Review: Clinical assessment of endothelial function

Abstract

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.

Keywords

endothelial function conduit arteries arterial stiffness endothelial activation.

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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 J 1996;131:231-8.

Reddy KG , Nair RN , Sheehan HM , Hodgson JM Evidence that selective endothelial dysfunction may occur in the absence of angiographic or ultrasound atherosclerosis in patients with risk factors for atherosclerosis. J Am Coll Cardiol 1994 ;23:833-43.

Lip GY , BlannA . von Willebrand factor: a marker of endothelial dysfunction in vascular disorders? Cardiovasc Res 1997;34:255-65.

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. Circ 2003 ;107:3141-5.

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 J 2003;44:601-12.

Blann AD , Amiral J. , McCollum CN Prognostic value of increased soluble thrombomodulin and increased soluble E-selectin in ischaemic heart disease. Eur J Haematol 1997;59:115-20.

Cai H. , Harrison DG Endothelial dysfunction in cardiovascular diseases: The role of oxidant stress . Circ Res 2000;87:840-4.

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 Hypertens 1998;7:59-62.

Zeballos GA , Bernstein RD , Thompson CI et al. Pharmacodynamics of plasma nitrate/nitrite as an indication of nitric oxide formation in conscious dogs. Circ 1995;91:2982-8.

10.

Simak J. , Holada K. , Risitano AM , Zivny JH , Young NS , Vostal JG Elevated circulating endothelial membrane microparticles in paroxysmal nocturnal haemoglobinuria. Br J Haematol 2004 ;125:804-13.

11.

Boulanger CM , Scoazec A. , Ebrahimian T. et al. Circulating microparticles from patients with myocardial infarction cause endothelial dysfunction. Circ 2001;104:2649-52.

12.

Nomura S. , Suzuki M. , Katsura K. et al. Platelet-derived microparticles may influence the development of atherosclerosis in diabetes mellitus. Atherosclerosis 1995;116:235-40.

13.

Preston RA , Jy W. , Jimenez JJ et al. Effects of severe hypertension on endothelial and platelet microparticles . Hypertens 2003;41:211-17.

14.

Brodsky SV , Zhang F. , Nasjletti A. , Goligorsky MS Endothelium-derived microparticles impair endothelial function in vitro. Am J Physiol Heart Circ Physiol 2004 ;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 Physiol 2002;92:780-8.

16.

Newton DJ , Khan F. , Belch JJF. Assessment of microvascular endothelial function in human skin. Clin Sci 2001;101:567-72.

17.

Hewlett AW , van Zwaluwenburg JG The rate of blood flow in the arm. Heart 1909 ;1:87-97.

18.

Whitney RJ The measurement of volume changes in human limbs. J Physiol 1953;121:1-27.

19.

Lind L. , Sarabi M. , Millgard J. Methodological aspects of the evaluation of endothelium-dependent vasodilatation in the human forearm. Clin Physiol 1998;18:81-7.

20.

Cooper KE , Edholm OG , Mottram RF The blood flow in skin and muscle of the human forearm. J Physiol 1955;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 Pharmacol 1979;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. Circ 1994;90:2886-90.

23.

Meredith IT , Currie KE , Anderson TJ , Roddy MA , Ganz P. , Creager MA Postischemic vasodilation in human forearm is dependent on endothelium-derived nitric oxide . Am J Physiol 1996;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. Diabetologia 1992;35:771-6.

25.

Creager MA , Cooke JP , Mendelsohn ME et al. Impaired vasodilation of forearm resistance vessels in hypercholesterolemic humans. J Clin Invest 1990;86:228-34.

26.

Panza JA , Epstein SE , Quyyumi AA Circadian variation in vascular tone and its relation to alpha-sympathetic vasoconstrictor activity. N Engl J Med 1991 ;325:986-90.

27.

Roberts DH , Tsao Y. , Breckenridge AM The 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 Sci 1986 ;70:635-8.

28.

Petrie JR , Ueda S. , Morris AD , Murray LS , Elliott HL , Connell JM

How reproducible is bilateral forearm plethysmography?

Br J Clin Pharmacol 1998;45:131-9.

29.

Lind L. , Hall J. , Larsson A. , Annuk M. , Fellström B. , Lithell H. Evaluation of endothelium-dependent vasodilation in the human peripheral circulation . Clin Physio 2000;20:440-8.

30.

Chowienczyk PJ , Cockcroft JR , Ritter JM Blood 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 GA Evidence that nitric oxide does not mediate the hyperpolarization and relaxation to acetylcholine in the rat small mesenteric artery. Br J Pharmacol 1992;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 Pharmacol 1974;52:375-9.

33.

Schmitt M. , Blackman DJ , Middleton GW , Cockcroft JR Assessment of venous capacitance. Radionuclide plethysmography: methodology and research applications. Br J Clin Pharmacol 2002;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 Physiol 1995;78:232-8.

35.

Thomson HL , Morris-Thurgood J. , Atherton J. , McKenna W. , Frenneaux MP Reflex responses of venous capacitance vessels in patients with hypertrophic cardiomyopathy. Clin Sci 1998;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 Vessels 1998;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 . Lancet 1992;340:1111-15.

38.

Stadler RW , Taylor JA , Lees RS Comparison of B-mode, M-mode and echo-tracking methods for measurement of the arterial distension waveform. Ultrasound Med Biol 1997;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 J 1995;74:247-53.

40.

Hardie KL , Kinlay S. , Hardy DB , Wlodarczyk J. , Silberberg JS , Fletcher PJ Reproducibility of brachial ultrasonography and flow-mediated dilatation (FMD) for assessing endothelial function. Aust N Z J Med 1997;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 AD Pulse wave analysis and pulse wave velocity: a critical review of their strengths and weaknesses. J Hypertension 2003; 21:463-72.

43.

Millasseau SC , Kelly RP , Ritter JM , Chowienczyk PJ Determination of age-related increase in large artery stiffness by digital pulse contour analysis. Clin Sci 2002;103:371-7.

44.

Ramsey MW , Goodfellow J. , Jones CJH , Luddington LA , Lewis MJ , Henderson AH Endothelial control of arterial distensibility is impaired in chronic heart failure. Circ 1995;92:3212-19.

45.

Naka KK , Tweddel AC , Parthimos D. , Henderson A. , Goodfellow J. , Frenneaux MP Arterial distensibility: acute changes following dynamic exercise in normal subjects. Am J Physiol Heart Circ Physiol 2003;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 Res 2002;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 Med 2000; 93:441-8.

48.

London GM , Blacher J. , Pannier B. , Guerin AP , Marchais SJ , Safar ME Arterial wave reflections and survival in end-stage renal failure . Hypertens 2001;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 Biol 2002 ;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 Hypertens 1999;16:2079-84.

51.

Dawes M. , Chowienczyk PJ , Ritter JM Effects of inhibition of the L-arginine/nitric oxide pathway on vasodilation caused by ß-adrenergic agonists in human forearm. Circ 1997;95:2293-7.

52.

Wilkinson IB , MacCallum H. , Flint L. , Cockcroft JR , Newby DE , Webb DJ The influence of heart rate on augmentation index and central arterial pressure in humans. J Physiol 2000;525:263-70.

53.

McGrath BP , Liang Y. -L, Kotsopoulos D. , Cameron JD Impact of physical and physiological factors on arterial function . Clin Exp Pharmacol Physiol 2001;28:1104-07.

54.

Kelly RP , Millasseau SC , Ritter JM , Chowienczyk PJ Vasoactive drugs influence aortic augmentation index independently of pulse wave velocity in healthy men. Hypertens 2001 ;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. Hypertens 1999;33:1392-8.

56.

R. Kelly , C. Hayward , A.Avolio , M.O'Rourke. Noninvasive determination of age-related changes in the human arterial pulse . Circ 1989;80:1652-9.

Review: Clinical assessment of endothelial function — an update

Abstract

Keywords

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