Cited by 2,033Cardiovascular Health and Disease PreventionNitric Oxide and Endothelin EffectsCardiovascular Function and Risk Factors

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Close relation of endothelial function in the human coronary and peripheral circulations

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Anderson, Todd J., Uehata, Akimi, Gerhard, Marie D., Meredith, Ian T., Knab, Sarah, Delagrange, Danielle, Lieberman, Eric H., Ganz, Peter, Creager, Mark A., Yeung, Alan C., Selwyn, Andrew P.·1995·Journal of the American College of Cardiology

DOI 10.1016/0735-1097(95)00327-4

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Abstract

Objectives The relation between endothelium-dependent vasodilator function in the brachial and coronary arteries was determined in the same subjects.Background Coronary artery endothelial dysfunction precedes the development of overt atherosclerosis and is important in its pathogenesis. A noninvasive assessment of endothelial function in a peripheral conduit vessel, the brachial artery, was recently described, but the relation between brachial artery function and coronary artery vasodilator function has not been explored.Methods In 50 patients referred to the catheterization laboratory for the evaluation of coronary artery disease (mean age +/- SD 56 +/- 10 years), the coronary vasomotor response to serial intracoronary infusions of the endothelium-dependent agonist acetylcholine (10(-8) to 10(-6) mol/liter), was studied. Endothelium-dependent vasodilation was also assessed in the brachial artery by measuring the change in brachial artery diameter in response to reactive hyperemia.Results Patients with coronary artery endothelial dysfunction manifested as vasoconstriction in response to acetylcholine had significantly impaired flow-mediated vasodilation in the brachial artery compared with that of patients with normal coronary endothelial function (4.8 +/- 5.5% vs. 10.8 +/- 7.6%, p < 0.01). Patients with coronary artery disease also had an attenuated brachial artery vasodilator response compared with that of patients with angiographically smooth coronary arteries (4.5 +/- 4.6% vs. 9.7 +/- 8.1%, p < 0.02). By multivariate analysis, the strongest predictors of reduced brachial dilator responses to flow were baseline brachial artery diameter (p < 0.001), coronary endothelial dysfunction (p = 0.003), the presence of coronary artery disease (p = 0.007) and cigarette smoking (p = 0.016). The brachial artery vasodilator response to sublingual nitroglycerin was independent of coronary endothelial responses or the presence of coronary artery disease. The positive predictive value of abnormal brachial dilation ( < 3%) in predicting coronary endothelial dysfunction is 95%.Conclusions This study demonstrated a close relation between coronary artery endothelium-dependent vasomotor responses to acetylcholine and flow-mediated vasodilation in the brachial artery. This noninvasive method may become a useful surrogate in assessing the predisposition to atherosclerosis in patients with cardiac risk factors.

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Method
Physical Exercise Protects Against Endothelial Dysfunction in Cardiovascular and Metabolic Diseases
Gao, J., Pan, X., Li, G., Chatterjee, E., & Xiao, J. (2021) · Journal of Cardiovascular Translational Research · doi:10.1007/s12265-021-10171-3 · Cited by 84
The association between microvascular and macrovascular endothelial function in patients with rheumatoid arthritis: a cross-sectional study
Sandoo, A., Carroll, D., Metsios, G. S., Kitas, G. D., & Zanten, J. V. (2011) · Arthritis Research & Therapy · doi:10.1186/ar3374 · Cited by 81
“These assessments are reflective of coronary endothelial function [8-11] and have been shown to be good predictors of long-term cardiovascular events in individuals with atherosclerosis [12-15] and peripheral vascular disease [16], as well as in healthy older participants [17].”
Background
Cardiovascular disease in HIV-positive patients
Kamin, D., & Grinspoon, S. K. (2005) · AIDS · doi:10.1097/01.aids.0000166087.08822.bc · Cited by 80
Impaired Coronary Endothelium-Dependent Vasodilation Is Associated With Microalbuminuria in Patients With Type 2 Diabetes and Angiographically Normal Coronary Arteries
Cosson, E., Pham, I., Valensi, P. E., Pariès, J., Attali, J. R., & Nitenberg, A. (2006) · Diabetes Care · doi:10.2337/diacare.29.01.06.dc05-1422 · Cited by 81
“36, n 50) with abnormal vasomotor responses of the coronary circulation (18).”
Background
Assessment and Prognosis of Peripheral Artery Measures of Vascular Function
Anderson, T. J., & Phillips, S. A. (2014) · Progress in Cardiovascular Diseases · doi:10.1016/j.pcad.2014.11.005 · Cited by 80
Non-Invasive Diagnostic Tools for Investigating Endothelial Dysfunction
Ghiadoni, L., Versari, D., Giannarelli, C., Faita, F., & Taddei, S. (2008) · Current Pharmaceutical Design · doi:10.2174/138161208786898761 · Cited by 78
Vascular Endothelial Function and Leisure-Time Physical Activity in Adolescents
Pahkala, K., Heinonen, O. J., Lagström, H., Hakala, P., Simell, O., Viikari, J. S. A., Rönnemaa, T., Hernelahti, M., Sillanmäki, L. H., & Raitakari, O. T. (2008) · Circulation · doi:10.1161/circulationaha.108.791988 · Cited by 80
Folate and Vitamin B6 Rapidly Normalize Endothelial Dysfunction In Children With Type 1 Diabetes Mellitus
MacKenzie, K. E., Wiltshire, E. J., Gent, R. J., Hirte, C., Piotto, L., & Couper, J. (2006) · PEDIATRICS · doi:10.1542/peds.2005-2143 · Cited by 80
Endothelial Functions Improve with Decrease in Asymmetric Dimethylarginine (ADMA) Levels after Renal Transplantation
Yılmaz, M. İ., Sağlam, M., Çağlar, K., Çakır, E., Özgürtaş, T., Sönmez, A., Eyileten, T., Yenicesu, M., Açıkel, C., Oğuz, Y., et al. (2005) · Transplantation · doi:10.1097/01.tp.0000183750.22675.be · Cited by 79
“Endothelial dysfunction (ED), the impairment of regulatory functions of endothelium for vasodilatation, smooth muscle cell proliferation and fibrinolysis, plays a pivotal role in the pathogenesis of cardiovascular events (1, 2).”
Background
Effect of Enalapril on Endothelial Function in Young Insulin-Dependent Diabetic Patients: A Randomized, Double-Blind Study 11This study was supported by a grant from Merck Sharp and Dohme Ltd., Hertfordshire, England, United Kingdom. Ms. Donald is supported by a grant from the Coronary Artery Disease Research Foundation (CORDA), London, England, United Kingdom.
Mullen, M. J., Clarkson, P., Donald, A. E., Thomson, H., Thorne, S., Powe, A. J., Furuno, T., Bull, T., & Deanfield, J. E. (1998) · Journal of the American College of Cardiology · doi:10.1016/s0735-1097(98)00099-0 · Cited by 80
“blocked by specific antagonists of NO synthase (29), and measures of FMD using this technique correlate with invasive assessments of coronary endothelial function and atherosclerosis (30).”
Method
Low-volume high-intensity interval training rapidly improves cardiopulmonary function in postmenopausal women
Klonizakis, M., Moss, J., Gilbert, S. E., Broom, D. R., Foster, J., & Tew, G. A. (2014) · Menopause The Journal of The North American Menopause Society · doi:10.1097/gme.0000000000000208 · Cited by 79
“380 Diastolic blood pressure, mm Hg 70 (4) 68 (6) 68 (7) 65 (6) 0.”
Risk prediction in cardiovascular disease: The prognostic significance of endothelial dysfunction
Martin, B., & Anderson, T. J. (2009) · Canadian Journal of Cardiology · doi:10.1016/s0828-282x(09)71049-9 · Cited by 79
“The relationship between coronary and peripheral measures of endothelial function is modest to good (40).”
Background
Comparison of New Measures of Vascular Function to Flow Mediated Dilatation as a Measure of Cardiovascular Risk Factors
Philpott, A. C., Lonn, E., Title, L. M., Verma, S., Buithieu, J., Charbonneau, F., & Anderson, T. J. (2009) · The American Journal of Cardiology · doi:10.1016/j.amjcard.2009.01.376 · Cited by 79
Large brachial artery diameter is associated with angiographic coronary artery disease in women
Holubkov, R., Karas, R. H., Pepine, C. J., Rickens, C. R., Reichek, N., Rogers, W. J., Sharaf, B. L., Sopko, G. S., Merz, C. N. B., Kelsey, S. F., et al. (2002) · American Heart Journal · doi:10.1067/mhj.2002.121735 · Cited by 79
Biopsy coupled to quantitative immunofluorescence: a new method to study the human vascular endothelium
Colombo, P. C., Ashton, A. W., Celaj, S., Talreja, A., Banchs, J. E., Dubois, N. B., Marinaccio, M., Malla, S., Lachmann, J. S., Ware, J. A., et al. (2002) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00680.2001 · Cited by 79
“Indirect measurement of reduced nitric oxide (NO) availability in the coronary or in the peripheral circulation is the most frequently assessed parameter of vascular endothelial dysfunction in patients with hypercholesterolemia, diabetes mellitus, hypertension, coronary artery disease, and chronic heart failure (CHF)…”
Background
Assessment of vascular function: flow-mediated constriction complements the information of flow-mediated dilatation
Gori, T., Grotti, S., Dragoni, S., Lisi, M., Stolfo, G. D., Sonnati, S., Fineschi, M., & Parker, J. D. (2009) · Heart · doi:10.1136/hrt.2009.167213 · Cited by 80
Variability of flow-mediated dilation measurements with repetitive reactive hyperemia
Harris, R. A., Padilla, J., Rink, L. D., & Wallace, J. P. (2006) · Vascular Medicine · doi:10.1191/1358863x06vm641oa · Cited by 79
Aging attenuates the protective effect of ischemic preconditioning against endothelial ischemia-reperfusion injury in humans
van den Munckhof, I., Riksen, N. P., Seeger, J. P. H., Schreuder, T. H. A., Borm, G. F., Eijsvogels, T. M. H., Hopman, M. T. E., Rongen, G. A. P. J. M., & Thijssen, D. H. J. (2013) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00054.2013 · Cited by 79
Vascular endothelial dysfunction resulting from l-arginine deficiency in a patient with lysinuric protein intolerance
Kamada, Y., Nagaretani, H., Tamura, S., Ohama, T., Maruyama, T., Hiraoka, H., Yamashita, S., Yamada, A., Kiso, S., Inui, Y., et al. (2001) · Journal of Clinical Investigation · doi:10.1172/jci11260 · Cited by 79
“This is as severe as that observed for patients with coronary artery disease (28%) (41) and is more severe than that reported for chronic smokers (52%) (14).”
Noninvasive Assessment of Endothelial Function in Clinical Practice
Arrebola-Moreno, A. L., Laclaustra, M., & Kaski, J. C. (2011) · Revista Española de Cardiología (English Edition) · doi:10.1016/j.rec.2011.10.004 · Cited by 78
“Coronary endothelial dysfunction is generally assessed using invasive methods, such as the infusion of acetylcholine (ACh) into the coronary artery, where it has been shown to produce a paradoxical vasoconstriction in those arteries affected by atheroma.(17) ACh promotes the release of NO from vessels with an intact”
Method
Chronic kidney disease induces a systemic microangiopathy, tissue hypoxia and dysfunctional angiogenesis
Prommer, H.-U., Maurer, J., von Websky, K., Freise, C., Sommer, K., Nasser, H., Samapati, R., Reglin, B., Guimarães, P., Pries, A. R., et al. (2018) · Scientific Reports · doi:10.1038/s41598-018-23663-1 · Cited by 85
Stability and reproducibility of brachial artery flow-mediated dilation
Welsch, M. A., Allen, J. D., & Geaghan, J. P. (2002) · Medicine & Science in Sports & Exercise · doi:10.1097/00005768-200206000-00009 · Cited by 80
Skeletal Muscle Function during Exercise—Fine-Tuning of Diverse Subsystems by Nitric Oxide
Suhr, F., Gehlert, S., Grau, M., & Bloch, W. (2013) · International Journal of Molecular Sciences · doi:10.3390/ijms14047109 · Cited by 79
“Impaired endothelial function as described in cardiovascular diseases, such as the coronary heart disease [13], is associated with reduced bioavailability of NO and increased generation of superoxide anions.”
Background
Is endothelial function impaired in erectile dysfunction patients?
Kaya, C., Uslu, Z. A., & Karaman, M. İ. (2005) · International Journal of Impotence Research · doi:10.1038/sj.ijir.3901371 · Cited by 78
Comparison of ultrasound assessment of flow‐mediated dilatation in the radial and brachial artery with upper and forearm cuff positions
Agewall, S., Doughty, R. N., Bagg, W., WHALLEY, G. A., Braatvedt, G. D., & Sharpe, N. (2001) · Clinical Physiology · doi:10.1046/j.1365-2281.2001.00302.x · Cited by 78
Nitric oxide is not obligatory for radial artery flow-mediated dilation following release of 5 or 10 min distal occlusion
Pyke, K. E., GREEN, D. J., Weisbrod, C. J., Best, M., Dembo, L. G., O’Driscoll, G., & Tschakovsky, M. E. (2009) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00571.2009 · Cited by 78
“Also supporting the hypothesis that NO dependence is not a necessary condition of FMD’s health relevance, several studies have demonstrated impaired FMD with vascular disease/risk using proximal cuff occlusion (3, 10, 25, 28), in which FMD is minimally dependent on NO (11).”
Background
A comparison of brachial artery row‐mediated vasodilation using upper and lower arm arterial occlusion in subjects with and without coronary risk factors
Vogel, R. A., Corretti, M. C., & Plotnick, G. D. (2000) · Clinical Cardiology · doi:10.1002/clc.4960230805 · Cited by 78
The androgen receptor gene CAG polymorphism is associated with the severity of coronary artery disease in men
Alevizaki, M. K., Cimponeriu, A., Garofallaki, M., Sarika, H.-L., Alevizaki, C. C., Papamichael, C. M., Philippou, G., Anastasiou, E., Lekakis, J. P., & Mavrikakis, M. (2003) · Clinical Endocrinology · doi:10.1046/j.1365-2265.2003.01917.x · Cited by 77
“The latter is an early index of atherosclerosis and we, as well as others, have previously shown that patients with CAD have an impairment of this index of endothelial function (Anderson et al., 1995; Lekakis et al., 1996).”
Result
Heavy and moderate interval exercise training alters low‐flow‐mediated constriction but does not increase circulating progenitor cells in healthy humans
Rakobowchuk, M., Harris, E., Taylor, A., Baliga, V., Cubbon, R. M., Rossiter, H. B., & Birch, K. M. (2011) · Experimental Physiology · doi:10.1113/expphysiol.2011.062836 · Cited by 77
“Email: m.e.rakobowchuk@leeds.ac.uk The progression of cardiovascular disease is blunted by regular exercise training, especially endurance training, while physical inactivity is a primary modifiable risk factor (Celermajer et al. 1994; Anderson et al. 1995; Suwaidi et al. 2000).”
Background
Heterogeneous vasodilator responses of human limbs: influence of age and habitual endurance training
Newcomer, S. C., Leuenberger, U. A., Hogeman, C. S., & Proctor, D. N. (2005) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.01151.2004 · Cited by 77
“dothelial function in the forearm and coronary circulations (1)”
Background
Elimination of Electrically Induced Iontophoretic Artefacts: Implications for Non-Invasive Assessment of Peripheral Microvascular Function
Ferrell, W. R., Ramsay, J. E., Brooks, N., Lockhart, J. C., Dickson, S., McNeece, G. M., Greer, I. A., & Sattar, N. (2002) · Journal of Vascular Research · doi:10.1159/000064515 · Cited by 76
The Dipeptidyl Peptidase-4 Inhibitor Sitagliptin Improves Vascular Endothelial Function in Type 2 Diabetes
Kubota, Y., Miyamoto, M., Takagi, G., Ikeda, T., Kirinoki‐Ichikawa, S., Tanaka, K., & Mizuno, K. (2012) · Journal of Korean Medical Science · doi:10.3346/jkms.2012.27.11.1364 · Cited by 76
“Endothelial dysfunction is a marker of the very early stage of atherosclerosis, and a close relationship exists between the endothelial function in the human coronary circulation and peripheral circulation (36).”
Background
Exaggerated Exercise Blood Pressure Response and Future Cardiovascular Disease
Tzemos, N., Lim, P. O., Mackenzie, I. S., & MacDonald, T. M. (2015) · Journal of Clinical Hypertension · doi:10.1111/jch.12629 · Cited by 76
“The fact that endothelial dysfunction is a systemic condition may explain why peripheral endothelial function (microvascular and macrovascular) correlates with endothelial function in the coronary arteries.(26)”
Background
Usefulness of attenuated heart rate recovery immediately after exercise to predict endothelial dysfunction in patients with suspected coronary artery disease
Huang, P., Leu, H., Chen, J., Cheng, C.-M., Huang, C., Tuan, T., Ding, P. Y., & Lin, S. (2003) · The American Journal of Cardiology · doi:10.1016/j.amjcard.2003.09.004 · Cited by 76
Role of Endothelial Dysfunction in Coronary Artery Disease
Abrams, J. (1997) · The American Journal of Cardiology · doi:10.1016/s0002-9149(97)00379-2 · Cited by 76
Adverse Impact of Mood on Flow-Mediated Dilation
Cooper, D. C., Milic, M. S., Tafur, J., Mills, P. J., Bardwell, W. A., Ziegler, M. G., & Dimsdale, J. E. (2010) · Psychosomatic Medicine · doi:10.1097/psy.0b013e3181cdbfc0 · Cited by 76
“FMD is highly correlated with invasive quantification of the vasomotor responses by epicardial arteries to acetylcholine, which can be considered the gold standard (9,10).”
Background
The Effect of Short-Term Treatment with Simvastatin on Renal Function in Patients with Peripheral Arterial Disease
Youssef, F., Gupta, P., Seifalian, A. M., Myint, F., Mikhailidis, D. P., & Hamilton, G. (2004) · Angiology · doi:10.1177/000331970405500108 · Cited by 75
What Vascular Ultrasound Testing Has Revealed about Pediatric Atherogenesis, and a Potential Clinical Role for Ultrasound in Pediatric Risk Assessment
Slyper, A. H. (2004) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2003-030644 · Cited by 75
Oral L-arginine does not improve endothelial dysfunction in children with chronic renal failure
Bennett-Richards, K., Kattenhorn, M., Donald, A. E., Oakley, G. R., Varghese, Z., Bruckdorfer, K. R., Deanfield, J. E., & Rees, L. (2002) · Kidney International · doi:10.1046/j.1523-1755.2002.00555.x · Cited by 75
Impairment of endothelium-independent vasodilation in patients with hypercalcemia
Neunteufl, T. (1998) · Cardiovascular Research · doi:10.1016/s0008-6363(98)00177-1 · Cited by 75
Endothelial function fluctuates with diurnal variation in the frequency of ischemic episodes in patients with variant angina
Kawano, H., Motoyama, T., Yasue, H., Hirai, N., Waly, H. M., Kugiyama, K., & Ogawa, H. (2002) · Journal of the American College of Cardiology · doi:10.1016/s0735-1097(02)01956-3 · Cited by 73
Assessment of microvascular endothelial function in human skin
NEWTON, D. J., Khan, F., & Belch, J. J. F. (2001) · Clinical Science · doi:10.1042/cs1010567 · Cited by 74
Daily egg consumption in hyperlipidemic adults-Effects on endothelial function and cardiovascular risk
Njike, V., Faridi, Z., Dutta, S., Gonzalez-Simon, A. L., & Katz, D. L. (2010) · Nutrition Journal · doi:10.1186/1475-2891-9-28 · Cited by 73

Authors: Anderson, T. J., Uehata, A., Gerhard, M. D., Meredith, I. T., Knab, S., Delagrange, D., Lieberman, E. H., Ganz, P., Creager, M. A., Yeung, A. C., & Selwyn, A. P.
Affiliations: Brigham and Women's Hospital (US)
ORCID: Anderson, Todd J.
Meredith, Ian T.
Ganz, Peter
Creager, Mark A.
Yeung, Alan C.
Venue: Journal of the American College of Cardiology
Publisher: Elsevier BV
Published: 1995-11
Volume: 26
Issue: 5
Pages: 1235-1241
ISSN: 0735-1097 (ISSN-L)
DOI: 10.1016/0735-1097(95)00327-4
OpenAlex: W1980445357
Cited by: 2,033
References: 24
Citations by year: 2026: 10 · 2025: 18 · 2024: 26 · 2023: 30 · 2022: 25 · 2021: 50 · 2020: 47 · 2019: 42 · 2018: 41 · 2017: 61 · 2016: 67 · 2015: 72 · 2014: 82 · 2013: 75 · 2012: 66
FWCI: 25.71
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 6467 d)
Locations: Journal of the American College of Cardiology (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health (5k04hl002566-04, 5k08hl002787-05, 5k07hl002663-02)
National Heart, Lung, and Blood Institute (HL02663, 1K04-HL-02566, 1K08 HL-02787)
Topics: Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Health and Disease Prevention
Health Sciences › Medicine › Physiology (medical) › Nitric Oxide and Endothelin Effects
Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Function and Risk Factors
Keywords: endothelial dysfunction, coronary artery disease, brachial artery flow-mediated dilation, coronary vasodilation, acetylcholine, reactive hyperemia, cigarette smoking, nitroglycerin, atherosclerosis risk prediction, coronary artery disease screening, brachial artery diameter, vasoconstriction
MeSH terms: Acetylcholine, Adult, Aged, Brachial Artery, Coronary Artery Disease, Coronary Vessels, Endothelium, Vascular, Female, Nitroglycerin, Cardiac Catheterization, Humans, Male, Middle Aged, Predictive Value of Tests, Vasodilation, Vasodilator Agents

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Close relation of endothelial function in the human coronary and peripheral circulations

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