Measurement of endothelial function and its clinical utility for cardiovascular risk

Mo Al-Qaisi, Rajesh K Kharbanda, Tarun K Mittal, Ann E Donald, Mo Al-Qaisi, Rajesh K Kharbanda, Tarun K Mittal, Ann E Donald

Abstract

Over the past two decades, the central role of the endothelium in the initiation, progression, and clinical sequelae of atherosclerosis has been increasingly recognized. Assessment of the pathobiology of the endothelium and its ability to act as a potential therapeutic target remains an area of active research interest. Whilst endothelial function has been shown to be a marker for risk of cardiovascular events in high-risk groups, there remains considerable debate about the most appropriate way to assess this. We discuss the different clinical methods to assess endothelial function, focusing on flow-mediated dilatation (FMD) of the brachial artery, highlighting the importance of using a standardized methodology, as well as discussing the clinical limitations of using FMD in individuals.

Keywords: cardiovascular risk; clinical utility; endothelial function; flow-mediated dilatation.

Figures

Figure 1
Figure 1
Probe position in relation to cuff.

References

    1. Agewall S, Doughty RN, Bagg W, et al. Comparison of ultrasound assessment of flow-mediated dilatation in the radial and brachial artery with upper and forearm cuff positions. Clin Physiol. 2001;21:9–14.
    1. Anderson EA, Mark AL. Flow-mediated and reflex changes in large peripheral artery tone in humans. Circulation. 1989;79:93–100.
    1. Anderson TJ. Prognostic significance of brachial flow-mediated vasodilation. Circulation. 2007;115:2373–75.
    1. Berry KL, Skyrme-Jones RA, Meredith IT. Occlusion cuff position is an important determinant of the time course and magnitude of human brachial artery flow-mediated dilation. Clin Sci (Lond) 2000;99:261–7.
    1. Bonetti PO, Pumper GM, Higano ST, et al. Noninvasive identification of patients with early coronary atherosclerosis by assessment of digital reactive hyperemia. J Am Coll Cardiol. 2004;44:2137–41.
    1. Bots M, Westerink J, Rabelink TJ, et al. Assessment of flow-mediated vasodilatation (FMD) of the brachial artery: effects of technical aspects of the FMD measurement on the FMD response. Eur Heart J. 2005;26:363–8.
    1. Celermajer DS, Sorensen KE, Gooch VM, et al. Non-invasive detection of endothelial dysfunction in children and adults at risk of atherosclerosis. Lancet. 1992;340:1111–15.
    1. Celermajer DS, Sorensen KE, Bull C, et al. Endothelium-dependent dilation in the systemic arteries of asymptomatic subjects relates to coronary risk factors and their interaction. J Am Coll Cardiol. 1994;24:1468–74.
    1. Celermajer DS, Ayer JG. Childhood risk factors for adult cardiovascular disease and primary prevention in childhood. Heart. 2006;92:1701–6.
    1. Chong WC, Collins P, Webb CM, et al. Comparison of flow characteristics and vascular reactivity of radial artery and long saphenous vein grafts. J Cardiothorac Surg. 2006;1:4.
    1. Charakida M, Donald AE, Terese M, et al. Endothelial dysfunction in childhood infection. Circulation. 2005;111:1660–5.
    1. Clarkson P, Adams MR, Powe AJ, et al. Oral L-arginine improves endothelium-dependent dilation in hypercholesterolemic young adults. J Clin Invest. 1996;97:1989–94.
    1. Cooke JP, Dzau VJ. Nitric oxide synthase: role in the genesis of vascular disease. Annu Rev Med. 1997;48:489–509.
    1. Corretti MC, Anderson TJ, Benjamin EJ, et al. Guidelines for the ultrasound assessment of endothelial-dependent flow-mediated vasodilation of the brachial artery: a report of the International Brachial Artery Reactivity Task Force. J Am Coll Cardiol. 2002;39:257–65.
    1. Corson MA, James NL, Latta SE, et al. Phosphorylation of endothelial nitric oxide synthase in response to fluid shear stress. Circ Res. 1996;79:984–91.
    1. Deanfield J, Donald A, Ferri C, et al. Endothelial function and dysfunction Part 1: Methodological issues for assessment in the different vascular beds: A statement by the Working Group on Endothelin and Endothelial Factors of the European Society of Hypertension. J Hypertens. 2005;23:7–17.
    1. Deanfield JE, Halcox JP, Rabelink TJ. Endothelial function and dysfunction: testing and clinical relevance. Circulation. 2007;115:1285–95.
    1. Donald AE, Charakida M, Cole TJ, et al. Non-invasive assessment of endothelial function : which technique? J Am Coll Cardiol. 2006;48:1846–50.
    1. Doshi SN, Naka KK, Payne N, et al. Flow-mediated dilatation following wrist and upper arm occlusion in humans: the contribution of nitric oxide. Clin Sci (Lond) 2001;101:629–35.
    1. Duffy SJ, Keaney JF, Holbrook M, et al. Short- and long-term black tea consumption reverses endothelial dysfunction in patients with coronary artery disease. Circulation. 2001;104:151–6.
    1. Ford I, Murray H, Packard CJ, et al. Long-term follow-up of the West of Scotland Coronary Prevention Study. N Engl J Med. 2007;357:1477–86.
    1. Förstermann U, Münzel T. Endothelial nitric oxide synthase in vascular disease: from marvel to menace. Circulation. 2006;113:1708–14.
    1. Furchgott RF, Zawadzki JV. The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature. 1980;288:373–76.
    1. Gokce N, Keaney JF, Hunter LM, et al. Predictive value of non-invasively determined endothelial dysfunction for long-term cardiovascular events in patients with peripheral vascular disease. J Am Coll Cardiol. 2003;41:1769–75.
    1. Guthikonda S, Sinkey CA, Haynes WG. What is the most appropriate methodology for detection of conduit artery endothelial dysfunction? Arterioscler Thromb Vasc Biol. 2007;27:1172–6.
    1. Halcox JP, Schenke WH, Zalos G, et al. Prognostic value of coronary vascular endothelial dysfunction. Circulation. 2002;106:653–8.
    1. Hansell J, Henareh L, Agewall S, et al. Non-invasive assessment of endothelial function – relation between vasodilatory responses in skin microcirculation and brachial artery. Clin Physiol Funct Imaging. 2004;24:317–22.
    1. Hashimoto M, Akishita M, Eto M, et al. Modulation of endothelium-dependent flow-mediated dilatation of the brachial artery by sex and menstrual cycle. Circulation. 1995;92:3431–5.
    1. Herrington DM, Fan L, Drum M, et al. Brachial flow-mediated vasodilator responses in population-based research: methods, reproducibility and effects of age, gender and baseline diameter. J Cardiovasc Risk. 2001;8:319–28.
    1. Hingorani AD, Cross J, Kharbanda RK, et al. Acute systemic inflammation impairs endothelium-dependent dilatation in humans. Circulation. 2000;102:994–9.
    1. Juonala M, Viikari JSA, Laitinen T, et al. Interrelations between brachial endothelial function and carotid intima-media thickness in young adults. The cardiovascular risk in young Finns study. Circulation. 2004;110:2918–23.
    1. Kharbanda RK, Deanfield JE. Functions of the healthy endothelium. Coron Artery Dis. 2001;12:485–91.
    1. Karatzis EN, Ikonomidis I, Vamvakou GD, et al. Long-term prognostic role of flow-mediated dilatation of the brachial artery after acute coronary syndromes without ST elevation. Am J Card. 2006;98:1424–8.
    1. Leeson CPM, Whincup PH, Cook DG, et al. Flow-mediated dilation in 9- to 11-year-old children: the influence of intrauterine and childhood factors. Circulation. 1997;96:2233–8.
    1. Leeson CP, Robinson M, Francis JM, et al. Cardiovascular magnetic resonance imaging for non-invasive assessment of vascular function: validation against ultrasound. J Cardiovasc Magn Reson. 2006;8:381–7.
    1. Matsushima Y, Takase B, Uehata A, et al. Comparative predictive and diagnostic value of flow-mediated vasodilation in the brachial artery and intima media thickness of the carotid artery for assessment of coronary artery disease severity. Int J Cardiol. 2007;117:165–72.
    1. Mullen MJ, Kharbanda RK, Cross J, et al. Heterogeneous nature of flow-mediated dilatation in human conduit arteries in vivo: relevance to endothelial dysfunction in hypercholesterolaemia. Circ Res. 2001;88:145–51.
    1. Nicholls SJ, Sipahi I, Schoenhagen P, et al. Intravascular ultrasound assessment of novel antiatherosclerotic therapies: rationale and design of the Acyl-CoA: Cholesterol Acyltransferase Intravascular Atherosclerosis Treatment Evaluation (ACTIVATE) Study. Am Heart J. 2006;152:67–74.
    1. Palinkas A, Toth E, Venneri L, et al. Temporal heterogeneity of endothelium-dependent and -independent dilatation of brachial artery in patients with coronary artery disease. Int J Cardiovasc Imaging. 2002;18:337–42.
    1. Peretz A, Leotta DF, Sullivan JH, et al. Flow mediated dilation of the brachial artery: an investigation of methods requiring further standardisation. BMC Cardiovasc Disord. 2007;7:11.
    1. Pohl U, Holtz J, Busse R, et al. Crucial role of endothelium in the vasodilator response to increased flow in vivo. Hypertension. 1986;8:37–44.
    1. Reilly JJ, Armstrong J, Dorosty AR, et al. Early life risk factors for obesity in childhood: cohort study. BMJ. 2005;330:1357.
    1. Rubanyi GM, Romero JC, Vanhoutte PM. Flow-induced release of endothelium-derived relaxing factor. Am J Physiol. 1986;250(6 Pt 2):H1145–9.
    1. Sankatsing RR, de Groot E, Jukema JW, et al. Surrogate markers for atherosclerotic disease. Curr Opin Lipidol. 2005;16:434–41.
    1. Schechter AN, Gladwin MT. Haemoglobin and the paracrine and endocrine functions of nitric oxide. N Engl J Med. 2003;384:1483–5.
    1. Shimbo D, Grahame-Clarke C, Miyake Y, et al. The association between endothelial dysfunction and cardiovascular outcomes in a population-based multi-ethnic cohort. Atherosclerosis. 2007;192:197–203.
    1. Smiesko V, Kozik J, Dolezel S. Role of endothelium in the control of arterial diameter by blood flow. Blood Vessels. 1985;22:247–51.
    1. Strain WD, Chaturvedi N, Leggetter S, et al. Ethnic differences in skin microvascular function and their relation to cardiac target-organ damage. J Hypertens. 2005;23:133–40.
    1. Suessenbacher A, Frick M, Alber HF, et al. Association of improvement of brachial artery flow-mediated vasodilation with cardiovascular events. Vasc Med. 2006;11:239–44.
    1. Williams MJ, Sutherland WH, McCormick MP, et al. Impaired endothelial function following a meal rich in used cooking fat. J Am Coll Cardiol. 1999;33:1050–5.
    1. Witte DR, Westerlink J, de Koning EJ, et al. Is the association between flow-mediated dilation and cardiovascular risk limited to low-risk populations? J Am Coll Cardiol. 2005;45:1987–93.
    1. Yeboah J, Crousse JR, Hsu F, et al. Brachial flow-mediated dilation predicts incident cardiovascular events in older adults: The Cardiovascular Health Study. Circulation. 2007;115:2390–97.

Source: PubMed

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