Endothelial function in cardiovascular medicine: a consensus paper of the European Society of Cardiology Working Groups on Atherosclerosis and Vascular Biology, Aorta and Peripheral Vascular Diseases, Coronary Pathophysiology and Microcirculation, and Thrombosis

Author:

Alexander Yvonne1,Osto Elena23ORCID,Schmidt-Trucksäss Arno4ORCID,Shechter Michael56,Trifunovic Danijela7ORCID,Duncker Dirk J8ORCID,Aboyans Victor9,Bäck Magnus1011,Badimon Lina12ORCID,Cosentino Francesco13ORCID,De Carlo Marco14,Dorobantu Maria15ORCID,Harrison David G16,Guzik Tomasz J1718,Hoefer Imo19ORCID,Morris Paul D2021ORCID,Norata Giuseppe D22,Suades Rosa13ORCID,Taddei Stefano23,Vilahur Gemma12,Waltenberger Johannes2425,Weber Christian26272829ORCID,Wilkinson Fiona1,Bochaton-Piallat Marie-Luce30ORCID,Evans Paul C2021ORCID

Affiliation:

1. Centre for Bioscience, Faculty of Science & Engineering, Manchester Metropolitan University, Manchester, UK

2. Institute of Clinical Chemistry, University and University Hospital Zurich, University Heart Center, Zurich, Switzerland

3. Laboratory of Translational Nutrition Biology, Swiss Federal Institute of Technology, Zurich, Switzerland

4. Division of Sports and Exercise Medicine, Department of Sport, Exercise and Health, Medical Faculty, University of Basel, Basel, Switzerland

5. Leviev Heart Center, Chaim Sheba Medical Center, Tel Hashomer, Israel

6. Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

7. Cardiology Department, Clinical Centre of Serbia, Faculty of Medicine, University of Belgrade, Belgrade, Serbia

8. Division of Experimental Cardiology, Department of Cardiology, Thoraxcenter, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands

9. Department of Cardiology, Dupuytren University Hospital, Inserm U-1094, Limoges University, Limoges, France

10. Department of Cardiology, Center for Molecular Medicine, Karolinska University Hospital, Solna, Stockholm, Sweden

11. INSERM U1116, Université de Lorraine, Centre Hospitalier Régional Universitaire de Nancy, Vandoeuvre les Nancy, France

12. Cardiovascular Program-ICCC, IR-Hospital de la Santa Creu i Sant Pau, CiberCV, Autonomous University of Barcelona, Barcelona, Spain

13. Unit of Cardiology, Karolinska Institute and Karolinska University Hospital, Solna, Stockholm, Sweden

14. Catheterization Laboratory, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy

15. ‘CarolDavila’ University of Medicine and Pharmacy, Bucharest, Romania

16. Vanderbilt University School of Medicine, Nashville, TN, USA

17. Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK

18. Department of Medicine, Jagiellonian University Collegium Medicum, Cracow, Poland

19. Laboratory of Clinical Chemistry and Hematology, University Medical Centre Utrecht, The Netherlands

20. Department of Infection, Immunity and Cardiovascular Disease, Bateson Centre & INSIGNEO Institute, University of Sheffield, Sheffield S10 2RX, UK

21. Insigneo Institute for In Silico Medicine, Sheffield, UK

22. Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Milan, Italy

23. Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy

24. Department of Cardiovascular Medicine, Medical Faculty, University of Münster, Münster, Germany

25. SRH Central Hospital Suhl, Suhl, Germany

26. Institute for Cardiovascular Prevention (IPEK), Ludwig-Maximillian-Universität (LMU) München, Munich, Germany

27. German Center for Cardiovascular Research (DZHK), partner site Munich Heart Alliance, Munich, Germany

28. Munich Cluster for Systems Neurology (SyNergy), Munich, Germany

29. Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands

30. Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, Geneva, Switzerland

Abstract

Abstract Endothelial cells (ECs) are sentinels of cardiovascular health. Their function is reduced by the presence of cardiovascular risk factors, and is regained once pathological stimuli are removed. In this European Society for Cardiology Position Paper, we describe endothelial dysfunction as a spectrum of phenotypic states and advocate further studies to determine the role of EC subtypes in cardiovascular disease. We conclude that there is no single ideal method for measurement of endothelial function. Techniques to measure coronary epicardial and micro-vascular function are well established but they are invasive, time-consuming, and expensive. Flow-mediated dilatation (FMD) of the brachial arteries provides a non-invasive alternative but is technically challenging and requires extensive training and standardization. We, therefore, propose that a consensus methodology for FMD is universally adopted to minimize technical variation between studies, and that reference FMD values are established for different populations of healthy individuals and patient groups. Newer techniques to measure endothelial function that are relatively easy to perform, such as finger plethysmography and the retinal flicker test, have the potential for increased clinical use provided a consensus is achieved on the measurement protocol used. We recommend further clinical studies to establish reference values for these techniques and to assess their ability to improve cardiovascular risk stratification. We advocate future studies to determine whether integration of endothelial function measurements with patient-specific epigenetic data and other biomarkers can enhance the stratification of patients for differential diagnosis, disease progression, and responses to therapy.

Funder

Swedish Heart and Lung Foundation

Spanish Ministry of Economy, Competitiveness and Science

Carlos III Institute of Health

CIBERCV

Swiss National Science Foundation

Swedish Research Council

The Netherlands Cardiovascular Research Initiative

Dutch Heart Foundation

British Heart Foundation

Wellcome Trust Clinical Research Career Development Fellowship

National Institutes of Health

Fondazione Cariplo

Italian Ministry of Education, University and Research

European Foundation for the Study of Diabetes

EFSD

Fondazione Telethon

Swiss National Science Foundation Prima and Sinergia

Swiss Card-Onco-Grant—Alfred

Hartmann Müller—Foundation and Jubilaeumsstiftung von SwissLife

European Society of Cardiology Research

Spanish Ministry of Science and Innovation

FEDER ‘Una Manera de Hacer Europa’

Deutsche Forschungsgemeinschaft

DFG

Excellence Cluster SyNergy

European Research Council

Publisher

Oxford University Press (OUP)

Subject

Physiology (medical),Cardiology and Cardiovascular Medicine,Physiology

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