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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Forearm reactive hyperemia and mortality in end-stage renal disease
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“In a previous study a close relation of vasodilatory function in the human coronary and forearm circulations has been demonstrated, and the latter can be a useful surrogate in assessing the systemic endothelial function [31].”
Background
Effects of GH replacement on endothelial function and large‐artery stiffness in GH‐deficient adults: a randomized, double‐blind, placebo‐controlled study
Smith, J. C., Evans, M., Wilkinson, I. B., Goodfellow, J., Cockcroft, J., Scanlon, M. F., & Davies, J. S. (2002) · Clinical Endocrinology · doi:10.1046/j.1365-2265.2002.01514.x · Cited by 132
“Endothelial dysfunction tends to be a generalized phenomenon with close associations between endothelial function in the human coronary and peripheral circulation (Anderson et al., 1995).”
Background
Effects of Race and Hypertension on Flow-Mediated and Nitroglycerin-Mediated Dilation of the Brachial Artery
Gokce, N., Holbrook, M., Duffy, S. J., Demissie, S., Cupples, L. A., Biegelsen, E. S., Keaney, J. F., Loscalzo, J., & Vita, J. A. (2001) · Hypertension · doi:10.1161/hy1201.096575 · Cited by 132
The acute effect of green tea consumption on endothelial function in healthy individuals
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Effects of plant sterol and stanol ester consumption on lipid metabolism, antioxidant status and markers of oxidative stress, endothelial function and low-grade inflammation in patients on current statin treatment
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“Flow mediated dilation is a well-accepted measurement of endothelial dysfunction (Anderson et al., 1995) and seems mainly related to vascular tone.”
Background
Menstrual Cyclic Variation of Myocardial Ischemia in Premenopausal Women with Variant Angina
Kawano, H., Motoyama, T., Ohgushi, M., Kugiyama, K., Ogawa, H., & Yasue, H. (2001) · Annals of Internal Medicine · doi:10.7326/0003-4819-135-11-200112040-00009 · Cited by 131
“Because endothelial function of the brachial artery and of the coronary artery are closely related (13, 14), this modulation of endothelium-dependent dilation in the brachial artery probably occurs in the coronary arteries as well.”
Background
Endothelial Dysfunction in Childhood Infection
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Antenatal glucocorticoid exposure and long-term alterations in aortic function and glucose metabolism
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The CAG Repeat Polymorphism in the AR Gene Affects High Density Lipoprotein Cholesterol and Arterial Vasoreactivity
Zitzmann, M., Brune, M., Kornmann, B., Gromoll, J., von Eckardstein, S., von Eckardstein, A., & Nieschlag, E. (2001) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.86.10.7889 · Cited by 130
“are important risk factors for atherosclerosis (38, 47, 57).”
Atorvastatin but not l-arginine improves endothelial function in type I diabetes mellitus: a double-blind study
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Point: Flow-mediated dilation does reflect nitric oxide-mediated endothelial function
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American Society of Echocardiography Report
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Diffuse endothelial dysfunction is common to ANCA associated systemic vasculitis and polyarteritis nodosa
Filer, A. D., Gardner-Medwin, J. M., Thambyrajah, J., Raza, K., Carruthers, D. M., Stevens, R. J., Liu, L., Lowe, S. E., Townend, J., & Bacon, P. A. (2003) · Annals of the Rheumatic Diseases · doi:10.1136/ard.62.2.162 · Cited by 129
Noninvasive Assessment of Endothelial Function in the Skin Microcirculation
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Cardiovascular effects of flavanol-rich chocolate in patients with heart failure
Flammer, A. J., Sudano, I., Wolfrum, M., Thomas, R., Enseleit, F., Periat, D., Kaiser, P., Hirt, A., Hermann, M., Serafini, M., et al. (2011) · European Heart Journal · doi:10.1093/eurheartj/ehr448 · Cited by 127
“It correlates with coronary endothelial function and is predictive of future coronary events.(6) –8”
Background
Pioglitazone increases the numbers and improves the functional capacity of endothelial progenitor cells in patients with diabetes mellitus
Wang, C., Ting, M., Verma, S., Kuo, L., Yang, N., Hsieh, C., Wang, S.-Y., Hung, A., & Cherng, W. (2006) · American Heart Journal · doi:10.1016/j.ahj.2006.07.029 · Cited by 127
Nitric oxide signalling in the regulation of cardiovascular and platelet function
Gkaliagkousi, Ε. (2010) · Frontiers in bioscience · doi:10.2741/3828 · Cited by 124
Pediatric Precursors of Adult Cardiovascular Disease: Noninvasive Assessment of Early Vascular Changes in Children and Adolescents
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Atherosclerosis: from lesion formation to plaque activation and endothelial dysfunction
Keaney, J. F. (2000) · Molecular Aspects of Medicine · doi:10.1016/s0098-2997(00)00005-4 · Cited by 124
Evidence of Endothelial Dysfunction in Patients With Inflammatory Bowel Disease
Roifman, I., Sun, Y., Fedwick, J. P., Panaccione, R., Buret, A. G., Liu, H., Rostom, A., Anderson, T. J., & Beck, P. L. (2008) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2008.10.021 · Cited by 123
Acute Reversal of Endothelial Dysfunction in the Elderly After Antioxidant Consumption
Wray, D. W., Nishiyama, S. K., Harris, R. A., Zhao, J., McDaniel, J., Fjeldstad, A. S., Witman, M. A., Ives, S. J., Barrett‐O’Keefe, Z., & Richardson, R. S. (2012) · Hypertension · doi:10.1161/hypertensionaha.111.189456 · Cited by 126
“correlates well with coronary artery reactivity.(17) Importantly, both coronary(18) and peripheral(19,20) vasodilator function have been convincingly documented to predict future cardiovascular events, and, as such, assessment of endotheliumdependent vasodilation may provide valuable prognostic and diagnostic patient…”
Dose-dependent effects of omega-3-polyunsaturated fatty acids on systolic left ventricular function, endothelial function, and markers of inflammation in chronic heart failure of nonischemic origin
Moertl, D., Hammer, A., Steiner, S., Hutuleac, R., Vonbank, K., & Berger, R. (2011) · American Heart Journal · doi:10.1016/j.ahj.2011.02.011 · Cited by 124
Evidence of microvascular dysfunction in heart failure with preserved ejection fraction
Lee, J. F., Barrett‐O’Keefe, Z., Garten, R. S., Nelson, A. D., Ryan, J. J., Nativi, J. N., Richardson, R. S., & Wray, D. W. (2015) · Heart · doi:10.1136/heartjnl-2015-308403 · Cited by 124
Morning attenuation of endothelium‐dependent, flow‐mediated dilation in healthy young men: Possible connection to morning peak of cardiac events?
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Effect of exercise training on endothelial function in heart failure patients: A systematic review meta-analysis
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Enhanced peripheral vasodilation in humans after a fatty meal
Raitakari, O. T., Lai, N. C. H., Griffiths, K. A., McCredie, R. J., SULLIVAN, D. R., & Celermajer, D. S. (2000) · Journal of the American College of Cardiology · doi:10.1016/s0735-1097(00)00758-0 · Cited by 123
“Endothelial function tested by the described method in the brachial artery is due predominantly to nitric oxide release by the endothelium (12) and correlates well with coronary endothelial function (13).”
Method
Non-invasive assessment of microvascular endothelial function by laser doppler flowmetry in patients with essential hypertension
Farkas, K., Kolossváry, E., Járai, Z., Nemcsik, J., & Farsang, C. (2004) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2003.11.015 · Cited by 123
Elevated Blood Pressure in Adolescent Boys Predicts Endothelial Dysfunction
Juonala, M., Viikari, J. S. A., Rönnemaa, T., Helenius, H. Y. M., Taittonen, L. M., & Raitakari, O. T. (2006) · Hypertension · doi:10.1161/01.hyp.0000237666.78217.47 · Cited by 123
Estrogen Replacement Reverses Endothelial Dysfunction in Postmenopausal Women
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Human endothelial dysfunction: EDRFs
Flammer, A. J., & Lüscher, T. F. (2010) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/s00424-010-0822-4 · Cited by 127
“Thereby, the change in diameter of the studied blood vessel is assessed by ultrasound at baseline and during reactive hyperemia (Fig. 2). This response is mainly NO-mediated as demonstrated by Joannides et al. [50, 51] (Fig. 3). Moreover, at least in patient populations, peripheral endothelial function as assessed by…”
Noninvasive Visualization of Coronary Artery Endothelial Function in Healthy Subjects and in Patients With Coronary Artery Disease
Hays, A. G., Hirsch, G. A., Kelle, S., Gerstenblith, G., Weiss, R. G., & Stuber, M. (2010) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2010.06.036 · Cited by 120
Dietary flavonoids: effects on endothelial function and blood pressure
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Global impairment of brachial, carotid, and aortic vascular function in young smokers
Wiesmann, F., Petersen, S. E., Leeson, P., Francis, J. M., Robson, M. D., Wang, Q., Choudhury, R. P., Channon, K. M., & Neubauer, S. (2004) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2004.08.033 · Cited by 120
Endothelial Function as a Functional Expression of Cardiovascular Risk Factors
Reriani, M., Lerman, L. O., & Lerman, A. (2010) · Biomarkers in Medicine · doi:10.2217/bmm.10.61 · Cited by 120
Long-Term Prognostic Role of Flow-Mediated Dilatation of the Brachial Artery After Acute Coronary Syndromes Without ST Elevation
Karatzis, E. N., Ikonomidis, I., Vamvakou, G. D., Papaioannou, T. G., Protogerou, A. D., Andreadou, I., Voidonikola, P. T., Karatzi, K., Papamichael, C. M., & Lekakis, J. P. (2006) · The American Journal of Cardiology · doi:10.1016/j.amjcard.2006.06.043 · Cited by 119
Systemic Regulation of Vascular NAD(P)H Oxidase Activity and Nox Isoform Expression in Human Arteries and Veins
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Reference intervals for brachial artery flow-mediated dilation and the relation with cardiovascular risk factors
Holder, S. M., Bruno, R. M., Shkredova, D. A., Dawson, E. A., Jones, H., Hopkins, N. D., Hopman, M. T. E., Bailey, T. G., Coombes, J. S., Askew, C. D., et al. (2021) · Hypertension · doi:10.1161/hypertensionaha.120.15754 · Cited by 118
Clinical safety of blood flow-restricted training? A comprehensive review of altered muscle metaboreflex in cardiovascular disease during ischemic exercise
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Endothelial dysfunction occurs in children with two genetic hyperlipidemias: Improvement with antioxidant vitamin therapy
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Endothelial dysfunction in conduit arteries and in microcirculation. Novel therapeutic approaches
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“Brachial artery FMD has been established as the most commonly used technique (Anderson et al., 1995; D. Sun et al., 1999).”
Method
Flow mediated dilation of the brachial artery: an investigation of methods requiring further standardization
Peretz, A., Leotta, D. F., Sullivan, J. H., Trenga, C. A., Sands, F. N., Aulet, M., Paun, M. K., Gill, E. A., & Kaufman, J. D. (2007) · BMC Cardiovascular Disorders · doi:10.1186/1471-2261-7-11 · Cited by 120
“While assessment of FMD of the brachial artery either with proximal (upper arm), or distal (forearm) occlusion has been found to be correlated with coronary endothelial function[12,13], we evaluated whether other test characteristics may provide a basis for selecting one approach over the other.”

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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