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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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Antioxidant Vitamin C Improves Endothelial Function in Obstructive Sleep Apnea
Grebe, M., Eisele, H., Weißmann, N., Schaefer, C. A., Tillmanns, H., Seeger, W., & Schulz, R. (2006) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.200508-1223oc · Cited by 195
“It occurs mainly as the result of endothelial release of NO (11) and correlates with coronary endothelial function (12).”
Oxidative stress and endothelial dysfunction in vascular disease
Pennathur, S., & Heinecke, J. W. (2007) · Current Diabetes Reports · doi:10.1007/s11892-007-0041-3 · Cited by 187
“Underlining the systemic nature of endothelial dysfunction, Anderson et al. [ 24 ] demonstrated that flow-mediated vasodilation of the brachial arter y correlates with coronary dilation in response to intra-arterial infusion of acetylcholine.”
BackgroundPüntmann, V. O. (2009) · Postgraduate Medical Journal · doi:10.1136/pgmj.2008.073759 · Cited by 182
“Appreciation of effects on endothelial function, recognised as the earliest stage in atherosclerotic disease, serves as a useful example.”
BackgroundHarris, K. F., & Matthews, K. A. (2004) · Psychosomatic Medicine · doi:10.1097/01.psy.0000116719.95524.e2 · Cited by 182
“High levels of experienced anger reported during an anger recall interview were associated with coronary vasoconstriction in narrowed segments of patients with CAD (43).”
BackgroundInfluentialPrognostic value of endothelial function
Quyyumi, A. A. (2003) · The American Journal of Cardiology · doi:10.1016/s0002-9149(03)00430-2 · Cited by 183
Vascular Dysfunction in Chronic Obstructive Pulmonary Disease
Maclay, J. D., McAllister, D., Mills, N. L., Paterson, F., Ludlam, C. A., Drost, E., Newby, D. E., & MacNee, W. (2009) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.200903-0414oc · Cited by 182
“Assessments of vascular function in the peripheral circulation, using either technique, closely relate to assessments of vasomotor function in the coronary circulation ( 35 , 36) and are predictive of cardiovascular events, even in individuals with no known atherosclerosis (14, 37).”
MethodInfluentialAggoun, Y., Farpour‐Lambert, N. J., Marchand, L. M., Golay, E., Maggio, A. B. R., & Beghetti, M. (2008) · European Heart Journal · doi:10.1093/eurheartj/ehm633 · Cited by 186
Reproducibility of Laser Doppler Imaging of Skin Blood Flow as a Tool to Assess Endothelial Function
Kübli, S., Waeber, B., Ave, A. L. D., & Feihl, F. (2000) · Journal of Cardiovascular Pharmacology · doi:10.1097/00005344-200011000-00014 · Cited by 181
Worboys, S., Kotsopoulos, D., Teede, H. J., McGrath, B. P., & Davis, S. R. (2001) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.86.1.7103 · Cited by 181
“Brachial artery FMD has been correlated with coronary endothelial function (11) and with cardiovascular risk factors (10, 12–14).”
BackgroundAdams, M. R., McCredie, R. J., Jessup, W., Robinson, J. T. C., SULLIVAN, D. R., & Celermajer, D. S. (1997) · Atherosclerosis · doi:10.1016/s0021-9150(96)06044-3 · Cited by 181
Schmidt, F. P., Kolle, K., Kreuder, K., Schnorbus, B., Wild, P. S., Hechtner, M., Binder, H., Gori, T., & Münzel, T. F. (2014) · Clinical Research in Cardiology · doi:10.1007/s00392-014-0751-x · Cited by 180
“Importantly, endothelial dysfunction of forearm vessels has been shown to correlate well with endothelial dysfunction (and with the presence of atherosclerosis) in coronary vessels [14] and it has been shown to be associated with future cardiovascular events in patients with coronary and peripheral artery disease, hea…”
BackgroundPeripheral Endothelial Function and Cardiovascular Events in High‐Risk Patients
Matsuzawa, Y., Sugiyama, S., Sumida, H., Sugamura, K., Nozaki, T., Ohba, K., Matsubara, J., Kurokawa, H., Fujisue, K., Konishi, M., et al. (2013) · Journal of the American Heart Association · doi:10.1161/jaha.113.000426 · Cited by 180
Arterial stiffness or endothelial dysfunction as a surrogate marker of vascular risk
Anderson, T. J. (2006) · Canadian Journal of Cardiology · doi:10.1016/s0828-282x(06)70990-4 · Cited by 178
“In addition, coronary atherosclerosis is characterized by peripheral vessel endothelial dysfunction (61).”
BackgroundSelf-citationPlatelet-Derived Nitric Oxide Signaling and Regulation
Gkaliagkousi, Ε., Ritter, J. M., & Ferro, A. (2007) · Circulation Research · doi:10.1161/circresaha.107.158410 · Cited by 175
Noninvasive Vascular Function Measurement in the Community
Schnabel, R. B., Schulz, A., Wild, P. S., Sinning, C., Wilde, S., Eleftheriadis, M. S., Herkenhoff, S., Zeller, T., Lubos, E., Lackner, K. J., et al. (2011) · Circulation Cardiovascular Imaging · doi:10.1161/circimaging.110.961557 · Cited by 176
Turner, J., Belch, J. J. F., & Khan, F. (2008) · Trends in Cardiovascular Medicine · doi:10.1016/j.tcm.2008.02.001 · Cited by 175
“As with all techniques that assess endothelial function in the peripheral vessels, the assumption is made that 109 measurements made here are representative of generalized endothelial function (Anderson et al. 1995).”
BackgroundMethodThe eye, the kidney, and cardiovascular disease: old concepts, better tools, and new horizons
Farrah, T. E., Dhillon, B., Keane, P. A., Webb, D. J., & Dhaun, N. (2020) · Kidney International · doi:10.1016/j.kint.2020.01.039 · Cited by 184
Effects of Antihypertensive Drugs on Endothelial Dysfunction
Taddei, S., Virdis, A., Ghiadoni, L., Sudano, I., & Salvetti, A. (2002) · Drugs · doi:10.2165/00003495-200262020-00003 · Cited by 174
“36) between endothelium-dependent vasodilation tested in different vascular beds in the same individuals.[69] It may not be warranted to start with results obtained in peripheral circulation and extrapolate conclusions on the presumption that they will be applicable to more important vascular districts such as the cor…”
BackgroundMotoyama, T., Kawano, H., Kugiyama, K., Hirashima, O., Ohgushi, M., Tsunoda, R., Moriyama, Y., Miyao, Y., Yoshimura, M., Ogawa, H., et al. (1998) · Journal of the American College of Cardiology · doi:10.1016/s0735-1097(98)00447-1 · Cited by 170
“A previous report showed a close relation in the magnitude of endothelium-dependent vasodilation between coronary arteries and brachial arteries (19), and in the present study, all the patients with CSA had coronary spasm induced by intracoronary injection of acetylcholine, an endothelium-dependent Figure 6.”
ResultNoninvasive Assessment of Endothelium-Dependent Flow-Mediated Dilation of the Brachial Artery
Uehata, A., Lieberman, E. H., Gerhard, M. D., Anderson, T. J., Ganz, P., Polak, J. F., Creager, M. A., & Yeung, A. C. (1997) · Vascular Medicine · doi:10.1177/1358863x9700200203 · Cited by 171
Aortic valve sclerosis is associatedwith systemic endothelial dysfunction
Poggianti, E., Venneri, L., Chubuchny, V., Jambrik, Z., Baroncini, L. A. V., & Picano, E. (2002) · Journal of the American College of Cardiology · doi:10.1016/s0735-1097(02)02622-0 · Cited by 170
Assessment of endothelial function using peripheral waveform analysis
Hayward, C., Kraidly, M., Webb, C. M., & Collins, P. D. (2002) · Journal of the American College of Cardiology · doi:10.1016/s0735-1097(02)01991-5 · Cited by 169
“nique is the close relationship demonstrated between peripheral endothelial dysfunction and coronary atheroma (6,7).”
BackgroundOral folate enhances endothelial function in hyperhomocysteinaemic subjects
Bellamy, McDowell, W., Ramsey, Brownlee, Newcombe, & Lewis (1999) · European Journal of Clinical Investigation · doi:10.1046/j.1365-2362.1999.00527.x · Cited by 168
Evaluating endothelial function in humans: a guide to invasive and non-invasive techniques
Tousoulis, D., Antoniades, C., & Stefanadis, C. (2005) · Heart · doi:10.1136/hrt.2003.032847 · Cited by 167
The atherogenic lipoprotein phenotype and vascular endothelial dysfunction
Sattar, N. A., Petrie, J. R., & Jaap, A. J. (1998) · Atherosclerosis · doi:10.1016/s0021-9150(98)00037-9 · Cited by 162
Montero, D., Walther, G., Pérez‐Martin, A., Roche, E., & Vinet, A. (2011) · Obesity Reviews · doi:10.1111/j.1467-789x.2011.00956.x · Cited by 166
“Moreover, FMD has been found to be inversely correlated to increased cardiovascular morbidity and mortality and to coronary endothelial function in obese adults (67).”
BackgroundImpaired endothelial function in arterial hypertension and hypercholesterolemia
John, S., & Schmieder, R. E. (2000) · Journal of Hypertension · doi:10.1097/00004872-200018040-00002 · Cited by 167
Brevetti, G., Silvestro, A., Giacomo, S. D., Bucur, R., Donato, A. D., Schiano, V., & Scopacasa, F. (2003) · Journal of Vascular Surgery · doi:10.1016/s0741-5214(03)00124-1 · Cited by 165
“7]* Fibrinogen (mg/dL) 200 [177; 293] 374 [273; 453]* Treatment Antiplatelets 40 (77) 29 (80) ACE inhibitors 22 (42) 14 (39) Calcium antagonists 21 (40) 17 (47) -Blockers 7 (13) 4 (11) Nitrates 17 (33) 13 (36) Statins 19 (37) 15 (42) Oral hypoglycemic agents 13 (25) 9 (25) Insulin 4 (8) 2 (6)”
Androgen Deprivation Is Associated With Enhanced Endothelium-Dependent Dilatation in Adult Men
Herman, S. M., Robinson, J. T. C., McCredie, R. J., Adams, M. R., Boyer, M. J., & Celermajer, D. S. (1997) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/01.atv.17.10.2004 · Cited by 165
Effect of Coffee on Endothelial Function in Healthy Subjects: The Role of Caffeine
PAPAMICHAEL, C. M., AZNAOURIDIS, K. A., KARATZIS, E. N., KARATZI, K. N., STAMATELOPOULOS, K. S., VAMVAKOU, G., LEKAKIS, J. P., & MAVRIKAKIS, M. E. (2005) · Clinical Science · doi:10.1042/cs20040358 · Cited by 161
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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