amsterdam , the Netherlands

12. Health Data Research UK and Institute of Health Informatics, University College London , Gibbs Building, 215 Euston Rd., London, NW1 2BE , UK

13. Department of Cardiology, Gelre Hospital , Den Elterweg 77, 7207 AE, Zutphen , the Netherlands

14. Department of Cardiology, Canisius-Wilhelmina Hospital , Weg door Jonkerbos 100, 6532 SZ, Nijmegen , the Netherlands

15. Department of Cardiology, Franciscus Gasthuis & Vlietland , Kleiweg 500, 3045 PM, Rotterdam , the Netherlands

16. Department of Cardiology, Treant Zorggroep , Dr. G.H. Amshoffweg 1, 7909 AA, Hoogeveen , the Netherlands

17. Department of Cardiology, Haaglanden Medical Centre , Lijnbaan 32 2512 VA, Den Haag , the Netherlands

18. Department of Cardiology, Elizabeth-Tweesteden Hospital , Doctor Deelenlaan 5, 5042 AD, Tilburg , the Netherlands

19. Department of Cardiology, Radboud University Medical Centre , Geert Grooteplein Zuid 10, 6525 GA, Nijmegen , the Netherlands

Abstract

Abstract Aims Evidence regarding the role of serial measurements of biomarkers for risk assessment in post-acute coronary syndrome (ACS) patients is limited. The aim was to explore the prognostic value of four, serially measured biomarkers in a large, real-world cohort of post-ACS patients. Methods and results BIOMArCS is a prospective, multi-centre, observational study in 844 post-ACS patients in whom 12 218 blood samples (median 17 per patient) were obtained during 1-year follow-up. The longitudinal patterns of high-sensitivity cardiac troponin T (hs-cTnT), N-terminal-pro-B-type natriuretic peptide (NT-proBNP), high-sensitivity C-reactive protein (hs-CRP), and growth differentiation factor 15 (GDF-15) were analysed in relation to the primary endpoint (PE) of cardiovascular mortality and recurrent ACS using multivariable joint models. Median age was 63 years, 78% were men and the PE was reached by 45 patients. The average biomarker levels were systematically higher in PE compared with PE-free patients. After adjustment for 6-month post-discharge Global Registry of Acute Coronary Events score, 1 standard deviation increase in log[hs-cTnT] was associated with a 61% increased risk of the PE [hazard ratio (HR) 1.61, 95% confidence interval (CI) 1.02–2.44, P = 0.045], while for log[GDF-15] this was 81% (HR 1.81, 95% CI 1.28–2.70, P = 0.001). These associations remained significant after multivariable adjustment, while NT-proBNP and hs-CRP were not. Furthermore, GDF-15 level showed an increasing trend prior to the PE (Structured Graphical Abstract). Conclusion Longitudinally measured hs-cTnT and GDF-15 concentrations provide prognostic value in the risk assessment of clinically stabilized patients post-ACS. Clinical Trial Registration The Netherlands Trial Register. Currently available at URL https://trialsearch.who.int/; Unique Identifiers: NTR1698 and NTR1106.

Funder

COBAS C

COBAS E

ELECSYS

Netherlands Heart Foundation

Netherlands Heart Institute-Interuniversity Cardiology Institute of Netherlands

Working Group of Cardiovascular Research Netherlands

Eli Lilly

Publisher

Oxford University Press (OUP)

Subject

Cardiology and Cardiovascular Medicine,Critical Care and Intensive Care Medicine,General Medicine

Reference38 articles.

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2. 2020 ESC guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation;Collet;Rev Esp Cardiol (Engl Ed),2021

3. ESC guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation;Steg;Eur Heart J,2012

4. GRACE score among six risk scoring systems (CADILLAC, PAMI, TIMI, dynamic TIMI, zwolle) demonstrated the best predictive value for prediction of long-term mortality in patients with ST-elevation myocardial infarction;Littnerova;PLoS One,2015

5. Validation of the grace risk score to predict in-hospital and 6-month post-discharge mortality in patients with acute coronary syndrome;Neves;Int J Cardiovasc Sci,2021

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