BlueCross BlueShield of Tennessee Medical Policy Manual

Endothelial Function Assessment


Endothelial (the inner lining of blood vessels) functional assessment (e.g. EndoPAT 2000) is being investigated as a tool to identify cardiovascular disease risk through diagnosing endothelial dysfunction. Noninvasive techniques for measuring endothelial function include brachial artery ultrasound and peripheral artery tonometry (PAT).

The primary function of the endothelium is to regulate vascular tone and structure, providing the balance between vasodilation and vasoconstriction. It is believed that the inner layer of the coronary artery, the endothelium, becomes damaged with age, especially in individuals with cardiovascular disease, type II diabetes mellitus, hypertension, obesity, renal failure, and hypercholesterolemia.

Brachial artery flow-mediated dilation (FMD) has been the most widely used noninvasive method to evaluate endothelial function. The baseline brachial artery diameter and blood velocity are obtained via ultrasonography, and then the blood flow is occluded for a specified amount of time, usually by a standard blood pressure cuff placed on the arm. When the cuff is released, the acute increase in blood flow through the vessels (hyperemia), triggers several physiological responses that result in smooth muscle relaxation and vasodilation. Brachial artery vasodilation and blood velocity occlusion are again measured by ultrasound. The calculated increase in diameter and velocity from baseline after the cuff is removed reflects endothelium dependent vasodilation. This method has limitations of expensive equipment, lack of standardization, and extensive sonographer training.

Peripheral arterial tonometry (PAT) is a similar technique to brachial FMD; however it measures hyperemia-induced changes in several small vessels in the fingertip by pulse volume amplitude. PAT utilizes a standard blood pressure cuff placed around the bicep. Special finger sensors containing volume-sensing probes are placed over the index finger of each hand to monitor the function of the blood vessels. The sensors are connected to a recording device. After the blood pressure cuff is deflated, the finger sensors monitor reactive hyperemia. The PAT system automatically converts the changes in the peripheral arterial tone into a graph, which is used to assess the blood vessels and their hyperemic response before, during, and after the arm cuff was used. This system is different in that the hyperemia-induced changes are measured by an automated system, whereas changes elicited by the brachial FMD rely on the observation and expertise of the operator.




There is insufficient evidence in the peer-reviewed literature to support the effectiveness and clinical utility of endothelial function assessment in establishing the risk of cardiovascular disease.


Flammer, A. J., Anderson, T., Celermajer, D. S., Creager, M. A., Deanfield, J., Ganz, P., et al. (2012). The assessment of endothelial function - from research into clinical practice. Circulation, 126 (6), 753-767. (Level 2 evidence)

Hamburg, N. M., Keyes, M. J., Larson, M. G., Vasan, R. S., Schnabel, R., Pryde, M. M., et al. (2008). Cross-sectional relations of digital vascular function to cardiovascular risk factors in The Framingham Heart Study. Circulation, 117 (19), 2467-2474. (Level 3 evidence)

Higashi, Y. (2015). Assessment of endothelial function. History, methodological aspects, and clinical perspectives. International Heart Journal, 56 (2), 125-134. (Level 5 evidence)

Hudgins, L. C., Annavajjhala, V., Kovanlikaya, A., Frank, M. D., Solomon, A., Parker, T. S., et al. (2016). Non-invasive assessment of endothelial function in children with obesity and lipid disorders. Cardiology in the Young, 26 (3), 532-538. Abstract retrieved April 12, 2016 from PubMed database.

Matsuzawa, Y., Li, J., Aoki, T., Guddeti, R., Kwon, T., Cilluffo, R., et al. (2015) Predictive value of endothelial function by non-invasive peripheral arterial tonometry for coronary artery disease. Coronary Artery Disease, 26 (3), 231-238. (Level 3 evidence)

Souza, E. G., De Lorenzo, A., Huguenin, G., Oliveira, G. M., & Tibirica, E. (2014). Impairment of systemic microvascular endothelial and smooth muscle function in individuals with early-onset coronary artery disease: studies with laser speckle contrast imaging. Coronary Artery Disease, 25 (1), 23-28. Abstract retrieved April 12, 2016 from PubMed database.

Suessenbacher, A., Dorler, J., Wanitschek, M., Alber, H., Pachinger, O., & Frick, M. (2014). Prognostic value of peripheral arterial tonometry in patients with coronary artery disease and a high cardiovascular risk profile. Journal of Atherosclerosis and Thrombosis, 21 (3), 230-238. Abstract retrieved April 20, 2016 from PubMed database.

U. S. Food and Drug Administration. (2003, November). Center for Devices and Radiological Health. 510(k) Premarket Notification Database. K032519 (EndoPAT 2000). Retrieved April 12, 2016 from 

Van den Heuvel, M., Sorop, O. Musters, P., van Domburg, R., Galema, T., Duncker, D., et. al. (2015, May) Peripheral arterial tonometry cannot detect patients at low risk of coronary artery disease. Netherlands Heart Journal. 23, 468-474. (Level 3 evidence)

Winifred S. Hayes, Inc. Medical Technical Directory. (2014, December; last update search December 2017). Noninvasive peripheral arterial tonometry. Retrieved January 31, 2019 from (42 articles and/or guidelines reviewed)




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