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Close relation of endothelial function in the human coronary and peripheral circulations
Open accessAbstract
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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“endothelial dysfunction, which can be defined as a reduced vasodilator response to acetylcholine, is an early prognostic indicator for the onset of cardiovascular disease (168–171).”
From A Critical Review of the Evidence That Metformin Is a Putative Anti-Aging Drug That Enhances Healthspan and Extends Lifespan (2021) · cites this paper as [169]
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BackgroundEndogenous Estrogen and Acetylcholine-Induced Vasodilation in Normotensive Women
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BackgroundDepressed Mood and Flow-Mediated Dilation
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“We, therefore, determined both the endothelium-dependent, flow-mediated vasodilatation in the brachial artery [22,23], which closely correlates with endothelial function of the coronary arteries [24], and plasma levels of endotheliumderived proteins, high levels of which are associated with endothelial injury [25,26]…”
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“Brachial artery FMD correlates well with measures of coronary artery endothelial function and has been shown to be an independent predictor of cardiovascular risk and future adverse cardiovascular events [35, 39, 40].”
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“Endothelial barrier integrity and ECM maturation is achieved by LOX, a key enzyme that is strongly expressed in the endothelium of coronary arteries of humans and animal models [43, 44].”
BackgroundTea, flavonoids, and cardiovascular health: endothelial protection
Grassi, D., Desideri, G., Giosia, P. D., Feo, M. D., Fellini, E., Cheli, P., Ferri, L., & Ferri, C. (2013) · American Journal of Clinical Nutrition · doi:10.3945/ajcn.113.058313 · Cited by 101
“In particular, Anderson et al (39) reported that endothelial dysfunction in the brachial artery presented a high predictive value for abnormal endothelial function in the coronary circulation, as assessed by intracoronary acetylcholine infusion.”
BackgroundA review of endothelial dysfunction in diabetes: a focus on the contribution of a dysfunctional eNOS
Triggle, C. R., & Ding, H. (2010) · Journal of the American Society of Hypertension · doi:10.1016/j.jash.2010.02.004 · Cited by 103
Poitras, V. J., & Pyke, K. E. (2013) · International Journal of Psychophysiology · doi:10.1016/j.ijpsycho.2013.03.019 · Cited by 106
Association Between the Female Athlete Triad and Endothelial Dysfunction in Dancers
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“Abnormal brachial dilation has been shown to have a positive predictive value (95%) for coronary endothelial dysfunction.(6) In addition, Schachinger et al(7) have shown that coronary endothelial vasodilator dysfunction predicts long-term atherosclerotic disease progression and cardiovascular event rates.”
BackgroundLekakis, J. P., Papamichael, C. M., Vemmos, C., Voutsas, A., Stamatelopoulos, S., & Moulopoulos, S. D. (1998) · Journal of the American College of Cardiology · doi:10.1016/s0735-1097(97)00542-1 · Cited by 100
“The brachial vasodilator response to reactive hyperemia was closely related to the coronary vasodilator response to acetylcholine (4) and to the extent of coronary atherosclerosis (17) in patients with atherosclerotic heart disease.”
Kawano, H., Motoyama, T., Kugiyama, K., Hirashima, O., Ohgushi, M., Fujii, H., Ogawa, H., & Yasue, H. (1997) · Journal of the American College of Cardiology · doi:10.1016/s0735-1097(97)00234-9 · Cited by 100
Evaluation of endothelium‐dependent vasodilation in the human peripheral circulation
Lind, L., Hall, J., Larsson, A., Annuk, M., Fellström, B., & Lithell, H. (2000) · Clinical Physiology · doi:10.1046/j.1365-2281.2000.00281.x · Cited by 99
Effect of Treatment on Flow-Dependent Vasodilation of the Brachial Artery in Essential Hypertension
Muiesan, M. L., Salvetti, M., Monteduro, C., Rizzoni, D., Zulli, R., Corbellini, C., Brun, C., & Agabiti‐Rosei, E. (1999) · Hypertension · doi:10.1161/01.hyp.33.1.575 · Cited by 99
Insulin Resistance and Vascular Dysfunction in Nondiabetic Asian Indians
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Ding, H., & Triggle, C. R. (2010) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/s00424-010-0807-3 · Cited by 101
“endothelium-dependent vasodilatation (EDV) is associated with an increased risk of cardiovascular complications during long-term follow-up [6, 7, 60, 71].”
BackgroundMethodPick your Poiseuille: normalizing the shear stimulus in studies of flow-mediated dilation
Parker, B. A., Trehearn, T. L., & Meendering, J. R. (2009) · Journal of Applied Physiology · doi:10.1152/japplphysiol.91302.2009 · Cited by 98
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BackgroundMethodStein, J. H., Merwood, M. A., Bellehumeur, J. L., Aeschlimann, S. E., Korcarz, C. E., Underbakke, G. L., Mays, M. E., & Sosman, J. M. (2004) · American Heart Journal · doi:10.1016/j.ahj.2003.10.018 · Cited by 98
Trigona, B., Aggoun, Y., Maggio, A. B. R., Martin, X., Marchand, L. M., Beghetti, M., & Farpour‐Lambert, N. J. (2010) · The Journal of Pediatrics · doi:10.1016/j.jpeds.2010.04.023 · Cited by 98
Endothelial dysfunction in cardiovascular disease and Flammer syndrome—similarities and differences
Barthelmes, J., Nägele, M. P., Ludovici, V., Ruschitzka, F. T., Sudano, I., & Flammer, A. J. (2017) · The EPMA Journal · doi:10.1007/s13167-017-0099-1 · Cited by 98
“FMD is probably the most popular method to measure endothelial dysfunction due to its non-invasiveness and correlation with coronary vasoreactivity [40], as well as being mainly NO-dependent [39] (though not exclusively [41]).”
MethodZheng, X.-Y., & Liu, L. (2007) · Journal of Lipid Research · doi:10.1194/jlr.r700001-jlr200 · Cited by 83
“Several animal experiments ex vivo have been done to explore the effects of remnants on EDR and the involved mechanisms.”
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Association Between Chronic Caregiving Stress and Impaired Endothelial Function in the Elderly
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Three decades of endothelium research
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Human endothelial dysfunction: EDCFs
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“Despite the scanty relationship between responses from different vascular districts of the same subject [2, 29], the presence of endothelial dysfunction almost invariably results to be an independent predictor of future clinical events wherever detected [25].”
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“Subjects underwent assessment of endothelium-dependent FMD of the right brachial artery, as previously described 22 , at baseline, after 6 weeks of intensive weight loss when dietary adherence would be at its best and glucose and LDL-C were predicted to be at their lowest level, and at 52 weeks.”
Skin microvascular endothelial function as a biomarker in cardiovascular diseases?
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van Baal, W. M., Kenemans, P., EMEIS, J. J., Schalkwijk, C. G., Mijatovic, V., van der Mooren, M. J., Vischer, U. M., & Stehouwer, C. D. A. (1999) · Fertility and Sterility · doi:10.1016/s0015-0282(98)00513-5 · Cited by 96
Arterial Reactivity Is Enhanced in Genetic Males Taking High Dose Estrogens
McCrohon, J. A., Walters, W. A. W., Robinson, J. T. C., McCredie, R. J., Turner, L., Adams, M. R., Handelsman, D. J., & Celermajer, D. S. (1997) · Journal of the American College of Cardiology · doi:10.1016/s0735-1097(97)00063-6 · Cited by 96
“Endothelium-dependent dilation measured in this way is predominantly due to nitric oxide release by the endothelium (15), and this response in the brachial artery correlates well with coronary endothelial function (16).”
BackgroundCarotid intima-media thickness as a surrogate marker of cardiovascular disease in diabetes
Sibal, L., Sibal, L., Agarwal, & Home, P. (2011) · Diabetes Metabolic Syndrome and Obesity · doi:10.2147/dmso.s8540 · Cited by 95
“Endothelial dysfunction in the peripheral vessels are modestly correlated with the endothelial function in the coronary vessels.(18,19) Flow-mediated dilatation in response to postocclusive reactive hyperemia has been used to noninvasively assess endothelial function in the peripheral vascular system.”
The Vascular Endothelium in Hypertension
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Endothelial dysfunction and inflammation: What is the link?
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Hammadah, M., Mheid, I. A., Wilmot, K. A., Ramadan, R., Shah, A. J., Sun, Y. V., Pearce, B. D., Garcia, E. V., Kutner, M., Bremner, J. D., et al. (2016) · Psychosomatic Medicine · doi:10.1097/psy.0000000000000442 · Cited by 94
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Brachial artery endothelial function in residents and fellows working night shifts
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CORP: Ultrasound assessment of vascular function with the passive leg movement technique
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“Indeed, peripheral vascular function assessed by flow-mediated dilation (FMD) has been reported to be partially NO-dependent (19, 84), reflect coronary vascular function (3, 62), and predict the incidence of cardiovascular disease (17, 33, 86, 87).”
BackgroundMethodStrong Relationship Between Vascular Function in the Coronary and Brachial Arteries
Broxterman, R. M., Witman, M. A., Trinity, J. D., Groot, H. J., Rossman, M. J., Park, S., Malenfant, S., Gifford, J. R., Kwon, O. S., Park, S. H., et al. (2019) · Hypertension · doi:10.1161/hypertensionaha.119.12881 · Cited by 93
“A relationship between BA FMD and the acetylcholineinduced coronary artery response was previously documented in 2 studies.(6,7) Although significant, the strength of these relationships was weak (r≈0.”
BackgroundThe endothelium: Dysfunction and beyond
Herrmann, J., & Lerman, A. (2001) · Journal of Nuclear Cardiology · doi:10.1067/mnc.2001.114148 · Cited by 93
Bosello, S. L., Santoliquido, A., Zoli, A., Campli, C. D., Flore, R. A., Tondi, P., & Ferraccioli, G. (2007) · Clinical Rheumatology · doi:10.1007/s10067-007-0803-y · Cited by 93
“There is some evidence that endothelial dysfunction on brachial artery ultrasound imaging may correlate with endothelial dysfunction noted on coronary angiography after acetylcholine injection [23].”
Background
Metadata
- 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)
- 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)
- 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
- 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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