Flow-mediated dilation

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]

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]

FMD is a sensitive marker for the amount of blood vessel damage caused by cigarette smoke.[9] So-called light cigarettes (having reduced tar and nicotine) were shown to impair FMD as much as regular cigarettes.[9]

Improved FMD results in greater perfusion and oxygen supply to peripheral tissue.[10]

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).[11]

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.[12] The reduction of leg FMD caused by prolonged sitting can be reduced by fidgeting (periodic leg movement).[13]

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.[14]

Forty-five minutes of cycling exercise before sitting has been shown to eliminate the impaired leg FMD due to three hours of sitting.[15] 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.[10]

See also

References
  1. Kelm M (2002). "Flow-mediated dilatation in human circulation: diagnostic and therapeutic aspects". American Journal of Physiology. 282 (1): H1–H5. doi:10.1152/ajpheart.2002.282.1.h1. PMID 11748041.
  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. 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. 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. 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. 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. 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.
  10. 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.
  11. 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.
  12. 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.
  13. 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.
  14. 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.
  15. 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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