Flow-mediated dilation

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Flow-mediated dilation (FMD) refers to dilation (widening) of an artery when blood flow increases in that artery. [1] [2] The primary cause of FMD is release of nitric oxide by endothelial cells. [1]

Contents

To determine FMD, brachial artery dilation following a transient period of forearm ischemia is measured using ultrasound. [3] Because the value of FMD can be compromised when improperly applied, attempts have been made to standardize the methodology for measuring FMD. [4]

Clinical significance

FMD is a noninvasive measure of blood vessel health (endothelial dysfunction [5] [6] ) which (when low) is at least as predictive of cardiovascular disease as traditional risk factors. [4] [7] [8] Major cardiovascular disease associated with low FMD include cardiac death, myocardial infarction, and stroke. [8]

Low FMD is a stronger predictor of future cardiovascular disease events in patients with existing cardiovascular disease than in healthy normal persons. [8] 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. [9]

FMD is a sensitive marker for the amount of blood vessel damage caused by cigarette smoke. [10] So-called light cigarettes (having reduced tar and nicotine) were shown to impair FMD as much as regular cigarettes. [10]

Improved FMD results in greater perfusion and oxygen supply to peripheral tissue. [11]

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). [12]

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. [13] ET-1 has autocrine action on endothelial cells causing the release of nitric oxide. [13] 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. [14] The suppression of endothelium production of nitric oxide is the result of oxidative stress on the vasculature. [15] Similar to the effects of salt, a high-fat meal can increase oxidative stress, reduce nitric oxide availability and reduce FMD. [16]

A study of randomized controlled trials of the effects of cocoa and chocolate suggested a reciprocal relationship between insulin resistance and endothelia function (FMD). [17] Both cocoa and chocolate increase FMD in a dose-dependent manner, believed to be related to a reduction in cardiovascular disease risk. [18]

The clinical value of FMD is limited by the fact that FMD is difficult to measure, requiring a skilled and well-trained clinician. [7]

Effects of exercise

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. [19] The reduction of leg FMD caused by prolonged sitting can be reduced by fidgeting (periodic leg movement). [20]

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. [21]

Forty-five minutes of cycling exercise before sitting has been shown to eliminate the impaired leg FMD due to three hours of sitting. [22] Athletes over age 40 show greater FMD than their age-matched peers. [3]

A meta-analysis of 182 subjects showed twice the improvement in FMD resulting from high-intensity interval training compared to endurance training. [11]

See also

Related Research Articles

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References

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  2. ↑ Tremblay JC, Pyke KE (2018). "Flow-mediated dilation stimulated by sustained increases in shear stress: a useful tool for assessing endothelial function in humans?". American Journal of Physiology. Heart and Circulatory Physiology . 314 (3): H508–H520. doi:10.1152/ajpheart.00534.2017. PMC   5899264 . PMID   29167121.
  3. 1 2 Montero D, Padilla J, Diaz-Cañestro C, Muris DM, Pyke KE, Obert P, Walther (2014). "Flow-mediated dilation in athletes: influence of aging". Medicine & Science in Sports & Exercise . 46 (11): 2148–2158. doi: 10.1249/MSS.0000000000000341 . PMID   24963792.
  4. 1 2 Thijssen DH, Black MA, Pyke KE, Padilla J, Atkinson G, Harris RA, Parker B, Widlansky ME, Tschakovsky ME, Green DJ (2011). "Assessment of flow-mediated dilation in humans: a methodological and physiological guideline". American Journal of Physiology . 300 (1): H2–H12. doi:10.1152/ajpheart.00471.2010. PMC   3023245 . PMID   20952670.
  5. ↑ 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 (2017). "Endothelial dysfunction assessment by flow-mediated dilation in a high-altitude population". Vascular Health and Risk Management . 13: 421–426. doi: 10.2147/VHRM.S151886 . PMC   5701560 . PMID   29200863.
  6. ↑ Kuro-O M (2019). "The Klotho proteins in health and disease". Nature Reviews Nephrology . 15 (1): 27–44. doi:10.1038/s41581-018-0078-3. PMID   30455427. S2CID   53872296.
  7. 1 2 Fekete AA, Givens DI, Lovegrove JA (2016). "Can milk proteins be a useful tool in the management of cardiometabolic health? An updated review of human intervention trials". Proceedings of the Nutrition Society . 75 (3): 328–341. doi: 10.1017/S0029665116000264 . PMID   27150497.
  8. 1 2 3 Ras RT, Streppel MT, Draijer R, Zock PL (2013). "Flow-mediated dilation and cardiovascular risk prediction: a systematic review with meta-analysis". International Journal of Cardiology . 168 (1): 344–351. doi:10.1016/j.ijcard.2012.09.047. PMID   23041097.
  9. ↑ Khan AA, Thomas GN, Lip G, Shantsila A (2020). "Endothelial function in patients with atrial fibrillation". Annals of Medicine . 52 (1–2): 1–11. doi:10.1080/07853890.2019.1711158. PMC   7877921 . PMID   31903788.
  10. 1 2 Messner B, Bernhard D (2014). "Smoking and cardiovascular disease: mechanisms of endothelial dysfunction and early atherogenesis". Arteriosclerosis, Thrombosis, and Vascular Biology . 34 (3): 509–515. doi: 10.1161/ATVBAHA.113.300156 . PMID   24554606.
  11. 1 2 Cassidy S, Thoma C, Houghton D, Trenell MI (2017). "High-intensity interval training: a review of its impact on glucose control and cardiometabolic health". Diabetologia . 60 (1): 7–23. doi:10.1007/s00125-016-4106-1. PMC   6518096 . PMID   27681241.
  12. ↑ Shechter, Michael (January 1, 2014). "Usefulness of Brachial Artery Flow-Mediated Dilation to Predict Long-Term Cardiovascular Events in Subjects Without Heart Disease". The American Journal of Cardiology. 113 (1): 162–167. doi: 10.1016/j.amjcard.2013.08.051 . PMID   24169007 . Retrieved 15 December 2017.
  13. 1 2 Dickinson KM, Clifton PM, Keogh JB (2014). "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". Atherosclerosis . 233 (1): 32–38. doi:10.1016/j.atherosclerosis.2013.11.078. PMID   24529119.
  14. ↑ Jablonski KL, Racine ML, Seals DR (2013). "Dietary sodium restriction reverses vascular endothelial dysfunction in middle-aged/older adults with moderately elevated systolic blood pressure". Journal of the American College of Cardiology . 61 (3): 335–343. doi:10.1016/j.jacc.2012.09.010. PMC   3549053 . PMID   23141486.
  15. ↑ Greaney JL, DuPont JJ, Farquhar WS (2012). "Dietary sodium loading impairs microvascular function independent of blood pressure in humans: role of oxidative stress". The Journal of Physiology . 590 (21): 5519–5528. doi:10.1113/jphysiol.2012.236992. PMC   3515835 . PMID   22907057.
  16. ↑ Fewkes JJ, Kellow NJ, Dordevic AL (2022). "A single, high-fat meal adversely affects postprandial endothelial function: a systematic review and meta-analysis". The American Journal of Clinical Nutrition . 116 (3): 699–729. doi:10.1093/ajcn/nqac153. PMC   9437993 . PMID   35665799.
  17. ↑ Hooper L, Kay C, Cassidy A (2012). "Effects of chocolate, cocoa, and flavan-3-ols on cardiovascular health: a systematic review and meta-analysis of randomized trials". The American Journal of Clinical Nutrition . 95 (3): 740–751. doi:10.3945/ajcn.111.023457. PMID   22301923.
  18. ↑ Kevin D Monahan KD (2012). "Effect of cocoa/chocolate ingestion on brachial artery flow-mediated dilation and its relevance to cardiovascular health and disease in humans". Archives of Biochemistry and Biophysics . 527 (2): 90–94. doi:10.1016/j.abb.2012.02.021. PMID   22425756.
  19. ↑ Boyle LJ, Credeur DP, Jenkins NT, Padilla J, Leidy HJ, Thyfault JP, Fadel PJ (2013). "Impact of reduced daily physical activity on conduit artery flow-mediated dilation and circulating endothelial microparticles". Journal of Applied Physiology . 115 (10): 1519–1525. doi:10.1152/japplphysiol.00837.2013. PMC   3841822 . PMID   24072406.
  20. ↑ Morishima T, Restaino RM, Walsh LK, Kanaley JA, Fadel PJ, Padilla J (2016). "Prolonged sitting-induced leg endothelial dysfunction is prevented by fidgeting". American Journal of Physiology . 311 (1): H177–H182. doi:10.1152/ajpheart.00297.2016. PMC   4967200 . PMID   27233765.
  21. ↑ Seals DR (2014). "Edward F. Adolph Distinguished Lecture: The remarkable anti-aging effects of aerobic exercise on systemic arteries". Journal of Applied Physiology . 117 (5): 425–239. doi:10.1152/japplphysiol.00362.2014. PMC   4157159 . PMID   24855137.
  22. ↑ Morishima T, Restaino RM, Walsh LK, Kanaley JA, Padilla J (2017). "Prior exercise and standing as strategies to circumvent sitting-induced leg endothelial dysfunction". Clinical Science . 131 (11): 1045–1053. doi:10.1042/CS20170031. PMC   5516793 . PMID   28385735.
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