Arteriosclerosis, Thrombosis, and Vascular Biology. 2002;22:147-152
doi: 10.1161/hq0102.101770
doi: 10.1161/hq0102.101770
© 2002 American Heart Association, Inc.
Atherosclerosis and Lipoproteins |
Pulse-Wave Analysis
Clinical Evaluation of a Noninvasive, Widely Applicable Method for Assessing Endothelial Function
From the Clinical Pharmacology Units, University of Cambridge (I.B.W., I.S.M., C.M.M.), Addenbrooke’s Hospital, Cambridge, England, and the University of Edinburgh (H.M., B.J.v.d.A., Y.-E.S., L.S.M., D.J.W.), Western General Hospital, Edinburgh, Scotland, and the Department of Cardiology (I.R.H., J.R.C.), University of Wales College of Medicine, University Hospital, Cardiff, Wales.
Correspondence to Dr I.B. Wilkinson, Clinical Pharmacology Unit, University of Cambridge, Addenbrooke’s Hospital, Cambridge CB2 2QQ, UK. E-mail ibw20{at}cam.ac.uk
Currentmethods for assessing vasomotor endothelial function are impractical for use in large studies. We tested the hypothesis that pulse-wave analysis (PWA) combined with provocative pharmacological testing might provide an alternative method. Radial artery waveforms were recorded and augmentation index (AIx) was calculated from derived aortic waveforms. Thirteen subjects received sublingual nitroglycerin (NTG), inhaled albuterol, or placebo. Twelve subjects received NTG, albuterol, and placebo separately during an infusion of NG-monomethyl-L-arginine (LNMMA) or norepinephrine. Twenty-seven hypercholesterolemic subjects and 27 controls received NTG followed by albuterol. Endothelial function was assessed by PWA and forearm blood flow in 27 subjects. Albuterol and NTG both significantly and repeatably reduced AIx (P<0.001). Only the response to albuterol was inhibited by LNMMA (-9.8±5.5% vs -4.7±2.7%; P=0.02). Baseline AIx was higher in the hypercholesterolemic subjects, who exhibited a reduced response to albuterol (P=0.02) but not to NTG when compared with matched controls. The responses to albuterol and acetylcholine were correlated (r=0.5, P=0.02). Consistent with an endothelium-dependent effect, the response to albuterol was substantially inhibited by LNMMA. Importantly, the response to albuterol was reduced in subjects with hypercholesterolemia and was correlated to that of intra-arterial acetylcholine. This methodology provides a simple, repeatable, noninvasive means of assessing endothelial function in vivo.
Key Words: hypercholesterolemia • nitric oxide • pulse-wave analysis • augmentation index • endothelial function
This article has been cited by other articles:
 |
|
 |
|
  M. A. Crilly, V. Kumar, H. J. Clark, N. W. Scott, A. G. MacDonald, and D. J. Williams Arterial stiffness and cumulative inflammatory burden in rheumatoid arthritis: a dose-response relationship independent of established cardiovascular risk factors Rheumatology, October 25, 2009; (2009) kep305v1. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. P. L. Rice, N. Agarwal, H. Bolusani, R. Newcombe, M. F. Scanlon, M. Ludgate, and D. A. Rees Effects of Dehydroepiandrosterone Replacement on Vascular Function in Primary and Secondary Adrenal Insufficiency: A Randomized Crossover Trial J. Clin. Endocrinol. Metab., June 1, 2009; 94(6): 1966 - 1972. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Kohler and J. R. Stradling Cardiovascular Risk in Asymptomatic OSA Am. J. Respir. Crit. Care Med., May 15, 2009; 179(10): 969 - 970. [Full Text] [PDF]
|
|
|
|
 |
|
 M. E. O'Donnell, S. A. Badger, M. A. Sharif, R. R. Makar, I. S. Young, B. Lee, and C.V. Soong The Vascular and Biochemical Effects of Cilostazol in Diabetic Patients With Peripheral Arterial Disease Vascular and Endovascular Surgery, April 1, 2009; 43(2): 132 - 143. [Abstract] [PDF]
|
|
|
|
 |
|
 B. Ilyas, N. Dhaun, D. Markie, P. Stansell, J. Goddard, D.E. Newby, and D.J. Webb Renal function is associated with arterial stiffness and predicts outcome in patients with coronary artery disease QJM, March 1, 2009; 102(3): 183 - 191. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Kohler, S. Craig, D. Nicoll, P. Leeson, R. J. O. Davies, and J. R. Stradling Endothelial Function and Arterial Stiffness in Minimally Symptomatic Obstructive Sleep Apnea Am. J. Respir. Crit. Care Med., November 1, 2008; 178(9): 984 - 988. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N L Mills, J J Miller, A Anand, S D Robinson, G A Frazer, D Anderson, L Breen, I B Wilkinson, C M McEniery, K Donaldson, et al. Increased arterial stiffness in patients with chronic obstructive pulmonary disease: a mechanism for increased cardiovascular risk Thorax, April 1, 2008; 63(4): 306 - 311. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. E. Sharman, C. M. McEniery, R. Campbell, P. Pusalkar, I. B. Wilkinson, J. S. Coombes, and J. R. Cockcroft Nitric Oxide Does Not Significantly Contribute to Changes in Pulse Pressure Amplification During Light Aerobic Exercise Hypertension, April 1, 2008; 51(4): 856 - 861. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Frimodt-Moller, A. H. Nielsen, A.-L. Kamper, and S. Strandgaard Reproducibility of pulse-wave analysis and pulse-wave velocity determination in chronic kidney disease Nephrol. Dial. Transplant., February 1, 2008; 23(2): 594 - 600. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Munir, A. Guilcher, T. Kamalesh, B. Clapp, S. Redwood, M. Marber, and P. Chowienczyk Peripheral Augmentation Index Defines the Relationship Between Central and Peripheral Pulse Pressure Hypertension, January 1, 2008; 51(1): 112 - 118. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Crilly, C. Coch, M. Bruce, H. Clark, and D. Williams Indices of cardiovascular function derived from peripheral pulse wave analysis using radial applanation tonometry: a measurement repeatability study Vascular Medicine, August 1, 2007; 12(3): 189 - 197. [Abstract] [PDF]
|
|
|
|
|
|
A. Barac, U. Campia, and J. A. Panza Methods for Evaluating Endothelial Function in Humans Hypertension, April 1, 2007; 49(4): 748 - 760. [Full Text] [PDF]
|
|
|
|
 |
|
 J. E. Deanfield, J. P. Halcox, and T. J. Rabelink Endothelial Function and Dysfunction: Testing and Clinical Relevance Circulation, March 13, 2007; 115(10): 1285 - 1295. [Full Text] [PDF]
|
|
|
|
 |
|
 A. E. Donald, M. Charakida, T. J. Cole, P. Friberg, P. J. Chowienczyk, S. C. Millasseau, J. E. Deanfield, and J. P. Halcox Non-Invasive Assessment of Endothelial Function: Which Technique? J. Am. Coll. Cardiol., November 7, 2006; 48(9): 1846 - 1850. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. M. McEniery, S. Wallace, I. S. Mackenzie, B. McDonnell, Yasmin, D. E. Newby, J. R. Cockcroft, and I. B. Wilkinson Endothelial Function Is Associated With Pulse Pressure, Pulse Wave Velocity, and Augmentation Index in Healthy Humans Hypertension, October 1, 2006; 48(4): 602 - 608. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Verdecchia, F. Angeli, and S. Taddei At the Beginning of Stiffening: Endothelial Dysfunction Meets "Pulsology" Hypertension, October 1, 2006; 48(4): 541 - 542. [Full Text] [PDF]
|
|
|
|
 |
|
 H. Sourij, R. Zweiker, and T. C. Wascher Effects of Pioglitazone on Endothelial Function, Insulin Sensitivity, and Glucose Control in Subjects With Coronary Artery Disease and New-Onset Type 2 Diabetes Diabetes Care, May 1, 2006; 29(5): 1039 - 1045. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. K. Naka, A. C. Tweddel, S. N. Doshi, J. Goodfellow, and A. H. Henderson Flow-mediated changes in pulse wave velocity: a new clinical measure of endothelial function Eur. Heart J., February 1, 2006; 27(3): 302 - 309. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Weber, J. Auer, M. F. O'Rourke, E. Kvas, E. Lassnig, G. Lamm, N. Stark, M. Rammer, and B. Eber Increased arterial wave reflections predict severe cardiovascular events in patients undergoing percutaneous coronary interventions Eur. Heart J., December 2, 2005; 26(24): 2657 - 2663. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Nair, R. K Oka, L. D Waring, E. M Umoh, C B. Taylor, and J. P Cooke Vascular compliance versus flow-mediated vasodilation: correlation with cardiovascular risk factors Vascular Medicine, November 1, 2005; 10(4): 275 - 283. [Abstract] [PDF]
|
|
|
|
 |
|
 L. Kalra, C. Rambaran, P. Chowienczyk, D. Goss, I. Hambleton, J. Ritter, A. Shah, R. Wilks, and T. Forrester Ethnic Differences in Arterial Responses and Inflammatory Markers in Afro-Caribbean and Caucasian Subjects Arterioscler Thromb Vasc Biol, November 1, 2005; 25(11): 2362 - 2367. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Lind, N. Fors, J. Hall, K. Marttala, and A. Stenborg A Comparison of Three Different Methods to Evaluate Endothelium-Dependent Vasodilation in the Elderly: The Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) Study Arterioscler Thromb Vasc Biol, November 1, 2005; 25(11): 2368 - 2375. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Verbeke, P. Segers, S. Heireman, R. Vanholder, P. Verdonck, and L. M. Van Bortel Noninvasive Assessment of Local Pulse Pressure: Importance of Brachial-to-Radial Pressure Amplification Hypertension, July 1, 2005; 46(1): 244 - 248. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Swampillai, S. Doshi, A. G Fraser, J. Goodfellow, and C. J. Jones Review: Clinical assessment of endothelial function -- an update The British Journal of Diabetes & Vascular Disease, March 1, 2005; 5(2): 72 - 76. [Abstract] [PDF]
|
|
|
|
|
|
G. S. Stokes, A. J Bune, N. Huon, and E. S. Barin Long-Term Effectiveness of Extended-Release Nitrate for the Treatment of Systolic Hypertension Hypertension, March 1, 2005; 45(3): 380 - 384. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. A. Hope, D. B. Tay, I. T. Meredith, and J. D. Cameron Use of Arterial Transfer Functions for the Derivation of Central Aortic Waveform Characteristics in Subjects With Type 2 Diabetes and Cardiovascular Disease: Response to Wilkinson and McEniery and Avolio, Cockcroft, and O'Rourke Diabetes Care, October 1, 2004; 27(10): 2565 - 2567. [Full Text] [PDF]
|
|
|
|
|
|
M. F. O'Rourke and W. W. Nichols Shear Stress and Flow-Mediated Dilation Hypertension, August 1, 2004; 44(2): 119 - 120. [Full Text] [PDF]
|
|
|
|
|
|
I. B. Wilkinson, S. S. Franklin, and J. R. Cockcroft Nitric Oxide and the Regulation of Large Artery Stiffness: From Physiology to Pharmacology Hypertension, August 1, 2004; 44(2): 112 - 116. [Full Text] [PDF]
|
|
|
|
|
|
A. Covic, D. J. A. Goldsmith, P. Gusbeth-Tatomir, and M. Covic Haemodialysis acutely improves endothelium-independent vasomotor function without significantly influencing the endothelium-mediated abnormal response to a {beta}2-agonist Nephrol. Dial. Transplant., March 1, 2004; 19(3): 637 - 643. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Mather and R. Lewanczuk Measurement of Arterial Stiffness in Diabetes: A cautionary tale Diabetes Care, March 1, 2004; 27(3): 831 - 833. [Full Text] [PDF]
|
|
|
|
 |
|
 D. K. Plante and J. L. Nadler Diabetes and Vascular Disease Seminars in Cardiothoracic and Vascular Anesthesia, September 1, 2003; 7(3): 295 - 310. [Abstract] [PDF]
|
|
|
|
|
|
J. J. Oliver and D. J. Webb Noninvasive Assessment of Arterial Stiffness and Risk of Atherosclerotic Events Arterioscler Thromb Vasc Biol, April 1, 2003; 23(4): 554 - 566. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. S. Stokes, E. S. Barin, and K. L. Gilfillan Effects of Isosorbide Mononitrate and AII Inhibition on Pulse Wave Reflection in Hypertension Hypertension, February 1, 2003; 41(2): 297 - 301. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. L.M. Cruden, D. E. Newby, D. J. Webb, P. Bartsch, H. Mairbaurl, B. Basnyat, P. Prodhan, N. N. Noviski, T. B. Kinane, E. R. Swenson, et al. Salmeterol for the Prevention of High-Altitude Pulmonary Edema N. Engl. J. Med., October 17, 2002; 347(16): 1282 - 1285. [Full Text] [PDF]
|
|