What methods are used to diagnose endothelial dysfunction?

From the Guidelines

Endothelial dysfunction can be diagnosed primarily through flow-mediated dilation (FMD), which is considered the gold standard, as it directly assesses the endothelium's ability to produce nitric oxide and cause vasodilation in response to shear stress 1. To perform FMD, follow these steps:

• Have the patient rest supine for 10 minutes in a quiet, temperature-controlled room.
• Use ultrasound to measure the baseline diameter of the brachial artery.
• Inflate a blood pressure cuff on the forearm to 50 mmHg above systolic pressure for 5 minutes.
• Deflate the cuff and measure the artery diameter again at 60-90 seconds post-deflation.
• Calculate the percent change in artery diameter; a change less than 10% indicates endothelial dysfunction.

Another non-invasive option is peripheral arterial tonometry (PAT), which measures changes in fingertip blood volume during reactive hyperemia. This test is easier to perform and less operator-dependent than FMD 1. Additionally, biochemical markers such as asymmetric dimethylarginine (ADMA), von Willebrand factor, and E-selectin can be measured in blood samples to assess endothelial function. However, these are less specific and typically used in conjunction with other tests.

These tests are effective because they assess the endothelium's ability to produce nitric oxide and cause vasodilation in response to shear stress, which is a key function of healthy endothelial cells. Impaired vasodilation indicates endothelial dysfunction, a precursor to atherosclerosis and cardiovascular disease. The most recent and highest quality study 1 supports the use of FMD and PAT as diagnostic tools for endothelial dysfunction, and provides normal values for brachial FMD in different age ranges.

Some key points to consider when performing these tests include:

• The technique used to measure FMD can affect the results, and laboratories should select the method that gives them the most reproducible results 1.
• The flow stimulus should be consistent, and peak hyperemic flows should be reported 1.
• The baseline diameter of the brachial artery can affect the results, and changes in baseline diameter should be taken into account when interpreting the results 1.
• PAT is a promising technique that appears to be relatively operator-independent and has good reproducibility in children 1.

Overall, FMD and PAT are the most effective diagnostic tools for endothelial dysfunction, and should be used in conjunction with other tests to assess endothelial function and cardiovascular risk.

From the Research

Methods for Diagnosing Endothelial Dysfunction

The diagnosis of endothelial dysfunction can be achieved through various methods, including:

• Biochemical methods: measuring NO metabolites and pro-inflammatory and vasoconstrictor mediators released by the endothelium 2
• Physical methods: divided into invasive and non-invasive methods 3
• Non-invasive methods:
  • Flow-mediated dilation (FMD) of the brachial artery by ultrasounds: the most widely used vascular test to assess endothelium-dependent vasodilation 3, 4, 5, 6
  • Measurement of microcirculatory reactive hyperaemia by forearm venous pletysmography or digital pulse amplitude tonometry 4
  • Response to beta2 agonist by applanation tonometry or digital photoplethysmography 4
  • Skin laser doppler 4
  • Peripheral arterial tonometry (PAT): evaluates pulse wave amplitude, which is linked to endothelial function 5
  • 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 5
• Invasive methods:
  • Intra-coronary injections 2
  • Dorsal hand vein technique 5
  • Radionuclide assessment of changes in volume of the legs 5

Advantages and Limitations of Each Method

Each method has its advantages and limitations, including:

• FMD: non-invasive, safe, and repeatable, but requires qualified and experienced medical staff 3
• PAT: measures flow response hyperemia, which is related to the endothelial function of small arteries and to the endothelial function of the microcirculation 5
• L-FMC: provides complementary information to that by FMD, but its response is not based on nitric oxide availability 5
• Biochemical methods: allow measuring NO metabolites and pro-inflammatory and vasoconstrictor mediators released by the endothelium, but have limited role in the assessment of individual patients due to biological and assay availability and variability 4