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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Background
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Electrical stimulation-evoked resistance exercise therapy improves arterial health after chronic spinal cord injury
Stoner, L. R., Sabatier, M. J., Mahoney, E. T., Dudley, G. A., & McCully, K. K. (2006) · Spinal Cord · doi:10.1038/sj.sc.3101940 · Cited by 52
Adiponectin is a better predictor of endothelial function of the coronary artery than HOMA-R, body mass index, immunoreactive insulin, or triglycerides
Okui, H., Hamasaki, S., Ishida, S., Kataoka, T., Orihara, K., Fukudome, T., Ogawa, M., Oketani, N., Saihara, K., Shinsato, T., et al. (2007) · International Journal of Cardiology · doi:10.1016/j.ijcard.2007.03.116 · Cited by 52
Brachial artery low-flow-mediated constriction is increased early after coronary intervention and reduces during recovery after acute coronary syndrome: characterization of a recently described index of vascular function
Spiro, J. R., Digby, J. E., Ghimire, G., Mason, M. J., Mitchell, A. G., Ilsley, C. D. J., Donald, A. E., Dalby, M. C. D., & Kharbanda, R. K. (2010) · European Heart Journal · doi:10.1093/eurheartj/ehq401 · Cited by 52
Protective effects of dark chocolate on endothelial function and diabetes
Grassi, D., Desideri, G., & Ferri, C. (2013) · Current Opinion in Clinical Nutrition & Metabolic Care · doi:10.1097/mco.0b013e3283659a51 · Cited by 52
Cardiac syndrome X: Current concepts
Singh, M., Singh, S., Arora, R. R., & Khosla, S. (2010) · International Journal of Cardiology · doi:10.1016/j.ijcard.2009.11.021 · Cited by 52
Endothelial Dysfunction in Patients with Coronary Artery Disease: A Comparison of Three Frequently Reported Tests
Monnink, S. H. J., van Haelst, P. L., Boven, A. J. V., Stroes, E. S. G., Tio, R. A., Plokker, T. W. M., Smit, A. J., Veeger, N. J. G. M., Crijns, H. J. G. M., & van Gilst, W. H. (2002) · Journal of Investigative Medicine · doi:10.2310/6650.2002.33513 · Cited by 52
“In reference to the correlation coefficient of 0.36 as reported by Anderson ( 7 ), in our study with 17”
BackgroundMethodResultInfluential
The Effect of Statin Therapy on Endothelial Function in Type 2 Diabetes Without Manifest Cardiovascular Disease
Beishuizen, E. D., Tamsma, J. T., Jukema, J. W., van de Ree, M. A., van der Vijver, J. C. M., Meinders, A. E., & Huisman, M. V. (2005) · Diabetes Care · doi:10.2337/diacare.28.7.1668 · Cited by 52
Statin therapy improves brachial artery endothelial function in nephrotic syndrome
Dogra, G. K., Watts, G. F., Herrmann, S., Thomas, M., & Irish, A. B. (2002) · Kidney International · doi:10.1046/j.1523-1755.2002.00483.x · Cited by 52
Low fingertip temperature rebound measured by digital thermal monitoring strongly correlates with the presence and extent of coronary artery disease diagnosed by 64-slice multi-detector computed tomography
Ahmadi, N., Nabavi, V., Nuguri, V., Hajsadeghi, F., Flores, F. R., Akhtar, M. W., Kleis, S. J., Hecht, H. S., Naghavi, M., & Budoff, M. J. (2009) · International journal of cardiac imaging · doi:10.1007/s10554-009-9476-8 · Cited by 52
“Indeed, endothelial cells exist in all vascular beds, explaining the common root of vascular disease in various organs (such as heart, brain, kidney, eyes, legs, and urogenital) and the close correlation reported between peripheral and coronary vascular reactivity [27–29].”
Background
Challenges, concerns and common problems: physiological consequences of spinal cord injury and microgravity
Scott, J. M., Warburton, D. E. R., Williams, D., Whelan, S., & Krassioukov, A. (2011) · Spinal Cord · doi:10.1038/sc.2010.53 · Cited by 50
Endothelial ischemia-reperfusion injury in humans: association with age and habitual exercise
DeVan, A. E., Umpierre, D., Harrison, M., Lin, H.-F., Tarumi, T., Renzi, C., Dhindsa, M., Hunter, S. D., & Tanaka, H. (2011) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00845.2010 · Cited by 50
“Brachial artery FMD was chosen as a surrogate model of the coronary arteries because this measure is strongly associated with gold-standard measures of coronary artery function (2).”
Method
Targeting Inflammation Using Salsalate in Patients With Type 2 Diabetes: Effects on Flow-Mediated Dilation (TINSAL-FMD)
Goldfine, A. B., Buck, J. S., Desouza, C. V., Fonseca, V. A., Chen, Y.-D. I., Shoelson, S. E., Jablonski, K. A., Creager, M. A., & for the TINSAL-FMD (Targeting Inflammation Using Salsalate in Type 2 Diabetes–Flow-Mediated Dilation) Ancillary Study Team (2013) · Diabetes Care · doi:10.2337/dc13-0859 · Cited by 51
“Endothelial function in peripheral conduit arteries reflects function in the human coronary circulation (12), and impaired endothelium-dependent vasodilation predicts cardiovascular events (13,14).”
Background
The impact of baseline artery diameter on flow-mediated vasodilation: a comparison of brachial and radial artery responses to matched levels of shear stress
Jazuli, F., & Pyke, K. E. (2011) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00487.2011 · Cited by 51
Physiological adaptation of endothelial function to pregnancy: systematic review and meta‐analysis
van Balen, V. A. L., van Gansewinkel, T. A. G., de Haas, S., van Kuijk, S. M. J., van Drongelen, J., Ghossein‐Doha, C., & Spaanderman, M. E. A. (2017) · Ultrasound in Obstetrics and Gynecology · doi:10.1002/uog.17431 · Cited by 51
Obesity and insulin resistance but not hyperandrogenism mediates vascular dysfunction in women with polycystic ovary syndrome
Dokras, A., Jagasia, D. H., Maifeld, M., Sinkey, C. A., Voorhis, B. J. V., & Haynes, W. G. (2006) · Fertility and Sterility · doi:10.1016/j.fertnstert.2006.05.038 · Cited by 52
Effect of Nebivolol and Atenolol on Brachial Artery Flow-Mediated Vasodilation in Patients with Coronary Artery Disease
Lekakis, J. P., Protogerou, A. D., Papamichael, C. M., Vamvakou, G. D., Iconomidis, I., Fıcı, F., & Mavrikakis, M. (2005) · Cardiovascular Drugs and Therapy · doi:10.1007/s10557-005-3117-9 · Cited by 51
“Endothelial dysfunction is considered to be the first step in atherogenesis as well as a predictor of adverse cardiovascular events in patients with coronary artery disease (CAD), while endothelial function improvement is associated with improved clinical outcome.”
BackgroundInfluential
Effect of losartan in aging-related endothelial impairment
Rajagopalan, S., Brook, R. D., Mehta, R. H., Supiano, M. A., & Pitt, B. (2002) · The American Journal of Cardiology · doi:10.1016/s0002-9149(01)02297-4 · Cited by 51
Comparison of effects of ascorbic acid on endothelium-dependent vasodilation in patients with chronic congestive heart failure secondary to idiopathic dilated cardiomyopathy versus patients with effort angina pectoris secondary to coronary artery disease
Ito, K., Akita, H., Kanazawa, K., Yamada, S., Terashima, M., Matsuda, Y., & Yokoyama, M. (1998) · The American Journal of Cardiology · doi:10.1016/s0002-9149(98)00449-4 · Cited by 51
Treatment with irbesartan or atenolol improves endothelial function in essential hypertension
Mühlen, B. V. Z., Kahan, T., Hägg, A., Millgård, J., & Lind, L. (2001) · Journal of Hypertension · doi:10.1097/00004872-200110000-00015 · Cited by 51
Testosterone as a Modulator of Vascular Behavior
Littleton‐Kearney, M. T., & Hurn, P. D. (2004) · Biological Research For Nursing · doi:10.1177/1099800403262927 · Cited by 49
The Epidemiology of Vascular Dysfunction Relating to Chronic Obstructive Pulmonary Disease and Emphysema
Barr, R. G. (2011) · Proceedings of the American Thoracic Society · doi:10.1513/pats.201101-008mw · Cited by 50
Prevalence and clinical characteristics of carotid atherosclerosis in newly diagnosed patients with ketosis-onset diabetes: a cross-sectional study
Li, L., Zhao, C.-C., Ren, Y., Tu, Y., Lu, J., Wu, X., Zhang, W., Zhu, J., Li, M., Yu, L., et al. (2013) · Cardiovascular Diabetology · doi:10.1186/1475-2840-12-18 · Cited by 50
Single passive leg movement assessment of vascular function: contribution of nitric oxide
Broxterman, R. M., Trinity, J. D., Gifford, J. R., Kwon, O. S., Kithas, A. C., Hydren, J. R., Nelson, A. D., MORGAN, D. E., Jessop, J. E., Bledsoe, A. D., et al. (2017) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00533.2017 · Cited by 50
“THE BIOAVAILABILITY OF NITRIC OXIDE (NO), a molecule with important cardioprotective effects, is mechanistically linked to the endothelial dysfunction that is commonplace in aging and disease (3, 9, 13, 16, 17, 25, 28, 33, 35, 39, 44, 45, 52).”
Background
Vascular effects of 5-HT-receptor agonists in patients with migraine headaches
DEHOON, J., Willigers, J. M., Troost, J., Struijker-Boudier, H. A. J., & VANBORTEL, L. (2000) · Clinical Pharmacology & Therapeutics · doi:10.1067/mcp.2000.110502 · Cited by 50
“Although brachial artery flow-induced vasodilation has been reported to correlate well with coronary endothelial function”
Background
Is There a Difference in Vascular Reactivity of the Arms and Legs?
Proctor, D. N., & Newcomer, S. C. (2006) · Medicine & Science in Sports & Exercise · doi:10.1249/01.mss.0000230340.79247.52 · Cited by 50
Influence of various radiographic contrast media on the buckling of endothelial cells
Franke, R., Fuhrmann, R., Hiebl, B., & Jung, F. (2008) · Microvascular Research · doi:10.1016/j.mvr.2008.05.002 · Cited by 50
Endothelial cell dysfunction: The syndrome in making
O’Riordan, E., Chen, J., Brodsky, S. V., Smirnova, I. V., Li, H., & Goligorsky, M. S. (2005) · Kidney International · doi:10.1111/j.1523-1755.2005.00256.x · Cited by 50
“Plethysmographic or ultrasonographic measurements of brachial artery responses to ﬂow or acetylcholine have been advocated as promising markers of ECD, but their sensitivity in detecting coronary artery disease was found to be 49% [29].”
Background
Impairment of flow mediated vasodilatation of brachial artery in patients with primary hyperparathyroidism
Baykan, M., Erem, C., Erdoğan, T., Hacıhasanoğlu, A., Gedikli, Ö., Kırış, A., Küçükosmanoğlu, M., Ersöz, H. Ö., & Çelik, Ş. (2006) · International journal of cardiac imaging · doi:10.1007/s10554-006-9166-8 · Cited by 50
“Conduit artery endothelial dysfunction is associated with abnormal vasomotor responses of the coronary circulation [27, 28].”
Background
Protective effect of atorvastatin on acute systemic inflammation-induced endothelial dysfunction in hypercholesterolaemic subjects
Vlachopoulos, C., Aznaouridis, K., Dagre, A. G., Vasiliadou, C., Masoura, C., Stefanadi, E., Skoumas, J., Pitsavos, C. E., & Stefanadis, C. (2007) · European Heart Journal · doi:10.1093/eurheartj/ehm247 · Cited by 50
Effects of antihypertensive drugs on vascular remodeling: do they predict outcome in response to antihypertensive therapy?
Schiffrin, E. L. (2001) · Current Opinion in Nephrology & Hypertension · doi:10.1097/00041552-200109000-00011 · Cited by 50
Why the endothelium? The endothelium as a target to reduce diabetes-associated vascular disease
Triggle, C. R., Ding, H., Marei, I., Anderson, T. J., & Hollenberg, M. D. (2020) · Canadian Journal of Physiology and Pharmacology · doi:10.1139/cjpp-2019-0677 · Cited by 49
Cardiometabolic Consequences of Gestational Dysglycemia
Brewster, S., Zinman, B., Retnakaran, R. R., & Floras, J. S. (2013) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2013.01.080 · Cited by 49
“Dysfunction of the endothelium is recognized as an early precursor of coronary atherosclerosis (37), which when present is systemic (38), can be assessed in peripheral arteries, and is a surrogate for the coronary vasculature (39).”
Background
Local Association Between Endothelial Dysfunction and Intimal Hyperplasia: Relevance in Peripheral Artery Disease
Heinen, Y., Stegemann, E., Sansone, R., Benedens, K., Wagstaff, R., Balzer, J., Rassaf, T., Lauer, T., Kelm, M., & Heiß, C. (2015) · Journal of the American Heart Association · doi:10.1161/jaha.114.001472 · Cited by 49
Pharmacological inhibition ofS-nitrosoglutathione reductase improves endothelial vasodilatory function in rats in vivo
Chen, Q., Sievers, R. E., Varga, M., Kharait, S., Haddad, D. J., Patton, A. K., Delany, C., Mutka, S. C., Blonder, J. P., Dubé, G. P., et al. (2013) · Journal of Applied Physiology · doi:10.1152/japplphysiol.01302.2012 · Cited by 49
“This relaxation by N6338 was significantly attenuated by pretreatment of rings with 10 M 1H-[1,2,4]oxadiazolo [4,3- ]quinoxalin-1one (ODQ), 100 M NG-monomethyl-L-arginine (L-NMMA), or 300 M 2-(4-carboxyphenyl)-4,5-dihydro-4,4,5,5-tetramethyl-1H-imidazolyl-1-oxy-3oxide (carboxy PTIO) for 30 min before N6338 administrat…”
Method
Morphologic rather than functional or mechanical sonographic parameters of the brachial artery are related to angiographically evident coronary atherosclerosis
Frick, M., Schwarzacher, S. P., Alber, H. F., Rinner, A., Ulmer, H., Pachinger, O. M., & Weidinger, F. F. (2002) · Journal of the American College of Cardiology · doi:10.1016/s0735-1097(02)02480-4 · Cited by 49
“Flow-mediated vasodilation (FMD) as a functional parameter of the brachial artery (BA) has shown correlation with risk factors (8,9) and coronary endothelial function (10).”
BackgroundResult
Endothelial dysfunction in patients with peripheral arterial disease and chronic hyperhomocysteinemia: potential role of ADMA
Sydow, K., Hornig, B., Arakawa, N., Bode‐Böger, S. M., Tsikas, D., Münuzel, T., & Böger, R. H. (2004) · Vascular Medicine · doi:10.1191/1358863x04vm538oa · Cited by 49
Effects of alcohol intake on endothelial function in men
Zilkens, R., Rich, L., Burke, V., Beilin, L. J., Watts, G. F., & Puddey, I. B. (2003) · Journal of Hypertension · doi:10.1097/00004872-200301000-00019 · Cited by 49
Effect of Gemfibrozil ± Niacin ± Cholestyramine on Endothelial Function in Patients With Serum Low-Density Lipoprotein Cholesterol Levels <160 mg/dl and High-Density Lipoprotein Cholesterol Levels <40 mg/dl11The views expressed in this article are those of the authors and do not reflect the official policy of the Department of Defense or other Departments of the US Government.
Andrews, T. C., Whitney, E. J., Green, G., Kalenian, R., & Personius, B. E. (1997) · The American Journal of Cardiology · doi:10.1016/s0002-9149(97)00531-6 · Cited by 49
SPECIAL ARTICLE: NON‐INVASIVE MEASUREMENT OF ENDOTHELIAL FUNCTION
Playford, D. A., & Watts, G. F. (1998) · Clinical and Experimental Pharmacology and Physiology · doi:10.1111/j.1440-1681.1998.tb02269.x · Cited by 49
Effect of medroxyprogesterone acetate plus estradiol on endothelium-dependent vasodilation in postmenopausal women
Kawano, H., Motoyama, T., Hirai, N., Yoshimura, T., Kugiyama, K., Ogawa, H., Okamura, H., & Yasue, H. (2001) · The American Journal of Cardiology · doi:10.1016/s0002-9149(00)01329-1 · Cited by 49
Endothelial dysfunction markers as a therapeutic target for Sildenafil treatment and effects on metabolic control in type 2 diabetes
Mandosi, E., Giannetta, E., Filardi, T., Lococo, M., Bertolini, C., Fallarino, M., Gianfrilli, D., Venneri, M. A., Lenti, L., Lenzi, A., et al. (2015) · Expert Opinion on Therapeutic Targets · doi:10.1517/14728222.2015.1066337 · Cited by 49
Impairment of flow-mediated vasodilatation of brachial artery in patients with Cushing’s Syndrome
Baykan, M., Erem, C., Gedikli, Ö., Hacıhasanoğlu, A., Erdoğan, T., Koçak, M., Durmuş, İ., Korkmaz, L., & Çelik, Ş. (2007) · Endocrine · doi:10.1007/s12020-007-0033-8 · Cited by 48
Hypoglycemic pharmacological treatment of type 2 diabetes: Targeting the endothelium
Nathanson, D., & Nyström, T. (2008) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2008.11.016 · Cited by 48
“FMD correlates well to the endothelial function in the coroary circulation (Anderson et al., 1995) and has been widely used n the last decade (Bots et al., 2005).”
Background
The Correlation Between Coronary Stenosis Index and Flow-Mediated Dilation of the Brachial Artery
Kaku, B., Mizuno, S., Ohsato, K., Murakami, T., Moriuchi, L., Arai, Y., Nio, Y., Hirase, H., Nagata, M., Takahashi, Y., et al. (1998) · Japanese Circulation Journal-english Edition · doi:10.1253/jcj.62.425 · Cited by 48
Impaired brachial artery endothelium dependent flow mediated dilation in systemic lupus erythematosus: preliminary observations
Johnson, S. R., Harvey, P., Floras, J. S., Iwanochko, M., Ibañez, D., Gladman, D. D., & Urowitz, M. B. (2004) · Lupus · doi:10.1191/0961203304lu1072oa · Cited by 48
Erectile dysfunction predicts generalised cardiovascular disease: Evidence from a case–control study
Stuckey, B. G. A., Walsh, J. P., Ching, H. L., Stuckey, A. W., Palmer, N. R., Thompson, P. L., & Watts, G. F. (2006) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2006.08.043 · Cited by 48
Estrogens, Progestins, and Heart Disease
Vogel, R. A., & Corretti, M. C. (1998) · Circulation · doi:10.1161/01.cir.97.13.1223 · Cited by 48

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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