Obesity‐related inflammatory protein signature in cardiovascular clinical outcomes: results from the Gutenberg Health Study

Author:

Panova‐Noeva Marina12ORCID,Koeck Thomas34,Schoelch Corinna5,Schulz Andreas3,Prochaska Jürgen H.234,Michal Matthias46,Strauch Konstantin7,Schuster Alexander K.8,Lackner Karl J.49,Münzel Thomas2410,Hennige Anita M.11,Wild Philipp S.23412

Affiliation:

1. Translational Medicine and Clinical Pharmacology Boehringer Ingelheim Pharma GmbH & Co. KG Ingelheim Germany

2. Center for Thrombosis and Haemostasis University Medical Center, Johannes Gutenberg University Mainz Mainz Germany

3. Preventive Cardiology and Preventive Medicine, Center for Cardiology University Medical Center, Johannes Gutenberg University Mainz Mainz Germany

4. German Centre for Cardiovascular Research (DZHK), Partner Site Rhine‐Main Mainz Germany

5. Translational Medicine and Clinical Pharmacology, Boehringer Ingelheim Pharma GmbH & Co. KG Biberach Germany

6. Department of Psychosomatic Medicine and Psychotherapy University Medical Center, Johannes Gutenberg University Mainz Mainz Germany

7. Institute for Medical Biometrics, Epidemiology and Informatics (IMBEI), University Medical Center Johannes Gutenberg University Mainz Mainz Germany

8. Department of Ophthalmology, University Medical Center Johannes Gutenberg University Mainz Mainz Germany

9. Institute of Clinical Chemistry and Laboratory Medicine, University Medical Center Johannes Gutenberg University Mainz Mainz Germany

10. Department of Cardiology‐Cardiology I, University Medical Center Johannes Gutenberg University Mainz Mainz Germany

11. Therapeutic Area CardioMetabolism & Respiratory, Boehringer Ingelheim International GmbH Biberach Germany

12. Institute of Molecular Biology (IMB) Mainz Germany

Abstract

AbstractObjectiveThe objective of this study was to investigate whether an obesity‐related inflammatory protein signature (OIPS) is associated with adverse cardiovascular events.MethodsThe Olink Target 96 Inflammation panel was performed in 6662 participants from the population‐based Gutenberg Health Study (GHS). The OIPS was selected by a logistic regression model, and its association with cardiovascular outcomes was evaluated by Cox regression analysis. The GHS‐derived OIPS was externally validated in the MyoVasc study.ResultsThe identified OIPS entailed 21 proteins involved in chemokine activity, tumor necrosis factor (TNF) receptor binding, and growth factor receptor binding. The signature revealed a novel positive association of axis inhibition protein 1 with obesity. The OIPS was associated with increased risk of all‐cause and cardiac deaths, major adverse cardiovascular events, and incident coronary artery disease, independent of clinical covariates and established risk instruments. A BMI‐stratified analysis confirmed the association of OIPS with increased death in those with obesity and overweight and with increased risk for coronary artery disease in those with obesity. The association of OIPS with increased risk of all‐cause and cardiac deaths was validated in the MyoVasc cohort.ConclusionsThe OIPS showed a significant association with adverse clinical outcomes, particularly in those with overweight and obesity, and represents a promising tool for identifying patients at higher risk for worse cardiovascular outcomes.

Funder

Stiftung Rheinland-Pfalz für Innovation

Boehringer Ingelheim

Philips Medical Systems

Deutsches Zentrum für Herz-Kreislaufforschung

Publisher

Wiley

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