Testing Endothelial Function and its Clinical Relevance

Abstract

Endothelial dysfunction as an integrating index of the risk factor burden and genetic susceptibility is an early marker of atherothrombotic disease. Therefore, tremendous interest exists in its measurement and determination of the clinical utility of the evaluation of endothelial function.Different invasive and non-invasive techniques exist for exploring various aspects of the pathobiology of the endothelium. As endothelial dysfunction is a diffuse-systemic disorder, the peripheral arteries, because of their accessibility, represent the basis for assessment of endothelial dysfunction. Flow-mediated dilation (FMD) of the peripheral conduit arteries is one of the most widely used tests of endothelial function. FMD measures the endothelial vasomotor response during reactive hyperemia, but it does not provide information concerning the control of arterial tone at rest. A new technique, low-flow-mediated constriction (L-FMC), provides complementary information to that by FMD, quantifying the decrease in the forearm conduit artery diameter that occurs in response to the decrease in blood flow during occlusion. This indicated that the L-FMC response is not based on nitric oxide availability but it might be mediated by other substances, providing a coordinated effect of vasodilation and its inhibition; therefore, simultaneous determination of FMD and L-FMC may provide comprehensive information on vascular homeostasis.Peripheral arterial tonometry (PAT) evaluates pulse wave amplitude, which is linked to endothelial function. Like FMD, PAT has also been shown to be reduced in the presence of risk factors, as well as in patients with atherosclerosis; however, FMD of the brachial artery and PAT are very different methods for identification of the vascular reactivity of different arterial territories. FMD directly registers the dilation capability of the large-conduit artery, whereas PAT measures flow response hyperemia, which is related to the endothelial function of small arteries and to the endothelial function of the microcirculation. Therefore, this technique is mostly used for investigation of the functional capability of the microcirculation.Determination of venous endothelial dysfunction is more complicated and invasive and is less reproducible. Micro-invasive techniques such as the dorsal hand vein technique and radionuclide assessment of changes in volume of the legs provide limited information about venous endothelial health; however, as endothelial dysfunction is expected to be a systemic disorder affecting the complete circulatory system, determination of the endothelial function of peripheral arteries also gives insight into venous functional status.