Endothelial Dysfunction - Assessment Part 1

Measuring Endothelial Dysfunction 

Dicken Weatherby, N.D. and Beth Ellen DiLuglio, MS, RDN, LDN

Endothelial dysfunction and disruption are suspect in cardiac disease but may also underlie dermatological, gastrointestinal, hepatic, immunological, renal, and vascular disease. Its presence may be overlooked but its consequences will not go unnoticed.[i]

There may be no overt signs or symptoms of endothelial dysfunction itself and atherosclerosis has a long “silent” asymptomatic phase.[ii]

However, in progressing stages of atherosclerosis and cardiovascular endothelial dysfunction, angina can be a telltale sign. Supplementation with 6-9 grams of L-arginine was found to reduce angina and blood pressure and improve endothelial function in CVD patients.[iii]

Measuring endothelial dysfunction

Endothelial dysfunction has been recognized as an underlying cause of atherosclerosis and cardiovascular disease for decades… it was first measured in 1986.

Available methods of measuring endothelial dysfunction include[iv] [v] [vi] [vii] [viii]

  • Doppler flow guide wire
  • Intra-arterial infusion of vasoactive agents (e.g. acetylcholine) using coronary angiography, ultrasound
  • Flow-mediated dilation of the brachial artery (most common)
  • Mercury-filled Silastic strain-gauge plethysmography
  • Nitroglycerine-induced vasodilation
  • Oscillometric measurement of vascular response
  • Reactive- hyperemia-peripheral arterial tonometry (PAT) evaluation of pulse wave amplitude
  • Carotid Duplex Ultrasound
  • Pulse Wave Velocity (PWV)
  • Pressure Pulsation Signal

The noninvasive “cold pressor test” is an interesting test that evaluates sympathetic-mediated release of NO following submersion of a subject’s hand in cold water for 2 minutes. Vasoconstriction versus vasodilation will prevail in dysfunctional endothelium. Hyper-reactors to the cold stimulus will mount a hypertensive response.[ix]

At present, the most convenient and available tool for measuring endothelial dysfunction is flow-mediated dilation (FMD). The test itself is a reflection of nitric oxide production.[x] This method stimulates the brachial artery endothelium to produce vasodilatory factors (e.g., nitric oxide) to help dilate the blood vessel and reduce tension.[xi]

The FMD test can be instrumental in predicting cardiovascular events in individuals without overt CVD risk.[xii]

Research has identified a group of individuals with endothelial dysfunction who lack commonly recognized cardiovascular risk factors. These individuals are active, maintain a healthy weight, have normal or low blood pressure, and are at low risk for metabolic syndrome.[xiii]

Therefore, even seemingly healthy individuals with no signs of CVD may be at risk for endothelial dysfunction evidenced by impaired response to vasodilators bradykinin and acetylcholine.[xiv]

In part 2, we'll be covering Endothelial Dysfunction and Blood Biomarkers

Research

[i] Widmer, R Jay, and Amir Lerman. “Endothelial dysfunction and cardiovascular disease.” Global cardiology science & practice vol. 2014,3 291-308. 16 Oct. 2014, 

[ii] Park, Kyoung-Ha, and Woo Jung Park. “Endothelial Dysfunction: Clinical Implications in Cardiovascular Disease and Therapeutic Approaches.” Journal of Korean medical science vol. 30,9 (2015): 1213-25. 

[iii] Widmer, R Jay, and Amir Lerman. “Endothelial dysfunction and cardiovascular disease.” Global cardiology science & practice vol. 2014,3 291-308. 16 Oct. 2014, 

[iv] Higashi, Yukihito. “Assessment of endothelial function. History, methodological aspects, and clinical perspectives.” International heart journal vol. 56,2 (2015): 125-34. 

[v] Widmer, R Jay, and Amir Lerman. “Endothelial dysfunction and cardiovascular disease.” Global cardiology science & practice vol. 2014,3 291-308. 16 Oct. 2014.

[vi] Jezovnik, Mateja K. "How to assess endothelial function for detection of pre-clinical atherosclerosis." E-journal Cardiology Practice 10.22 (2011): 10.

[vii] Cedars Sinai Women’s Heart Center. Endothelial Function Testing.

[viii] Al-Qaisi, Mo et al. “Measurement of endothelial function and its clinical utility for cardiovascular risk.” Vascular health and risk management vol. 4,3 (2008): 647-52.

[ix] Barthelmes, Jens et al. “Endothelial dysfunction in cardiovascular disease and Flammer syndrome-similarities and differences.” The EPMA journal vol. 8,2 99-109. 6 Jun. 2017.

[x] Higashi, Yukihito. “Assessment of endothelial function. History, methodological aspects, and clinical perspectives.” International heart journal vol. 56,2 (2015): 125-34.

[xi] Zehr, Kayla R, and Mary K Walker. “Omega-3 polyunsaturated fatty acids improve endothelial function in humans at risk for atherosclerosis: A review.” Prostaglandins & other lipid mediators vol. 134 (2018): 131-140.

[xii] Zehr, Kayla R, and Mary K Walker. “Omega-3 polyunsaturated fatty acids improve endothelial function in humans at risk for atherosclerosis: A review.” Prostaglandins & other lipid mediators vol. 134 (2018): 131-140.

[xiii] Barthelmes, Jens et al. “Endothelial dysfunction in cardiovascular disease and Flammer syndrome-similarities and differences.” The EPMA journal vol. 8,2 99-109. 6 Jun. 2017.

[xiv] Sitia, S et al. “From endothelial dysfunction to atherosclerosis.” Autoimmunity reviews vol. 9,12 (2010): 830-4.

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