Methods for evaluating endothelial function: a position statement from the European Society of Cardiology Working Group on Peripheral Circulation

Abstract

The endothelium holds a pivotal role in cardiovascular health and disease. Assessment of its function was until recently limited to experimental designs due to its location. The advent of novel techniques has facilitated testing on a more detailed basis, with focus on distinct pathways. This review presents available in-vivo and ex-vivo methods for evaluating endothelial function with special focus on more recent ones. The diagnostic modalities covered include assessment of epicardial and microvascular coronary endothelial function, local vasodilation by venous occlusion plethysmography and flow-mediated dilatation, arterial pulse wave analysis and pulse amplitude tonometry, microvascular blood flow by laser Doppler flowmetry, biochemical markers and bioassays, measurement of endothelial-derived microparticles and progenitor cells, and glycocalyx measurements. Insights and practical information on the theoretical basis, methodological aspects, and clinical application in various disease states are discussed. The ability of these methods to detect endothelial dysfunction before overt cardiovascular disease manifests make them attractive clinical tools for prevention and rehabilitation. METHODS FOR EVALUATING ENDOTHELIAL FUNCTION. A POSITION STATEMENT FROM THE EUROPEAN SOCIETY OF CARDI-OLOGY WORKING GROUP ON PERIPHERAL CIRCULATION. John Venous occlusion plethysmographyVenous occlusion plethysmography (VOP), established more than 100 years ago, is the longest living method for investigating blood flow in humans. Flow-mediated dilatationConduit vessels respond to alterations in blood flow by increasing vessel diameter via an endothelial dependent mechanism. 20,21 The flow-mediated dilatation (FMD)technique measures changes in conduit artery diameter by ultrasound. This response has been shown to reflect local bioactivity of endothelial-derived NO. 22 MethodologyThe brachial artery is most often imaged (online Supplemental Figure 2). FMD studies are performed in a quiet temperature controlled room while subjects are lying supine for >10 min prior to image acquisition. A straight, non-branching segment of the brachial artery above the antecubital fossa is imaged in the longitudinal plane with the ultrasound probe securely fixed using a stereotactic clamp. This permits fine adjustments in the coronal and sagittal planes. A blood pressure cuff is placed 1-2 cm below the antecubital fossa and inflated to supra-systolic pressure. 23 After cuff release, reactive hyperaemia results and is quantified using Doppler. The arterial diameter is recorded at end diastole using electrocardiographic gating during image acquisition, to determine the response of the conduit artery to increase in flow. 24 Changes in the arterial diameter are assessed using commercial digital edge detection software. Pulse wave analysisThe arterial waveform contains important information about the stiffness of the large arteries and amount of wave reflection within the arterial system. 32 Wave reflection occurs at sites of impedance mismatc...

Testing Endothelial Function and its Clinical Relevance

“…Endothelial-dependent flow-mediated dilation of conduit arteries was one of the first non-invasive methods for clinical assessment of endothelial function, and its validity and applicability were defined in consensus documents 26) . It is an indicator of the vessel wall dilation capability of large conduit arteries.…”

“…FMD is not only as predictive as traditional risk factors but may also provide important additional prognostic individual information on the risk of cardiovascular events 25) . Therefore, assessment of endothelial function on the basis of FMD has been proposed as a possible non-invasive and inexpensive endpoint that could reflect the cumulative cardiovascular burden and the responsiveness to therapies in individual patients 16,26) .…”

Endothelial function assessment in atherosclerosis. Comparison of brachial artery flow‑mediated vasodilation and peripheral arterial tonometry

“…Clinical risk factors were defined as follows: hypercholesterolemia (total plasma cholesterol level >5 mmol/l); diabetes (fasting glucose level ≥7 mmol/l, hemoglobin A 1c >6.5%, or current treatment with insulin or oral hypoglycemic agents), hypertension (blood pressure according to the manufacturer's instructions and in accordance with the current literature. [12][13][14][15] Carotid artery intima-media thickness The IMT measurement was performed using the same device and by the same investigator. The measurements were taken using the standard method.…”

Insulin Resistance and not BMI is the Major Determinant of Early Vascular Impairment in Patients with Morbid Obesity

“…A blood pressure cuff was placed 1-2 cm below the antecubital fossa and inflated to suprasystolic pressure. The measurements of the basal and posthyperemia diameter were recorded at end-diastole, and the average of three measurements was used for the analysis 14) . The intraobserver between-occasion reproducibility of the FMV in our laboratory was assessed in 10 subjects examined two days apart.…”