Endothelial dysfunction precedes clinically detectable vascular disease, suggesting its early detection may allow the targeting of treatment to improve endothelial function and thus inhibit progression of disease.1,2 Although the evidence for a preventive strategy remains circumstantial, there is worldwide interest in the measurement of endothelial function in relation to risk factors and treatment of atherosclerotic vascular disease. Unfortunately, a widely applicable clinical measurement of endothelial function does not yet exist; those that are available remain tools for research. The ideal clinical test of endothelial function should be specific, sensitive and reproducible, as well as simple to perform, painless, and inexpensive. In this review we outline the relative merits and disadvantages of the techniques that are available.
Mano T., Masuyama T., Yamamoto K. et al. Endothelial dysfunction in the early stage of atherosclerosis precedes appearance of intimal lesions assessable with intravascular ultrasound . Am Heart J1996;131:231-8.
2.
Reddy KG, Nair RN, Sheehan HM, Hodgson JMEvidence that selective endothelial dysfunction may occur in the absence of angiographic or ultrasound atherosclerosis in patients with risk factors for atherosclerosis. J Am Coll Cardiol1994 ;23:833-43.
3.
Lip GY, BlannA . von Willebrand factor: a marker of endothelial dysfunction in vascular disorders?Cardiovasc Res1997;34:255-65.
4.
Conway DSG , Pearce LA, Chin BSP , Hart RG, Lip GYH.Prognostic value of plasma von Willebrand factor and soluble P-Selectin as indices of endothelial damage and platelet activation in 994 patients with non-valvular atrial fibrillation. Circ2003 ;107:3141-5.
5.
Mezaki T., Matsubara T., Hori T. et al. Plasma levels of soluble thrombomodulin, C-reactive protein, and serum amyloid A protein in the atherosclerotic coronary circulation. Jpn Heart J2003;44:601-12.
6.
Blann AD, Amiral J., McCollum CNPrognostic value of increased soluble thrombomodulin and increased soluble E-selectin in ischaemic heart disease. Eur J Haematol1997;59:115-20.
7.
Cai H., Harrison DGEndothelial dysfunction in cardiovascular diseases: The role of oxidant stress . Circ Res2000;87:840-4.
8.
Baylis C., Vallance P.Measurement of nitrite and nitrate levels in plasma and urine - what does this measure tell us about the activity of the endogenous nitric oxide system?Curr Opin Nephrol Hypertens1998;7:59-62.
9.
Zeballos GA, Bernstein RD, Thompson CI et al. Pharmacodynamics of plasma nitrate/nitrite as an indication of nitric oxide formation in conscious dogs. Circ1995;91:2982-8.
10.
Simak J., Holada K., Risitano AM, Zivny JH, Young NS, Vostal JGElevated circulating endothelial membrane microparticles in paroxysmal nocturnal haemoglobinuria. Br J Haematol2004 ;125:804-13.
11.
Boulanger CM , Scoazec A., Ebrahimian T. et al. Circulating microparticles from patients with myocardial infarction cause endothelial dysfunction. Circ2001;104:2649-52.
12.
Nomura S., Suzuki M., Katsura K. et al. Platelet-derived microparticles may influence the development of atherosclerosis in diabetes mellitus. Atherosclerosis1995;116:235-40.
13.
Preston RA, Jy W., Jimenez JJ et al. Effects of severe hypertension on endothelial and platelet microparticles . Hypertens2003;41:211-17.
14.
Brodsky SV, Zhang F., Nasjletti A., Goligorsky MSEndothelium-derived microparticles impair endothelial function in vitro. Am J Physiol Heart Circ Physiol2004 ;286:H1910-H1915.
15.
Berghoff M. , Kathpal M., Kilo S., Hilz MJ, Freeman R.Vascular and neural mechanisms of ACh-mediated vasodilation in the forearm cutaneous microcirculation . J Appl Physiol2002;92:780-8.
16.
Newton DJ, Khan F., Belch JJF.Assessment of microvascular endothelial function in human skin. Clin Sci2001;101:567-72.
17.
Hewlett AW, van Zwaluwenburg JGThe rate of blood flow in the arm. Heart1909 ;1:87-97.
18.
Whitney RJThe measurement of volume changes in human limbs. J Physiol1953;121:1-27.
19.
Lind L., Sarabi M., Millgard J.Methodological aspects of the evaluation of endothelium-dependent vasodilatation in the human forearm. Clin Physiol1998;18:81-7.
20.
Cooper KE, Edholm OG, Mottram RFThe blood flow in skin and muscle of the human forearm. J Physiol1955;128:258-67.
21.
Roddie IC, Wallace WFM.Methods for the assessment of the effects of drugs on the arterial system in man. Br J Clin Pharmacol1979;7:317-23.
22.
Endo T., Imaizumi T., Tagawa T., Shiramoto M., Ando S., Takeshita A.Role of nitric oxide in exercise-induced vasodilation of the forearm. Circ1994;90:2886-90.
23.
Meredith IT , Currie KE, Anderson TJ, Roddy MA, Ganz P., Creager MAPostischemic vasodilation in human forearm is dependent on endothelium-derived nitric oxide . Am J Physiol1996;270:H1435-40.
24.
McVeigh GE, Brennan GM, Johnston GD et al. Impaired endotheliumdependent and independent vasodilation in patients with type 2 (non-insulin-dependent) diabetes mellitus. Diabetologia1992;35:771-6.
25.
Creager MA, Cooke JP, Mendelsohn ME et al. Impaired vasodilation of forearm resistance vessels in hypercholesterolemic humans. J Clin Invest1990;86:228-34.
26.
Panza JA, Epstein SE, Quyyumi AACircadian variation in vascular tone and its relation to alpha-sympathetic vasoconstrictor activity. N Engl J Med1991 ;325:986-90.
27.
Roberts DH, Tsao Y., Breckenridge AMThe reproducibility of limb blood flow measurements in human volunteers at rest and after exercise by using mercury-in-silastic strain gauge plethysmography under standardised conditions. Clin Sci1986 ;70:635-8.
Lind L., Hall J., Larsson A., Annuk M., Fellström B., Lithell H.Evaluation of endothelium-dependent vasodilation in the human peripheral circulation . Clin Physio2000;20:440-8.
30.
Chowienczyk PJ, Cockcroft JR, Ritter JMBlood flow responses to intraarterial acetylcholine in man: effects of basal flow and conduit vessel length. Clin Sci (Lond) 1994;87(1):45-51.
31.
Garland JG, McPherson GAEvidence that nitric oxide does not mediate the hyperpolarization and relaxation to acetylcholine in the rat small mesenteric artery. Br J Pharmacol1992;105:429-35.
32.
Junstad M., Wennmalm A.Release of prostaglandin from the rabbit isolated heart following vagal nerve stimulation or acetylcholine infusion. Br J Pharmacol1974;52:375-9.
33.
Schmitt M., Blackman DJ, Middleton GW, Cockcroft JRAssessment of venous capacitance. Radionuclide plethysmography: methodology and research applications. Br J Clin Pharmacol2002;54:565-76.
34.
Scott-Douglas NW, Manyari DE, Smiseth OA et al. Measurement of intestinal vascular capacitance in dogs: an application of blood pool scintigraphy . J Appl Physiol1995;78:232-8.
35.
Thomson HL, Morris-Thurgood J., Atherton J., McKenna W., Frenneaux MPReflex responses of venous capacitance vessels in patients with hypertrophic cardiomyopathy. Clin Sci1998;94:339-46.
36.
Atherton JJ , Dryburgh LG, Thomson HL et al. Forearm vasoconstriction during dynamic leg exercise in patients with chronic heart failure. Heart Vessels1998;13:278-89.
37.
Celermajer DS, Sorensen KE, Gooch VM et al. Non-invasive detection of endothelial dysfunction in children and adults at risk of atherosclerosis . Lancet1992;340:1111-15.
38.
Stadler RW, Taylor JA, Lees RSComparison of B-mode, M-mode and echo-tracking methods for measurement of the arterial distension waveform. Ultrasound Med Biol1997;23:879-87.
39.
Sorensen KE , Celermajer DS, Spiegelhalter DJ et al. Non-invasive measurement of human endothelium dependent arterial responses: accuracy and reproducibility. Br Heart J1995;74:247-53.
40.
Hardie KL, Kinlay S., Hardy DB, Wlodarczyk J., Silberberg JS, Fletcher PJReproducibility of brachial ultrasonography and flow-mediated dilatation (FMD) for assessing endothelial function. Aust N Z J Med1997;27:649-52.
41.
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.
42.
Davies JI, Struthers ADPulse wave analysis and pulse wave velocity: a critical review of their strengths and weaknesses. J Hypertension2003; 21:463-72.
43.
Millasseau SC, Kelly RP, Ritter JM, Chowienczyk PJDetermination of age-related increase in large artery stiffness by digital pulse contour analysis. Clin Sci2002;103:371-7.
44.
Ramsey MW, Goodfellow J., Jones CJH, Luddington LA, Lewis MJ, Henderson AHEndothelial control of arterial distensibility is impaired in chronic heart failure. Circ1995;92:3212-19.
45.
Naka KK, Tweddel AC, Parthimos D., Henderson A., Goodfellow J., Frenneaux MPArterial distensibility: acute changes following dynamic exercise in normal subjects. Am J Physiol Heart Circ Physiol2003;284:H970-8.
46.
Yamashina A. , Tomiyama H., Takeda K. et al. Validity, reproducibility, and clinical significance of noninvasive brachial-ankle pulse wave velocity measurement . Hypertens Res2002;25:359-64.
47.
Wilkinson IB , MacCallum H., Rooijmans DF et al. Increased augmentation index and systolic stress in Type 1 diabetes mellitus. Q J Med2000; 93:441-8.
48.
London GM, Blacher J., Pannier B., Guerin AP, Marchais SJ, Safar MEArterial wave reflections and survival in end-stage renal failure . Hypertens2001;38:434-8.
49.
Wilkinson IB , Hall IR, MacCallum H. et al. Pulse wave analysis: Clinical evaluation of a non-invasive widely applicable method for assessing endothelial function . Arterioscler Thromb Vasc Biol2002 ;22:147-52.
50.
Wilkinson IB , Fuchs SA, Jansen IM et al. Reproducibility of pulse wave velocity and augmentation index measured by pulse wave analysis . J Hypertens1999;16:2079-84.
51.
Dawes M., Chowienczyk PJ, Ritter JMEffects of inhibition of the L-arginine/nitric oxide pathway on vasodilation caused by ß-adrenergic agonists in human forearm. Circ1997;95:2293-7.
52.
Wilkinson IB , MacCallum H., Flint L., Cockcroft JR, Newby DE, Webb DJThe influence of heart rate on augmentation index and central arterial pressure in humans. J Physiol2000;525:263-70.
53.
McGrath BP, Liang Y.-L, Kotsopoulos D., Cameron JDImpact of physical and physiological factors on arterial function . Clin Exp Pharmacol Physiol2001;28:1104-07.
54.
Kelly RP, Millasseau SC, Ritter JM, Chowienczyk PJVasoactive drugs influence aortic augmentation index independently of pulse wave velocity in healthy men. Hypertens2001 ;37:1429-33.
55.
McVeigh GE, Bratteli CW, Morgan DJ et al. Age-related abnormalities in arterial compliance identified by pressure pulse contour analysis: Aging and arterial compliance. Hypertens1999;33:1392-8.
56.
R. Kelly, C. Hayward, A.Avolio, M.O'Rourke.Noninvasive determination of age-related changes in the human arterial pulse . Circ1989;80:1652-9.
