Flow Mediated Dilatation as a Biomarker in Vascular Surgery Research

Kirthi Bellamkonda, Matthew Williams, Ashok Handa, Regent Lee, Kirthi Bellamkonda, Matthew Williams, Ashok Handa, Regent Lee

Abstract

Endothelial dysfunction is one of the hallmarks of atherogenesis, and correlates with many cardiovascular risk factors. One of the features of endothelial dysfunction is the loss of nitric oxide (NO) bioavailability, resulting in derangements in the vasodilatory response of the vessel wall. Flow mediated dilatation (FMD) of the brachial artery is an accepted method for non-invasive assessment of systemic endothelial function. FMD is examined extensively in the context of cardiovascular research, and has been utilised as a routine assessment in large cohorts such as the Framingham Heart Study, Young Finns Study, and Gutenberg Heart Study. However, FMD is less known in the context of vascular surgery research, despite the similarities between the underpinning disease mechanisms. This review will provide a summary of FMD in terms of its history of development and the conduct of the test in research settings. It will further highlight the key literature of FMD as a biomarker for vascular surgeons, particularly in the context of abdominal aortic aneurysms and lower limb peripheral arterial disease.

Keywords: Abdominal aortic aneurysm; Biomarkers; Flow mediated dilatation; Peripheral arterial disease.

Figures

Fig. 1.
Fig. 1.
Graphical illustration of the time course of FMC and FMD

References

    1. Lüscher TF, Barton M: Biology of the endothelium. Clin Cardiol, 1997; 20: II-3-10
    1. Herrmann J, Lerman A: The endothelium: dysfunction and beyond. J Nucl Cardiol, 2001; 8: 197-206
    1. Deanfield JE, Halcox JP, Rabelink TJ: Endothelial Function and Dysfunction. 2007
    1. Flammer AJ, Anderson T, Celermajer DS, Creager MA, Deanfield J, Ganz P, Hamburg NM, Luscher TF, Shechter M, Taddei S, Vita JA, Lerman A: The assessment of endothelial function: from research into clinical practice. Circulation, 2012; 126: 753-767
    1. Alam TA, Seifalian AM, Baker D: A review of methods currently used for assessment of in vivo endothelial function. Eur J Vasc Endovasc Surg, 2005; 29: 269-276
    1. Celermajer DS, Sorensen KE, Gooch VM, Spiegelhalter DJ, Miller OI, Sullivan ID, Lloyd JK, Deanfield JE: Noninvasive detection of endothelial dysfunction in children and adults at risk of atherosclerosis. Lancet, 1992; 340: 1111-1115
    1. Davies PF: Hemodynamic shear stress and the endothelium in cardiovascular pathophysiology. Nat Clin Pract Cardiovasc Med, 2009; 6: 16-26
    1. Ku DN, Giddens DP, Zarins CK, Glagov S: Pulsatile flow and atherosclerosis in the human carotid bifurcation. Positive correlation between plaque location and low oscillating shear stress. Arteriosclerosis, 1985; 5: 293-302
    1. Charakida M, de Groot E, Loukogeorgakis SP, Khan T, Luscher T, Kastelein JJ, Gasser T, Deanfield JE: Variability and reproducibility of flow-mediated dilatation in a multicentre clinical trial. Eur Heart J, 2013; 34: 3501-3507
    1. Greyling A, van Mil AC, Zock PL, Green DJ, Ghiadoni L, Thijssen DH: Adherence to guidelines strongly improves reproducibility of brachial artery flow-mediated dilation. Atherosclerosis, 2016; 248: 196-202
    1. Yagi S, Aihara K, Fukuda D, Takashima A, Hara T, Hotchi J, Ise T, Yamaguchi K, Tobiume T, Iwase T, Yamada H, Soeki T, Wakatsuki T, Shimabukuro M, Akaike M, Sata M: Effects of docosahexaenoic Acid on the endothelial function in patients with coronary artery disease. J Atheroscler Thromb, 2015; 22: 447-454
    1. Ciccone MM, Faienza MF, Altomare M, Nacci C, Montagnani M, Valente F, Cortese F, Gesualdo M, Zito A, Mancarella R, Leogrande D, Viola D, Scicchitano P, Giordano P: Endothelial and Metabolic Function Interactions in Overweight/Obese Children. J Atheroscler Thromb, 2016; 23: 950-959
    1. Benjamin EJ, Larson MG, Keyes MJ, Mitchell GF, Vasan RS, Keaney JF, Jr., Lehman BT, Fan S, Osypiuk E, Vita JA: Clinical correlates and heritability of flow-mediated dilation in the community: the Framingham Heart Study. Circulation, 2004; 109: 613-619
    1. Juonala M, Viikari JS, Laitinen T, Marniemi J, Helenius H, Ronnemaa T, Raitakari OT: Interrelations between brachial endothelial function and carotid intima-media thickness in young adults: the cardiovascular risk in young Finns study. Circulation, 2004; 110: 2918-2923
    1. Schnabel RB, Schulz A, Wild PS, Sinning CR, Wilde S, Eleftheriadis M, Herkenhoff S, Zeller T, Lubos E, Lackner KJ, Warnholtz A, Gori T, Blankenberg S, Munzel T: Noninvasive vascular function measurement in the community: cross-sectional relations and comparison of methods. Circ Cardiovasc Imaging, 2011; 4: 371-380
    1. Ministry of Health, Labour and Welfare: Outline of FY 2012 Revision of Medical Fee. 2017; (in Japanese)
    1. Anderson EA, Mark AL: Flow-mediated and reflex changes in large peripheral artery tone in humans. Circulation, 1989; 79: 93-100
    1. Harris RA, Nishiyama SK, Wray DW, Richardson RS. Ultrasound assessment of flow-mediated dilation. Hypertension, 2010; 55: 1075-1085
    1. Preik M, Lauer T, Heiss C, Tabery S, Strauer BE, Kelm M: Automated ultrasonic measurement of human arteries for the determination of endothelial function. Ultraschall Med, 2000; 21: 195-198
    1. Peretz A, Leotta DF, Sullivan JH, Trenga CA, Sands FN, Aulet MR, Paun M, Gill EA, Kaufman JD: Flow mediated dilation of the brachial artery: an investigation of methods requiring further standardization. BMC Cardiovasc Disord, 2007; 7: 11.
    1. Leeson P, Thorne S, Donald A, Mullen M, Clarkson P, Deanfield J: Non-invasive measurement of endothelial function: effect on brachial artery dilatation of graded endothelial dependent and independent stimuli. Heart, 1997; 78: 22-27
    1. Kajikawa M, Maruhashi T, Hida E, Iwamoto Y, Matsumoto T, Iwamoto A, Oda N, Kishimoto S, Matsui S, Hidaka T, Kihara Y, Chayama K, Goto C, Aibara Y, Nakashima A, Noma K, Higashi Y: Combination of Flow-Mediated Vasodilation and Nitroglycerine-Induced Vasodilation Is More Effective for Prediction of Cardiovascular Events. Hypertension, 2016; 67: 1045-1052
    1. Maruhashi T, Soga J, Fujimura N, Idei N, Mikami S, Iwamoto Y, Kajikawa M, Matsumoto T, Hidaka T, Kihara Y, Chayama K, Noma K, Nakashima A, Goto C, Tomiyama H, Takase B, Yamashina A, Higashi Y: Relationship between flow-mediated vasodilation and cardiovascular risk factors in a large community-based study. Heart, 2013; 99: 1837-1842
    1. Tomiyama H, Kohro T, Higashi Y, Takase B, Suzuki T, Ishizu T, Ueda S, Yamazaki T, Furumoto T, Kario K, Inoue T, Koba S, Watanabe K, Takemoto Y, Hano T, Sata M, Ishibashi Y, Node K, Maemura K, Ohya Y, Furukawa T, Ito H, Ikeda H, Yamashina A: Reliability of measurement of endothelial function across multiple institutions and establishment of reference values in Japanese. Atherosclerosis, 2015; 242: 433-442
    1. Furchgott RF: The 1996 Albert Lasker Medical Research Awards. The discovery of endothelium-derived relaxing factor and its importance in the identification of nitric oxide. Jama, 1996; 276: 1186-1188
    1. Crabtree MJ, Channon KM: Synthesis and recycling of tetrahydrobiopterin in endothelial function and vascular disease. Nitric Oxide, 2011; 25: 81-88
    1. Gori T, Dragoni S, Lisi M, Di Stolfo G, Sonnati S, Fineschi M, Parker JD: Conduit artery constriction mediated by low flow a novel noninvasive method for the assessment of vascular function. J Am Coll Cardiol, 2008; 51: 1953-1958
    1. Gori T, Parker JD, Münzel T: Flow-mediated constriction: further insight into a new measure of vascular function. Eur Heart J, 2011; 32: 784-787
    1. Irace C, Tripolino C, Scavelli FB, Carallo C, Gnasso A: Brachial Low-Flow-Mediated Constriction is Associated with Delayed Brachial Flow-Mediated Dilation. J Atheroscler Thromb, 2016; 23: 355-363
    1. Knipp BS, Peterson DA, Rajagopalan S, Kehrer C, Ford JW, D'Alecy LG, Whitesall SE, Eagleton MJ, Wakefield TW, Henke PK, Jacobs LA, Greenfield LJ, Stanley JC, Upchurch GR, Jr.: Impaired vasoreactivity despite an increase in plasma nitrite in patients with abdominal aortic aneurysms. J Vasc Surg, 2002; 35: 363-367
    1. Gokce N, Keaney JF, Jr., Hunter LM, Watkins MT, Menzoian JO, Vita JA: Risk stratification for postoperative cardiovascular events via noninvasive assessment of endothelial function: a prospective study. Circulation, 2002; 105: 1567-1572
    1. Akamatsu D, Satou A, Watanabe T, Hashizume E, Gotou H, Satomi S: Smooth muscle dysfunction in patients older than 54 years of age with objective evidence of arteriosclerosis. Eur J Vasc Endovasc Surg, 2007; 34: 639-645
    1. Akamatsu D, Sato A, Goto H, Watanabe T, Hashimoto M, Shimizu T, Sugawara H, Sato H, Nakano Y, Miura T, Zukeran T, Serizawa F, Hamada Y, Tsuchida K, Tsuji I, Satomi S: Nitroglycerin-mediated vasodilatation of the brachial artery may predict long-term cardiovascular events irrespective of the presence of atherosclerotic disease. J Atheroscler Thromb, 2010; 17: 1266-1274
    1. Medina F, de Haro J, Florez A, Acin F: Relationship between endothelial dependent vasodilation and size of abdominal aortic aneurysms. Ann Vasc Surg, 2010; 24: 752-757
    1. Sung SH, Wu TC, Chen JS, Chen YH, Huang PH, Lin SJ, Shih CC, Chen JW: Reduced number and impaired function of circulating endothelial progenitor cells in patients with abdominal aortic aneurysm. Int J Cardiol, 2013; 168: 1070-1077
    1. Lee R, Bellamkonda K, Jones A, Killough N, Woodgate F, Williams M, Cassimjee I, Handa A: Flow Mediated Dilatation and Progression of Abdominal Aortic Aneurysms. Eur J Vasc Endovasc Surg, 2017
    1. Loffredo L, Marcoccia A, Pignatelli P, Andreozzi P, Borgia MC, Cangemi R, Chiarotti F, Violi F: Oxidative-stressmediated arterial dysfunction in patients with peripheral arterial disease. Eur Heart J, 2007; 28: 608-612
    1. Loffredo L, Carnevale R, Cangemi R, Angelico F, Augelletti T, Di Santo S, Calabrese CM, Della Volpe L, Pignatelli P, Perri L, Basili S, Violi F: NOX2 up-regulation is associated with artery dysfunction in patients with peripheral artery disease. Int J Cardiol, 2013; 165: 184-192
    1. Maldonado FJ, Miralles Jde H, Aguilar EM, Gonzalez AF, Garcia JR, Garcia FA: Relationship between noninvasively measured endothelial function and peripheral arterial disease. Angiology, 2009; 60: 725-731
    1. Allan RB, Delaney CL,, Miller MD, Spark JI: A comparison of flow-mediated dilatation and peripheral artery tonometry for measurement of endothelial function in healthy individuals and patients with peripheral arterial disease. Eur J Vasc Endovasc Surg, 2013; 45: 263-269
    1. Heinen Y, Stegemann E, Sansone R, Benedens K, Wagstaff R, Balzer J, Rassaf T, Lauer T, Kelm M, Heiss C: Local Association Between Endothelial Dysfunction and Intimal Hyperplasia: Relevance in Peripheral Artery Disease. 2015
    1. Iwamoto A, Kajikawa M, Maruhashi T, Iwamoto Y, Oda N, Kishimoto S, Matsui S, Kihara Y, Chayama K, Goto C, Noma K, Aibara Y, Nakashima A, Higashi Y: Vascular Function and Intima-media Thickness of a Leg Artery in Peripheral Artery Disease: A Comparison of Buerger Disease and Atherosclerotic Peripheral Artery Disease. J Atheroscler Thromb, 2016; 23: 1261-1269
    1. Mancini GB, Hartigan PM, Bates ER, Sedlis SP, Maron DJ, Spertus JA, Berman DS, Kostuk WJ, Shaw LJ, Weintraub WS, Teo KK, Dada M, Chaitman BR, O'Rourke RA, Boden WE: Angiographic disease progression and residual risk of cardiovascular events while on optimal medical therapy: observations from the COURAGE Trial. Circ Cardiovasc Interv, 2011; 4: 545-552
    1. Treasure CB, Klein JL, Weintraub WS, Talley JD, Stillabower ME, Kosinski AS, Zhang J, Boccuzzi SJ, Cedarholm JC, Alexander RW: Beneficial effects of cholesterol-lowering therapy on the coronary endothelium in patients with coronary artery disease. N Engl J Med, 1995; 332: 481-487
    1. Anderson TJ, Meredith IT, Yeung AC, Frei B, Selwyn AP, Ganz P: The effect of cholesterol-lowering and antioxidant therapy on endothelium-dependent coronary vasomotion. N Engl J Med, 1995; 332: 488-493
    1. Mori H, Maeda A, Wakabayashi K, Sato T, Sasai M, Tashiro K, Iso Y, Ebato M, Suzuki H: The Effect of Cilostazol on Endothelial Function as Assessed by Flow-Mediated Dilation in Patients with Coronary Artery Disease. J Atheroscler Thromb, 2016; 23: 1168-1177
    1. Husmann M, Dorffler-Melly J, Kalka C, Diehm N, Baumgartner I, Silvestro A: Successful lower extremity angioplasty improves brachial artery flow-mediated dilation in patients with peripheral arterial disease. J Vasc Surg, 2008; 48: 1211-1216
    1. Unal O, Karatepe O, Ugurlucan M, Koc B, Filizcan U, Aksoy M: Effects of lower extremity revascularization on the endothelial functions measured with noninvasive brachial artery flow-mediated dilatation. Ann Vasc Surg, 2011; 25: 969-974
    1. Jacomella V, Husmann M, Thalhammer C, Uike K, Pfammatter T, Amann-Vesti B: Impact of endovascular treatment of atherosclerotic renal artery stenosis on endothelial function and arterial blood pressure. Int Angiol, 2012; 31: 70-76
    1. Lee R, Bellamkonda K, Jones A, Killough N, Woodgate F, Williams M, Cassimjee I, Handa A: Flow Mediated Dilatation and the Progression of Abdominal Aortic Aneurysms. European Journal of Vascular and Endovascular Surgery, 2017
    1. Weissgerber TL, Davies GA, Tschakovsky ME: Low flow-mediated constriction occurs in the radial but not the brachial artery in healthy pregnant and nonpregnant women. J Appl Physiol (1985), 2010; 108: 1097-1105
    1. Antonopoulos AS, Margaritis M, Lee R, Channon K, Antoniades C: Statins as anti-inflammatory agents in atherogenesis: molecular mechanisms and lessons from the recent clinical trials. Curr Pharm Des, 2012; 18: 1519-1530
    1. Spiro JR, Digby JE, Ghimire G, Mason M, Mitchell AG, Ilsley C, Donald A, Dalby MC, Kharbanda RK: Brachial artery low-flow-mediated constriction is increased early after coronary intervention and reduces during recovery after acute coronary syndrome: characterization of a recently described index of vascular function. Eur Heart J, 2011; 32: 856-866
    1. Norioka N, Takemoto Y, Kobayashi M, Makuuchi A, Yoshikawa J, Yamazaki Y, Kamiyama Y, Shuto T, Yoshiyama M: Low-flow mediated constriction incorporated indices as indicators of cardiovascular risk in smokers. Atherosclerosis, 2016; 251: 132-138

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