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Ultrasound Assessment of Endothelial Function: A Technical Guideline of the Flow-mediated Dilation Test
Published on: April 27, 2016
The clinical relevance of the percentage flow-mediated dilation index
Greg Atkinson1, Alan M Batterham
1Health and Social Care Institute, School of Health and Social Care, Teesside University, Parkside West, Middlesbrough, Tees Valley, TS1 3BA, UK, greg.atkinson@tees.ac.uk.
Insights
Brachial artery flow-mediated dilation (FMD%) is not recommended for assessing coronary artery disease risk due to measurement errors and unclear clinical relevance. Its dependence on baseline artery size complicates interpretation.
Area of Science:
- Cardiovascular Research
- Medical Diagnostics
- Endothelial Function Studies
Background:
- The American College of Cardiology Foundation and American Heart Association previously did not recommend brachial artery percentage flow-mediated dilation (FMD%) for coronary artery disease (CAD) risk assessment in asymptomatic adults.
- Existing studies have primarily used correlation coefficients, which are insufficient for determining the clinical utility of FMD% as a substitute for coronary vasodilation.
Purpose of the Study:
- To critically evaluate the existing literature on the clinical utility of brachial artery FMD% for CAD risk assessment in asymptomatic adults.
- To determine if brachial FMD% is a suitable substitute for coronary vasodilation, considering methodological limitations and confounding factors.
Main Methods:
- Systematic review and critical analysis of past and recent studies investigating brachial artery FMD% and its correlation with coronary vasodilation.
- Examination of statistical methods used, focusing on the distinction between correlation coefficients and method agreement statistics.
- Assessment of the impact of baseline artery diameter, measurement error, and intervention-induced changes on FMD% interpretation.
Main Results:
- Method agreement statistics, not correlation coefficients, are required to assess if brachial FMD% can substitute for coronary vasodilation; current evidence suggests they are not closely related, even after accounting for baseline lumen diameter.
- The FMD% protocol requires specialist training and significant time (≥1 hour), with substantial measurement error and population reference range variability, limiting its robustness for individual clinical decisions.
- Interventions altering baseline artery diameter can bias FMD% estimates, and the FMD% index creates spurious correlations, potentially explaining paradoxical findings in obese individuals and athletes.
Conclusions:
- The clinical relevance of brachial artery flow-mediated dilation remains uncertain.
- The dependence of the FMD% index on initial artery size is a significant contributor to the lack of clarity regarding its clinical utility in assessing coronary artery disease risk.
Abstract:
In 2010, the American College of Cardiology Foundation and American Heart Association could not recommend brachial artery percentage flow-mediated dilation (FMD%) for risk assessment of coronary artery disease (CAD) in asymptomatic adults. We aimed to scrutinise past and recently published findings regarding FMD% in this same context of clinical utility and conclude that (1) the question of whether brachial FMD% is a suitable substitute for coronary vasodilation is addressed by method agreement statistics rather than the correlation coefficients that have been reported in past studies. Also, the much-repeated view that brachial FMD% and coronary vasodilation are "closely related" is not entirely justified, even before the influence of baseline lumen diameters on this relationship is accounted for; (2) along with the specialist training and the considerable time (≥1 h) that is required for the FMD% protocol, the error in individual measurements and population reference ranges is too large for clinical decisions to be robust on individual patients; (3) many interventions that are proposed to change FMD% also change baseline artery diameter, which can bias estimates of any intervention effects on the flow-mediated response per se, and (4) the FMD% index generates spurious correlations between shear rate, artery diameter and endothelial function, which may help to explain the apparent paradoxes of FMD% being higher in obese people and lower in athletes. In conclusion, the clinical relevance of brachial artery flow-mediated dilation is unclear at present. The dependence of the chosen index, FMD%, on initial artery size has contributed to this lack of clarity.

