Cardiovascular diseases are the first cause of mortality in Western countries and are estimated to cause 31% of all deaths worldwide (WHO statistics, January 2015). They have a major socio-economic impact given the near-epidemic spread of the metabolic syndrome (that combines obesity, hypertension, diabetes and dyslipidemia) which carries a high risk of cardiovascular morbidity. Vascular atherosclerosis is the underlying pathogenic process driven by these risk factors, and there is now a wide consensus that endothelial dysfunction is the early step leading to atherogenesis, with loss of the anti-thrombotic, anti-hypertrophic and vasorelaxing properties of the healthy endothelial cells. Endothelial dysfunction at its early stages is difficult to detect non-invasively. Therefore, a robust biomarker of endothelial dysfunction is in great need for the detection of early stages of atherosclerosis and would allow better prevention, as well as improved risk stratification of cardiovascular diseases.

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Such a biomarker currently does not exist. Despite the identification of several circulating candidate molecules, none of them has clinically proven its superiority or even usefulness to improve risk stratification beyond the simple detection of traditional cardiovascular risk factors.  This may be due to the fact that these candidate molecules, most of which are detected in the plasma, only reflect limited or unimportant aspects of the pathophysiologic process leading to endothelial dysfunction/atherogenesis, or circulate in very low concentrations (hampering their detection, with a low dynamic range), or are by-products of late destruction of the vascular wall, when disease has already fully developed.