flow-mediated dilation

FMD is a noninvasive measure of blood vessel health (endothelial dysfunction{{cite journal | vauthors=Calderón-Gerstein WS, López-Peña A, Macha-Ramírez R, Bruno-Huamán A, Espejo-Ramos R, Vílchez-Bravo S, Ramírez-Breña M, Damián-Mucha M, Matos-Mucha A | title=Endothelial dysfunction assessment by flow-mediated dilation in a high-altitude population | journal= Vascular Health and Risk Management | volume=13 | pages=421–426 | year=2017 | doi= 10.2147/VHRM.S151886 | pmc=5701560 | pmid = 29200863 | doi-access=free }}{{cite journal | author=Kuro-O M | title=The Klotho proteins in health and disease | journal=Nature Reviews Nephrology | volume=15 | issue=1 | pages=27–44 | year=2019 | doi = 10.1038/s41581-018-0078-3 | pmid=30455427 | s2cid=53872296 }}) which (when low) is at least as predictive of cardiovascular disease as traditional risk factors.{{cite journal | vauthors=Thijssen DH, Black MA, Pyke KE, Padilla J, Atkinson G, Harris RA, Parker B, Widlansky ME, Tschakovsky ME, Green DJ | title=Assessment of flow-mediated dilation in humans: a methodological and physiological guideline | journal= American Journal of Physiology | volume=300 | issue=1 | pages=H2–H12 | year=2011 | doi= 10.1152/ajpheart.00471.2010 | pmid = 20952670 | pmc=3023245 }}{{cite journal | vauthors=Fekete AA, Givens DI, Lovegrove JA | title=Can milk proteins be a useful tool in the management of cardiometabolic health? An updated review of human intervention trials | journal= Proceedings of the Nutrition Society | volume=75 | issue=3 | pages=328–341 | year=2016 | doi= 10.1017/S0029665116000264 | pmid=27150497 | doi-access=free }} Major cardiovascular disease associated with low FMD include cardiac death, myocardial infarction, and stroke.{{cite journal | vauthors=Ras RT, Streppel MT, Draijer R, Zock PL | title=Flow-mediated dilation and cardiovascular risk prediction: a systematic review with meta-analysis | journal= International Journal of Cardiology | volume=168 | issue=1 | pages=344–351 | year=2013 | doi= 10.1016/j.ijcard.2012.09.047 | pmid=23041097 }}

Low FMD is a stronger predictor of future cardiovascular disease events in patients with existing cardiovascular disease than in healthy normal persons. Patients with atrial fibrillation have reduced FMD, but it has not been determined whether there is a causal relationship or if FMD is simply a marker of a causal factor.{{cite journal | vauthors = Khan AA, Thomas GN, Lip G, Shantsila A | title=Endothelial function in patients with atrial fibrillation | journal= Annals of Medicine | volume=52 | issue=1–2 | pages=1–11 | year=2020 | doi= 10.1080/07853890.2019.1711158 | pmc=7877921 | pmid=31903788 }}

FMD is a sensitive marker for the amount of blood vessel damage caused by cigarette smoke.{{cite journal | vauthors=Messner B, Bernhard D | title=Smoking and cardiovascular disease: mechanisms of endothelial dysfunction and early atherogenesis | journal= Arteriosclerosis, Thrombosis, and Vascular Biology | volume=34 |issue=3 | pages=509–515| year=2014 | doi=10.1161/ATVBAHA.113.300156 | pmid = 24554606 | doi-access=free }} So-called light cigarettes (having reduced tar and nicotine) were shown to impair FMD as much as regular cigarettes.

Improved FMD results in greater perfusion and oxygen supply to peripheral tissue.{{cite journal | vauthors=Cassidy S, Thoma C, Houghton D, Trenell MI | title=High-intensity interval training: a review of its impact on glucose control and cardiometabolic health | journal= Diabetologia | volume=60 | issue=1 | pages=7–23 | year=2017 | doi= 10.1007/s00125-016-4106-1 | pmid = 27681241 | pmc=6518096}}

An Israeli study of 618 healthy subjects found FMD to be an excellent predictor of long-term adverse cardiovascular events. Participants with below-mean FMD were 278% more likely to experience cardiovascular events during the 4.6 year average follow-up period than participant with above-mean FMD (95% Confidence Interval: 135-571%, p-value<0.001).{{cite journal|last1=Shechter|first1=Michael|title=Usefulness of Brachial Artery Flow-Mediated Dilation to Predict Long-Term Cardiovascular Events in Subjects Without Heart Disease|journal=The American Journal of Cardiology|date=January 1, 2014|volume=113|issue=1|pages=162–167|url=http://www.ajconline.org/article/S0002-9149(13)01964-4/fulltext|accessdate=15 December 2017|doi=10.1016/j.amjcard.2013.08.051|pmid=24169007 |doi-access=free}}

Normotensive overweight/obese patients who were salt restricted for six weeks showed an endothelin 1 (ET-1) decrease of 14% associated with a 45% increase in FMD.{{cite journal | vauthors = Dickinson KM, Clifton PM, Keogh JB| title=A reduction of 3 g/day from a usual 9 g/day salt diet improves endothelial function and decreases endothelin-1 in a randomised cross_over study in normotensive overweight and obese subjects | journal= Atherosclerosis | volume=233 | issue=1 | pages=32–38 | year=2014 | doi= 10.1016/j.atherosclerosis.2013.11.078 | pmid=24529119}} ET-1 has autocrine action on endothelial cells causing the release of nitric oxide. Another study using middle-aged or older adults with moderately elevated blood pressure taking sodium chloride tablets or placebo tablets for a few weeks showed that sodium restriction increased nitric oxide and tetrahydrobiopterin (BH4) resulting in improved FMD without affecting blood pressure.{{cite journal | vauthors = Jablonski KL, Racine ML, Seals DR | title=Dietary sodium restriction reverses vascular endothelial dysfunction in middle-aged/older adults with moderately elevated systolic blood pressure | journal= Journal of the American College of Cardiology | volume=61 | issue=3 | pages=335–343 | year=2013 | doi= 10.1016/j.jacc.2012.09.010 | pmc=3549053 | pmid=23141486}} The suppression of endothelium production of nitric oxide is the result of oxidative stress on the vasculature.{{cite journal | vauthors = Greaney JL, DuPont JJ, Farquhar WS | title=Dietary sodium loading impairs microvascular function independent of blood pressure in humans: role of oxidative stress | journal= The Journal of Physiology | volume=590 | issue=21 | pages=5519–5528 | year=2012 | doi= 10.1113/jphysiol.2012.236992 | pmc=3515835 | pmid=22907057}} Similar to the effects of salt, a high-fat meal can increase oxidative stress, reduce nitric oxide availability and reduce FMD.{{cite journal | vauthors = Fewkes JJ, Kellow NJ, Dordevic AL | title=A single, high-fat meal adversely affects postprandial endothelial function: a systematic review and meta-analysis | journal= The American Journal of Clinical Nutrition | volume=116 | issue=3 | pages=699–729 | year=2022 | doi= 10.1093/ajcn/nqac153 | pmc=9437993 | pmid=35665799}}

A study of randomized controlled trials of the effects of cocoa and chocolate suggested a reciprocal relationship between insulin resistance and endothelia function (FMD).{{cite journal | vauthors = Hooper L, Kay C, Cassidy A | title=Effects of chocolate, cocoa, and flavan-3-ols on cardiovascular health: a systematic review and meta-analysis of randomized trials | journal= The American Journal of Clinical Nutrition | volume=95 | issue=3 | pages=740–751 | year=2012 | doi= 10.3945/ajcn.111.023457 | pmid=22301923}} Both cocoa and chocolate increase FMD in a dose-dependent manner, believed to be related to a reduction in cardiovascular disease risk.{{cite journal | author = Kevin D Monahan KD | title=Effect of cocoa/chocolate ingestion on brachial artery flow-mediated dilation and its relevance to cardiovascular health and disease in humans | journal= Archives of Biochemistry and Biophysics | volume=527 | issue=2 | pages=90–94 | year=2012 | doi= 10.1016/j.abb.2012.02.021 | pmid=22425756}}

The clinical value of FMD is limited by the fact that FMD is difficult to measure, requiring a skilled and well-trained clinician.

A study of healthy young men who normally take over 10,000 steps per day, but were restricted to less than 5,000 steps per day for five days showed impaired FMD in the popliteal (leg) artery, but not the brachial (arm) artery.{{cite journal | vauthors=Boyle LJ, Credeur DP, Jenkins NT, Padilla J, Leidy HJ, Thyfault JP, Fadel PJ | title=Impact of reduced daily physical activity on conduit artery flow-mediated dilation and circulating endothelial microparticles | journal= Journal of Applied Physiology | volume=115 | issue=10 | pages=1519–1525| year=2013| doi=10.1152/japplphysiol.00837.2013| pmid = 24072406 | pmc=3841822 }} The reduction of leg FMD caused by prolonged sitting can be reduced by fidgeting (periodic leg movement).{{cite journal | vauthors=Morishima T, Restaino RM, Walsh LK, Kanaley JA, Fadel PJ, Padilla J | title=Prolonged sitting-induced leg endothelial dysfunction is prevented by fidgeting | journal= American Journal of Physiology | volume=311 | issue=1 | pages=H177–H182 | year=2016 | doi= 10.1152/ajpheart.00297.2016 | pmc=4967200 | pmid = 27233765 }}

An eight-week program of brisk walking resulted in a 50% increase in brachial artery FMD in middle-aged and older men, but failed to produce this benefit in estrogen-deficient post-menopausal women.{{cite journal | author=Seals DR | title=Edward F. Adolph Distinguished Lecture: The remarkable anti-aging effects of aerobic exercise on systemic arteries | journal= Journal of Applied Physiology | volume=117 | issue=5 | pages=425–239 | year=2014 | doi= 10.1152/japplphysiol.00362.2014 | pmc=4157159 | pmid = 24855137 }}

Forty-five minutes of cycling exercise before sitting has been shown to eliminate the impaired leg FMD due to three hours of sitting.{{cite journal | vauthors=Morishima T, Restaino RM, Walsh LK, Kanaley JA, Padilla J | title=Prior exercise and standing as strategies to circumvent sitting-induced leg endothelial dysfunction | journal= Clinical Science | volume=131 | issue=11 | pages=1045–1053 | year=2017 | url = http://www.clinsci.org/content/131/11/1045.long | doi= 10.1042/CS20170031 | pmc=5516793 | pmid = 28385735 }} Athletes over age 40 show greater FMD than their age-matched peers.

A meta-analysis of 182 subjects showed twice the improvement in FMD resulting from high-intensity interval training compared to endurance training.

• Atherosclerosis
• Hypercholesterolemia

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Category:Medical diagnosis

Category:Cardiovascular diseases