Comment on consensus paper: Endothelial Function in Cardiovascular Precision Medicine

There is a wealth of evidence that endothelial dysfunction (ED) is a key player in the initiation of atherosclerosis and plaque progression. ED in coronary macro- or micro-vascular compartments may predict and/or drive disease progression into culprit lesions, acute coronary syndromes, and Ischemia and No-Obstructive-Coronary-Artery disease. Consistent with this notion, ED has been demonstrated in asymptomatic individuals with risk factors for atherosclerosis (i.e. before clinical manifestation of the diseases) and large clinical trials demonstrated that micro-vascular ED can independently predict major adverse cardiovascular events in populations at risk for coronary artery disease. However, there are several examples in the literature where the correlation between ED and disease risk varies considerably between studies. This can be partly attributed to technical considerations, thereby underlying the importance of methodological consistency, but may also be related to biological factors that vary between individuals and/or between populations therefore requiring a precision medicine approach

The aim of this position paper by the Working Group on Atherosclerosis and Vascular Biology and other Working Groups of the European Society of Cardiology was to present a brief overview of the recent developments in the Endothelial Function focusing on its role in in Cardiovascular Precision Medicine.

The Consensus statements are:

1. ED does not describe a single endothelial phenotype, but is characterized by a spectrum of phenotypic states, exemplified by multiple endothelial cells (EC) subsets and plasticity in atherosclerosis. The vascular biology community should delineate the contribution of various EC dysfunctional states to cardiovascular disease and develop new technologies to measure pathogenic EC subsets in the clinic.
   
   
2. Flow Mediated Dilatation (FMD) of the brachial arteries, the most commonly used measure of ED, predicted cardiovascular risk in some large clinical trials, but not others. Thus, we  recommend that a consensus, semi-automated methodology is adopted in future studies to minimize technical variation, and that reference FMD values are established for different populations.
   
   
3. Newer techniques to measure ED 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. In addition, larger clinical studies are needed to establish reference values and to assess their clinical utility.
   
   
4. Future work should determine whether the prognostic value of endothelial function measurement can be enhanced by integration with patient-specific information from omics and epigenetic studies and/or from analysis of patient-derived endothelial micro-vesicles and colony-forming cells.