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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Single passive leg movement-induced hyperemia: a simple vascular function assessment without a chronotropic response
Venturelli, M., Layec, G., Trinity, J. D., Hart, C. R., Broxterman, R. M., & Richardson, R. S. (2016) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00806.2016 · Cited by 35
“Much of the appeal of FMD can be linked to the indication that this assessment represents nitric oxide (NO)mediated endothelial function and seems to be a surrogate for coronary artery endothelial function (3).”
Background
Roles of endothelial dysfunction in coronary artery disease
Forgione, M. A., Leopold, J. A., & Loscalzo, J. (2000) · Current Opinion in Cardiology · doi:10.1097/00001573-200011000-00007 · Cited by 35
Lipid profiles and endothelial function with low-dose hormone replacement therapy in postmenopausal women at risk for coronary artery disease: a randomized trial
Mercuro, G., Vitale, C., Fini, M., Zoncu, S., Leonardo, F., & Rosano, G. M. C. (2003) · International Journal of Cardiology · doi:10.1016/s0167-5273(02)00505-3 · Cited by 34
Effect of antihypertensive treatment on small artery remodeling in hypertension
Schiffrin, E. L. (2003) · Canadian Journal of Physiology and Pharmacology · doi:10.1139/y02-158 · Cited by 35
“2001), which has been shown to correlate with coronary vasomotion (Anderson et al. 1995).”
Background
It is not yet the time to stop screening diabetic patients for silent myocardial ischaemia
Valensi, P. E., & Cosson, E. (2010) · Diabetes & Metabolism · doi:10.1016/j.diabet.2010.01.001 · Cited by 34
Circulating levels of vascular endothelial markers in obstructive sleep apnoea syndrome. Effects of nasal continuous positive airway pressure
Zamarrón, C., Riveiro, A., & Gudé, F. (2011) · Archives of Medical Science · doi:10.5114/aoms.2011.26615 · Cited by 34
“It is known that endothelial dysfunction identified in the peripheral vasculature strongly predicts coronary disease [13].”
Background
Rationale and design of dal-VESSEL: a study to assess the safety and efficacy of dalcetrapib on endothelial function using brachial artery flow-mediated vasodilatation
Kastelein, J. J. P., Duivenvoorden, R., Deanfield, J. E., de Groot, E., Jukema, J. W., Kaski, J. C., Münzel, T. F., Taddei, S., Lehnert, V., Burgess, T., et al. (2010) · Current Medical Research and Opinion · doi:10.1185/03007995.2010.536207 · Cited by 34
Association of mitral annular calcification with endothelial dysfunction, carotid intima-media thickness and serum fetuin-A: an observational study
Zıyrek, M., Tayyareci, Y., Yurdakul, S., Şahin, Ş. T., Yıldırımtürk, Ö., & Aytekin, S. (2013) · The Anatolian Journal of Cardiology · doi:10.5152/akd.2013.235 · Cited by 34
Impact of volunteer-related and methodology-related factors on the reproducibility of brachial artery flow-mediated vasodilation
van Mil, A. C. C. M., Greyling, A., Zock, P. L., Geleijnse, J. M., Hopman, M. T. E., Mensink, R. P., Reesink, K. D., GREEN, D. J., Ghiadoni, L., & Thijssen, D. H. J. (2016) · Journal of Hypertension · doi:10.1097/hjh.0000000000001012 · Cited by 34
“The measurement of endothelial function using FMD has become popular in clinically orientated studies, likely because of its noninvasive nature, ability to predict cardiovascular events [4,9–11] and correlation to coronary artery endothelial function [2,12].”
Diabetic endothelial microangiopathy and pulmonary dysfunction
Zhang, L., Jiang, F., Xie, Y., Mo, Y., Zhang, X., & Liu, C. (2023) · Frontiers in Endocrinology · doi:10.3389/fendo.2023.1073878 · Cited by 35
Endothelial dysfunction in renal transplant patients is closely related to serum cyclosporine levels
Mercanoğlu, F., Turkmen, A., Kocaman, O., Pınarbaşı, B., Dursun, M., Selçukbırıcık, F., & Sever, M. Ş. (2004) · Transplantation Proceedings · doi:10.1016/j.transproceed.2004.05.073 · Cited by 34
The Association between Flow-Mediated Dilation and Physical Function in Older Men
Welsch, M. A., Dobrosielski, D. A., Arce‐Esquivel, A. A., Wood, R. H., Ravussin, É., ROWLEY, C., & Jazwinski, S. M. (2008) · Medicine & Science in Sports & Exercise · doi:10.1249/mss.0b013e31816c5552 · Cited by 34
“Typically, a diminished flow-mediation dilation response of the brachial artery has been interpreted as indicating poor functionality of the endothelium and possibly an increased risk of vascular disease or cardiac events (3,27).”
Background
Blunted response to systemic nitric oxide synthase inhibition in the cerebral circulation of patients with Type 2 diabetes
Nazir, F., Alem, M. M., SMALL, M. P., Nell, J. M. C. C., Lees, K. R., Walters, M. R., & Cleland, S. J. (2006) · Diabetic Medicine · doi:10.1111/j.1464-5491.2006.01815.x · Cited by 34
Blood Vessel Function and Cognition in Elderly Patients With Atherosclerosis
Moser, D. J., Hoth, K. F., Robinson, R. G., Paulsen, J. S., Sinkey, C. A., Benjamin, M. L., Schultz, S. K., & Haynes, W. G. (2004) · Stroke · doi:10.1161/01.str.0000145050.35039.51 · Cited by 34
Flow-mediated vasodilation predicts the presence and extent of coronary artery disease assessed by stress thallium imaging
Wu, W., Sharma, S. C., Choudhary, G., Coulter, L., Coccio, E. B., & Eaton, C. B. (2005) · Journal of Nuclear Cardiology · doi:10.1016/j.nuclcard.2005.04.017 · Cited by 34
Atherosclerotic burden in coronary and peripheral arteries in patients with first clinical manifestation of coronary artery disease
Černe, A., & Kranjec, I. (2002) · Heart and Vessels · doi:10.1007/s003800200028 · Cited by 34
Mildly elevated homocysteine concentrations impair endothelium dependent vasodilation in hypercholesterolemic patients
Schlaich, M. P., John, S., Jacobi, J., Lackner, K. J., & Schmieder, R. E. (2000) · Atherosclerosis · doi:10.1016/s0021-9150(00)00412-3 · Cited by 34
Endothelial dysfunction in the kidney transplant population: Current evidence and management strategies
Prabhahar, A., Batta, A., Hatwal, J., Kumar, V., Ramachandran, R., & Batta, A. (2025) · World journal of transplantation · doi:10.5500/wjt.v15.i1.97458 · Cited by 33
“Assessment by some of the techniques has been shown to replicate the endothelial functions in the coronary circulation[193-195].”
In vivo human lower extremity saphenous vein bypass grafts manifest flow mediated vasodilation
Owens, C. D., Wake, N., Conte, M. S., Gerhard‐Herman, M. D., & Beckman, J. A. (2009) · Journal of Vascular Surgery · doi:10.1016/j.jvs.2009.06.022 · Cited by 33
“While previous work has demonstrated a relationship between peripheral and coronary artery endothelium-dependent vasodilation,(16) a relationship between peripheral artery and vein graft endothelial function has not been described.”
Result
Primary Cutaneous Microangiopathy in Heart Recipients
Jung, F., Mrowietz, C., Labarrere, C. A., Schüler, S., & Park, J. W. (2001) · Microvascular Research · doi:10.1006/mvre.2001.2325 · Cited by 33
Effect of a 3-year therapy with the 3-hydroxy-3-methylglutaryl coenzyme a reductase-inhibitor fluvastatin on endothelial function and distensibility of large arteries in hypercholesterolemic renal transplant recipient
Kosch, M., Barenbrock, M., Suwelack, B. M., Schaefer, R. M., Rahn, K. H., & Hausberg, M. (2003) · American Journal of Kidney Diseases · doi:10.1016/s0272-6386(03)00207-5 · Cited by 33
Folic Acid Does Not Improve Endothelial Function in Obese Children and Adolescents
Peña, A. S., Wiltshire, E. J., Gent, R. J., Piotto, L., Hirte, C., & Couper, J. (2007) · Diabetes Care · doi:10.2337/dc06-2505 · Cited by 33
Arterial dysfunction in syndrome X: results of arterial reactivity and pulse wave propagation tests
Kidawa, M., Krzeminska-Pakula, M., Peruga, J. Z., & Kasprzak, J. D. (2003) · Heart · doi:10.1136/heart.89.4.422 · Cited by 33
Endothelial Dysfunction in Patients with Noncomplicated and Complicated Hypertension
Goch, A., Banach, M., Mikhailidis, D. P., Rysz, J., & Goch, J. H. (2009) · Clinical and Experimental Hypertension · doi:10.1080/10641960802409846 · Cited by 33
Assessing endothelial function as a risk factor for cardiovascular disease
Hinderliter, A. L., & Caughey, M. C. (2003) · Current Atherosclerosis Reports · doi:10.1007/s11883-003-0042-x · Cited by 33
Effect of Folic Acid and Betaine Supplementation on Flow-Mediated Dilation: A Randomized, Controlled Study in Healthy Volunteers
Olthof, M. R., Bots, M. L., Katan, M., & Verhoef, P. (2006) · PLoS Clinical Trials · doi:10.1371/journal.pctr.0010010 · Cited by 33
“FMD is associated with endothelial function in coronary arteries of patients [17,18].”
Background
Effects of low-dose metformin and rosiglitazone on biochemical, clinical, metabolic and biophysical outcomes in polycystic ovary syndrome
Mohiyiddeen, L., Watson, A., Apostolopoulos, N. V., Berry, R. A., Alexandraki, K., & Jude, E. B. (2013) · Journal of Obstetrics and Gynaecology · doi:10.3109/01443615.2012.745839 · Cited by 32
“Consequently, patients with PCOS represent a large group of young women at high risk for the development of early onset CVD.”
Background
Associations of Macro- and Microvascular Endothelial Dysfunction With Subclinical Ventricular Dysfunction in End-Stage Renal Disease
Dubin, R. F., Guajardo, I., Ayer, A., Mills, C., Donovan, C., Beussink‐Nelson, L., Scherzer, R., Ganz, P., & Shah, S. J. (2016) · Hypertension · doi:10.1161/hypertensionaha.116.07489 · Cited by 32
“Endothelium-dependent, flow-mediated dilation (FMD) of the brachial artery is a gold-standard, noninvasive method of quantifying endothelial NO bioavailability(7) that correlates with coronary endothelial function.(8) FMD, the percent change in diameter of the brachial artery during hyperemic blood flow, represents ma…”
Endothelial Vascular Function as a Surrogate of Vascular Risk and Aging in Women
Collins, P. D., Maas, A. H. E. M., Prasad, M., Schierbeck, L. L., & Lerman, A. (2020) · Mayo Clinic Proceedings · doi:10.1016/j.mayocp.2019.07.001 · Cited by 32
“Even noninvasively assessed impaired endothelial function has been shown to be independently predictive of future cardiovascular events, as the function of the endothelium may be a marker of vascular aging.(15,20,22-25)”
Background
Relationship Between Noninvasively Measured Endothelial Function and Peripheral Arterial Disease
Medina-Maldonado, F. J., Haro, J. D., Aguilar, E. M., González, A. F., García, J. R. M., & García, F. A. (2008) · Angiology · doi:10.1177/0003319708327787 · Cited by 32
“measured at this level represents the degree of effects at other levels, such as coronary effects.(4) This has proven to be a simple and convenient method for the assessment of endothelial function, and over the last few years all the factors that might affect its reliability have been analyzed to improve its results.”
Short‐ and long‐term changes of flow‐mediated vasodilation in patients under statin therapy
Frick, M., Alber, H. F., Huegel, H., Schwarzacher, S. P., Pachinger, O. M., & Weidinger, F. F. (2002) · Clinical Cardiology · doi:10.1002/clc.4960250610 · Cited by 32
Reduced flow-mediated vasodilation of brachial artery in children with primary snoring
Li, A. M., Au, C. T., Chook, P., Lam, H. S., & Wing, Y. K. (2012) · International Journal of Cardiology · doi:10.1016/j.ijcard.2012.05.108 · Cited by 32
“FMD of the brachial artery correlateswell with both coronary endothelial function [18] and extent of coronary artery atherosclerosis [19].”
Background
Effects of chronic and acute consumption of fruit- and vegetable-puree-based drinks on vasodilation, risk factors for CVD and the response as a result of theeNOSG298T polymorphism
George, T. W., Niwat, C., Waroonphan, S., Gordon, M. H., & Lovegrove, J. A. (2009) · Proceedings of The Nutrition Society · doi:10.1017/s0029665109001165 · Cited by 32
“It has recently been determined that endothelial dysfunction also occurs in the peripheral circulation and the extent of dysfunction is proportional to that occurring in the coronary arteries((10)).”
BackgroundInfluential
Effect of soy isoflavone protein and soy lecithin on endothelial function in healthy postmenopausal women
Evans, M. A., Njike, V. Y., Hoxley, M. L., Pearson, M., & Katz, D. L. (2006) · Menopause The Journal of The North American Menopause Society · doi:10.1097/01.gme.0000227404.83686.1b · Cited by 32
Automated preoperative assessment of endothelial dysfunction and risk stratification for perioperative myocardial injury in patients undergoing non-cardiac surgery
McIlroy, D. R., Chan, M. T. V., Wallace, S. K. A., Symons, J. A., Koo, E. G. Y., Chu, L. C. Y., & Myles, P. S. (2013) · British Journal of Anaesthesia · doi:10.1093/bja/aet354 · Cited by 36
Acute effects of diets rich in almonds and walnuts on endothelial function
Bhardwaj, R., Dod, H. S., Sandhu, M. S., Bedi, R., Dod, S., Konat, G. W., Chopra, H. K., Sharma, R. K., Jain, A. C., & Nanda, N. C. (2018) · Indian Heart Journal · doi:10.1016/j.ihj.2018.01.030 · Cited by 32
Diabetes Mellitus-Associated Atherosclerosis
Calkin, A. C., & Allen, T. J. (2006) · American Journal of Cardiovascular Drugs · doi:10.2165/00129784-200606010-00003 · Cited by 31
Placebo-controlled trial of transdermal estrogen therapy alone in postmenopausal women: effects on arterial compliance and endothelial function
Teede, H. J., Liang, Y.-L., Kotsopoulos, D., Zoungas, S., Craven, R., & McGrath, B. P. (2002) · Climacteric · doi:10.1080/cmt.5.2.160.169 · Cited by 32
Interleukin-6 and interleukin-10 gene polymorphism, endothelial dysfunction, and postoperative prognosis in patients with peripheral arterial disease
Stoica, A. L., Stoica, E., Constantinescu, I., Uscătescu, V., & Ginghină, C. (2010) · Journal of Vascular Surgery · doi:10.1016/j.jvs.2010.01.088 · Cited by 31
HMG‐CoA reductase inhibitors (statins), inflammation, and endothelial progenitor cells—New mechanistic insights of atherosclerosis
Blum, A. (2014) · BioFactors · doi:10.1002/biof.1157 · Cited by 31
“Brachial artery endothelial dysfunction correlates with coronary endothelial function [45], with cardiovascular risk factors [46, 47], and predicts coronary events [48].”
Metabolic Responses in Endothelial Cells Following Exposure to Ketone Bodies
Meroni, E., Papini, N., Criscuoli, F., Casiraghi, M. C., Massaccesi, L., Basilico, N., & Erba, D. (2018) · Nutrients · doi:10.3390/nu10020250 · Cited by 31
“Endothelial dysfunction is another key risk factor for CVD, often resulting from cellular oxidative unbalance [18,19].”
Background
Total nitrogen oxide following exercise testing reflects endothelial function and discriminates health status
Allen, J. D., Cobb, F. R., Kraus, W. E., & Gow, A. J. (2006) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2006.05.016 · Cited by 31
Serum paraoxonase 1 activity, asymmetric dimethylarginine levels, and brachial artery flow-mediated dilatation in women with polycystic ovary syndrome
Soyman, Z., Noyan, V., Tulmaç, M., Yücel, A., Sağsöz, N., Bayrak, T., Bayrak, A., & Çakır, E. (2010) · Fertility and Sterility · doi:10.1016/j.fertnstert.2010.12.011 · Cited by 32
Telmisartan improves absolute walking distance and endothelial function in patients with peripheral artery disease
Zankl, A. R., Ivandic, B., Andrassy, M., Volz, H. C., Krumsdorf, U., Blessing, E., Katus, H. A., & Tiefenbacher, C. (2010) · Clinical Research in Cardiology · doi:10.1007/s00392-010-0184-0 · Cited by 31
“FMD is a widely used, non-invasive tool for the determination of endothelial function [11, 20], and may serve as a surrogate marker for clinical endpoints [32].”
Method
Kidney transplantation improves arterial function measured by pulse wave analysis and endothelium-independent dilatation in uraemic patients despite deterioration of glucose metabolism
Hornum, M., Clausen, P., Idorn, T., Hansen, J. M., Mathiesen, E. R., & Feldt‐Rasmussen, B. (2010) · Nephrology Dialysis Transplantation · doi:10.1093/ndt/gfq704 · Cited by 31
“FMD is a result of endothelial release of nitric oxide (NO) induced by shear stress and administration of the exogenous NO donor NTG results in NID through its direct effect on the vascular smooth muscle cells, and this dilatation is independent of the endothelium [19].”
Background
Arterial function and structure after a 1-year lifestyle intervention in children with nonalcoholic fatty liver disease
Pacifico, L., Arca, M., Anania, C., Cantisani, V., Martino, M. D., & Chiesa, C. (2012) · Nutrition Metabolism and Cardiovascular Diseases · doi:10.1016/j.numecd.2012.08.003 · Cited by 31
“These early atherosclerotic changes, which include impairment of brachial flow-mediated dilation (FMD), and increased carotid intima-media thickness (cIMT) have been found to predict cardiovascular events [4,5].”
Background

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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