Non-invasive measurement of human endothelium dependent arterial responses: accuracy and reproducibility.

Abstract

Objective-To assess a non-invasive test for endothelial dysfunction, an important early event in the atherogenic process. Methods-Using high resolution ultrasound, the accuracy of detecting small changes in vessel diameter was assessed using phantom "arteries", and the same equipment was then used to measure flow mediated dilatation in the brachial artery of 40 healthy adults aged 22-51 years, studied on four occasions; intervals between scans were 1-2 days, 1-2 weeks, and 2-4 months. Results-Differences between pairs of phantom "arteries" with diameters 0-1-0'2 mm apart were correctly estimated in 162 of 264 cases (61%); no measurement by any of four independent observers was > 041 mm in error, and the mean error was 0*04 mm. For in vivo scans, the overall coefficient of variation for flow mediated dilatation was 1-8% (1.6% for women, 1-9% for men, P = 0.18). In 34/40 subjects (85%), all values for flow mediated dilatation were within 2-5% of the overall mean for each subject. A nested analysis of variance showed the expected between patient variability, and also significant day to day variation, but little between weeks or months. Using these data to generate power function analyses, we calculated that for individuals, an improvement in flow mediated dilatation of 4-8% is significantly greater than natural variability. In clinical trials, a mean improvement in flow mediated dilatation of at least 2% would usually be required to detect a treatment benefit, with much larger subject numbers needed for a parallel group compared to a crossover trial design. Conclusions-Vascular responses to endothelium dependent and independent stimuli in systemic arteries can be studied non-invasively in man. Subjects should be studied on at least two occasions before and after any intervention, to optimise the chance of showing a significant effect from any potentially beneficial therapy. (Br Heart J 1995;74:247-253).

Beta-blockers do not impair the cardiovascular benefits of endurance training in hypertensives

“…21,22 By means of highresolution ultrasound, diameter changes in response to reactive hyperaemia (flow-mediated vasodilation, FMD) and glyceroltrinitrate (GTN), were measured, according to standard protocols. [22][23][24][25] Accuracy and reproducibility of the method had been documented previously. 21,22 Flow-mediated vasodilation in response to reactive hyperaemia (FMD) represents endothelium-dependent vasoreactivity, whereas vasodilation in response to GTN indicates smooth muscle-cell function and is independent of endothelial function.…”

Effects of low-dose combination therapy with an angiotensin-converting enzyme inhibitor and a diuretic on flow-mediated vasodilation in hypertensive patients: a 6-month, single-center study

“…Brachial artery endothelial cell function was assessed at baseline and at the end of the study period using a previously validated technique. 14,15 The diameter of the target artery was measured from 2-dimensional sonograms. A 7.5-MHz linear phased-array ultrasound transducer attached to an ImagePoint ultrasound system (Hewlett-Packard Company, Palo Alto, California) was used; the operating parameters of the equipment were not changed during the study.…”

The endothelial cell in health and disease: its function, dysfunction, measurement and therapy

“…3,16,22,58 It is widely used in clinical research trials and predicts coronary artery disease, 45 postoperative cardiac events 46 and long-term cardiovascular events. 29,39,[51][52][53] Attention to detail is essential to ensure accurate and reproducible measurements using highfrequency ultrasound; a summary of the technique is presented.…”

“…29,39,[51][52][53] Attention to detail is essential to ensure accurate and reproducible measurements using highfrequency ultrasound; a summary of the technique is presented. 3,22,58 Testing should be performed by an experienced sonographer, in the morning, after an overnight fast, in a temperature-controlled room (B22 1C), with the subject supine, and after a rest period so that a steady baseline is reached. The subject's arm should be extended with the hand supinated, then immobilized, exposing the brachial artery in a constant position for imaging.…”