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

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.

Keywords: Cardiovascular; Endothelial function.

Figure 1

Endothelial dysfunction describes multiple phenotypic states. Left panel: In homeostatic conditions, the healthy endothelium regulates the physiological vascular function and structure through multiple beneficial effects of nitric oxide (NO), hydrogen sulphide (H₂S), and carbon monoxide (CO), as detailed in the text. Right panel: Dysfunctional endothelium is characterized by decreased production of NO and chronic increase of reactive oxygen species (ROS) able to overwhelm the intra-cellular antioxidant defence leading to onset and progression of atherosclerosis. AA, amino acids; EndMT, endothelial–mesenchymal transition; eNOS, endothelial nitric oxide synthase.

Figure 2

Schematic representation of the endothelial factors underlying cardiovascular risk. ECFCs, endothelial colony-forming cells; EMVs, endothelial micro-vesicles; EndMT, endothelial–mesenchymal transition; FMD, flow-mediated dilatation; HSPG, heparan sulphate proteoglycans; IL, interleukin; MØ, macrophage; MR-proADM, mid-regional pro-adrenomedullin; NO, nitric oxide; oxLDL, oxidized low-density lipoprotein; ROS, reactive oxygen species; TGFβ, transforming growth factor beta.