Dipeptidyl peptidase 3 plasma levels predict cardiogenic shock and mortality in acute coronary syndromes

Author:

Wenzl Florian A1ORCID,Bruno Francesco23ORCID,Kraler Simon1ORCID,Klingenberg Roland45,Akhmedov Alexander1ORCID,Ministrini Stefano1ORCID,Santos Karine6ORCID,Godly Konstantin7,Godly Julia7,Niederseer David7ORCID,Manka Robert78,Bergmann Andreas6,Camici Giovanni G19ORCID,von Eckardstein Arnold10ORCID,Stähli Barbara7ORCID,Muller Olivier11ORCID,Roffi Marco12ORCID,Räber Lorenz13ORCID,Lüscher Thomas F131415ORCID

Affiliation:

1. Center for Molecular Cardiology, University of Zurich , Schlieren , Switzerland

2. Division of Cardiology, Cardiovascular and Thoracic Department, Molinette Hospital, Città della Salute e della Scienza , Turin , Italy

3. Royal Brompton and Harefield Hospitals , London , UK

4. Department of Cardiology, Kerckhoff Heart and Thorax Center, and Campus of the Justus Liebig University of Giessen , Giessen , Germany

5. DZHK (German Center for Cardiovascular Research), Partner Site Rhine-Main , Bad Nauheim , Germany

6. 4TEEN4 Pharmaceuticals GmbH , Hennigsdorf , Germany

7. Department of Cardiology, University Heart Center, University Hospital Zurich , Zurich , Switzerland

8. Institute of Diagnostic and Interventional Radiology, University Hospital Zurich, University of Zurich , Zurich , Switzerland

9. Department of Research and Education, University Hospital Zurich , Zurich , Switzerland

10. Institute of Clinical Chemistry, University Hospital Zurich and University of Zurich , Zurich , Switzerland

11. Service of Cardiology, Lausanne University Hospital , Lausanne , Switzerland

12. Department of Cardiology, Geneva University Hospital , Geneva , Switzerland

13. Department of Cardiology, Cardiovascular Center, University Hospital Bern , Bern , Switzerland

14. National Heart and Lung Institute, Imperial College , Guy Scadding Building, London , UK

15. School of Cardiovascular Medicine and Sciences, Kings College London , Strand, London , UK

Abstract

AbstractBackground and AimsDipeptidyl peptidase 3 (DPP3) is a protease involved in the degradation of angiotensin II which disturbs peripheral blood pressure regulation and compromises left ventricular function. This study examined the relationship of circulating DPP3 (cDPP3) with cardiogenic shock (CS) and mortality in patients presenting with acute coronary syndromes (ACS).MethodsPlasma cDPP3 levels were assessed at baseline and 12–24 h after presentation in patients with ACS prospectively enrolled into the multi-centre SPUM-ACS study (n = 4787).ResultsCirculating DPP3 levels were associated with in-hospital CS when accounting for established risk factors including the ORBI risk score [per log-2 increase, hazard ratio (HR) 1.38, 95% confidence interval (CI) 1.05–1.82, P = .021]. High cDPP3 was an independent predictor of mortality at 30 days (HR 1.87, 95% CI 1.36–2.58, P < .001) and at one year (HR 1.61, 95% CI 1.28–2.02, P < .001) after adjustment for established risk factors and the GRACE 2.0 score. Compared to values within the normal range, persistently elevated cDPP3 levels at 12–24 h were associated with 13.4-fold increased 30-day mortality risk (HR 13.42, 95% CI 4.86–37.09, P < .001) and 5.8-fold increased 1-year mortality risk (HR 5.79, 95% CI 2.70–12.42, P < .001). Results were consistent across various patient subgroups.ConclusionsThis study identifies cDPP3 as a novel marker of CS and increased mortality in patients with ACS. Circulating DPP3 offers prognostic information beyond established risk factors and improves early risk assessment.

Funder

Swiss National Science Foundation

AstraZeneca

Eli Lilly

Roche Diagnostics

Merck Sharpe and Dohme

Cardiovascular Research—Zurich Heart House

Lindenhof Foundation

Publisher

Oxford University Press (OUP)

Subject

Cardiology and Cardiovascular Medicine

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1. Artificial intelligence in cardiovascular medicine: clinical applications;European Heart Journal;2024-08-19

2. Cardiogenic shock: do we need a paradigm shift?;European Heart Journal;2024-07-10

3. DPP3 in Cardiogenic Shock;Clinical Chemistry;2024-05-29

4. Rising stars in cardiology: Florian A. Wenzl;European Heart Journal;2024-04-12

5. Safety and effectiveness of glycoprotein IIb/IIIa inhibitors in acute coronary syndromes: insights from the SPUM-ACS study;European Heart Journal - Cardiovascular Pharmacotherapy;2024-04-11

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