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J Am Coll Cardiol, 1994; 24:1468-1474
© 1994 by the American College of Cardiology Foundation
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Endothelium-dependent dilation in the systemic arteries of asymptomatic subjects relates to coronary risk factors and their interaction

DS Celermajer, KE Sorensen, C Bull, J Robinson, and JE Deanfield

Cardiothoracic Unit, Hospital for Sick Children, London, England, United Kingdom.

OBJECTIVES. This study attempted to assess whether coronary risk factors are associated with endothelial dysfunction in the systemic arteries of asymptomatic men and women. BACKGROUND. Endothelial dysfunction is present in adults with established atherosclerosis. It is not known whether risk factors interact to produce endothelial dysfunction in clinically well subjects early in the natural history. METHODS. Using high resolution ultrasound, we measured arterial diameter at rest, after reactive hyperemia (with increased flow causing endothelium-dependent dilation) and after sublingual nitroglycerin (an endothelium-independent dilator). Arterial responses were studied noninvasively in 500 clinically well, nonhypertensive subjects (252 men, 248 women; mean [+/- SD] age 36 +/- 15 years, range 5 to 73), including 179 current and former smokers. The superficial femoral artery was studied in 46 subjects and the brachial artery in 454. RESULTS. Flow-mediated dilation ranged from -1% to +17%. All arteries dilated in response to administration of nitroglycerin (17 +/- 6%), suggesting an abnormality of endothelial function in subjects with impaired flow-mediated dilation. On univariate analysis, reduced flow-mediated dilation was significantly related to hypercholesterolemia, cigarette smoking, higher blood pressure, male gender, older age, family history of premature vascular disease and larger vessel size (p < 0.01). By multiple stepwise regression analysis, reduced flow-mediated dilation was independently associated with cigarette smoking, older age, male gender and larger vessel size (p < 0.005) but not with total cholesterol level, blood pressure or family history. A composite risk factor score was independently related to flow-mediated dilation (r = -0.30, p < 0.0001), suggesting risk factor interaction. CONCLUSIONS. Loss of endothelium-dependent dilation in the systemic arteries occurs in the preclinical phase of vascular disease and is associated with interaction of the same risk factors known to predispose to atherosclerosis and its complications in later life.


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D. J. Green, J. H. Walsh, A. Maiorana, V. Burke, R. R. Taylor, and J. G. O'Driscoll
Comparison of resistance and conduit vessel nitric oxide-mediated vascular function in vivo: effects of exercise training
J Appl Physiol, August 1, 2004; 97(2): 749 - 755.
[Abstract] [Full Text] [PDF]


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CirculationHome page
N. C. Ward, J. Rivera, J. Hodgson, I. B. Puddey, L. J. Beilin, J. R. Falck, and K. D. Croft
Urinary 20-Hydroxyeicosatetraenoic Acid Is Associated With Endothelial Dysfunction in Humans
Circulation, July 27, 2004; 110(4): 438 - 443.
[Abstract] [Full Text] [PDF]


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CirculationHome page
M. El-Magadmi, H. Bodill, Y. Ahmad, P. N. Durrington, M. Mackness, M. Walker, R. M. Bernstein, and I. N. Bruce
Systemic Lupus Erythematosus: An Independent Risk Factor for Endothelial Dysfunction in Women
Circulation, July 27, 2004; 110(4): 399 - 404.
[Abstract] [Full Text] [PDF]


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J CARDIOVASC PHARMACOL THERHome page
J.-H. Bae, E. Bassenge, K.-Y. Kim, Y.-C. Synn, k.-R. Park, and M. Schwemmer
Effects of Low-Dose Atorvastatin on Vascular Responses in Patients Undergoing Percutaneous Coronary Intervention With Stenting
Journal of Cardiovascular Pharmacology and Therapeutics, July 1, 2004; 9(3): 185 - 192.
[Abstract] [PDF]


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J. Clin. Endocrinol. Metab.Home page
A. H. Slyper
What Vascular Ultrasound Testing Has Revealed about Pediatric Atherogenesis, and a Potential Clinical Role for Ultrasound in Pediatric Risk Assessment
J. Clin. Endocrinol. Metab., July 1, 2004; 89(7): 3089 - 3095.
[Abstract] [Full Text] [PDF]


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Am. J. Physiol. Heart Circ. Physiol.Home page
P. C. E. de Groot, F. Poelkens, M. Kooijman, and M. T. E. Hopman
Preserved flow-mediated dilation in the inactive legs of spinal cord-injured individuals
Am J Physiol Heart Circ Physiol, July 1, 2004; 287(1): H374 - H380.
[Abstract] [Full Text] [PDF]


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CirculationHome page
J. Davignon and P. Ganz
Role of Endothelial Dysfunction in Atherosclerosis
Circulation, June 15, 2004; 109(23_suppl_1): III-27 - III-32.
[Abstract] [Full Text]


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CirculationHome page
M. E. Otto, A. Svatikova, R. B. d. M. Barretto, S. Santos, M. Hoffmann, B. Khandheria, and V. Somers
Early Morning Attenuation of Endothelial Function in Healthy Humans
Circulation, June 1, 2004; 109(21): 2507 - 2510.
[Abstract] [Full Text] [PDF]


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CirculationHome page
U. Landmesser, B. Hornig, and H. Drexler
Endothelial Function: A Critical Determinant in Atherosclerosis?
Circulation, June 1, 2004; 109(21_suppl_1): II-27 - II-33.
[Abstract] [Full Text] [PDF]


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J Am Coll CardiolHome page
H. D. Wu, L. Berglund, C. Dimayuga, J. Jones, R. R. Sciacca, M. R. Di Tullio, and S. Homma
High lipoprotein(a) levels and small apolipoprotein(a) sizes are associated with endothelial dysfunction in a multiethnic cohort
J. Am. Coll. Cardiol., May 19, 2004; 43(10): 1828 - 1833.
[Abstract] [Full Text] [PDF]


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CirculationHome page
J. P. Casas, L. E. Bautista, S. E. Humphries, and A. D. Hingorani
Endothelial Nitric Oxide Synthase Genotype and Ischemic Heart Disease: Meta-Analysis of 26 Studies Involving 23028 Subjects
Circulation, March 23, 2004; 109(11): 1359 - 1365.
[Abstract] [Full Text] [PDF]


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Psychosom. Med.Home page
K. F. Harris and K. A. Matthews
Interactions Between Autonomic Nervous System Activity and Endothelial Function: A Model for the Development of Cardiovascular Disease
Psychosom Med, March 1, 2004; 66(2): 153 - 164.
[Abstract] [Full Text] [PDF]


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J Am Coll CardiolHome page
R. Fathi, B. Haluska, N. Isbel, L. Short, and T. H. Marwick
The relative importance of vascular structure and function in predicting cardiovascular events
J. Am. Coll. Cardiol., February 18, 2004; 43(4): 616 - 623.
[Abstract] [Full Text] [PDF]


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CirculationHome page
E. J. Benjamin, M. G. Larson, M. J. Keyes, G. F. Mitchell, R. S. Vasan, J. F. Keaney Jr, B. T. Lehman, S. Fan, E. Osypiuk, and J. A. Vita
Clinical Correlates and Heritability of Flow-Mediated Dilation in the Community: The Framingham Heart Study
Circulation, February 10, 2004; 109(5): 613 - 619.
[Abstract] [Full Text] [PDF]


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Vasc MedHome page
L. W. Lissin, R. Oka, S. Lakshmi, and J. P Cooke
Isoflavones improve vascular reactivity in post-menopausal women with hypercholesterolemia
Vascular Medicine, February 1, 2004; 9(1): 26 - 30.
[Abstract] [PDF]


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J Am Coll CardiolHome page
D. R. Kaiser, K. Billups, C. Mason, R. Wetterling, J. L. Lundberg, and A. J. Bank
Impaired brachial artery endothelium-dependent and -independent vasodilation in men with erectile dysfunction and no other clinical cardiovascular disease
J. Am. Coll. Cardiol., January 21, 2004; 43(2): 179 - 184.
[Abstract] [Full Text] [PDF]


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J Am Coll CardiolHome page
M. D. Cheitlin
Erectile dysfunction: the earliest sign of generalized vascular disease?
J. Am. Coll. Cardiol., January 21, 2004; 43(2): 185 - 186.
[Full Text] [PDF]


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Am. J. Physiol. Heart Circ. Physiol.Home page
U. Campia, G. Sullivan, M. B. Bryant, M. A. Waclawiw, M. J. Quon, and J. A. Panza
Insulin impairs endothelium-dependent vasodilation independent of insulin sensitivity or lipid profile
Am J Physiol Heart Circ Physiol, January 1, 2004; 286(1): H76 - H82.
[Abstract] [Full Text] [PDF]


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Am. J. Physiol. Heart Circ. Physiol.Home page
D. J. Green, J. H. Walsh, A. Maiorana, M. J. Best, R. R. Taylor, and J. G. O'Driscoll
Exercise-induced improvement in endothelial dysfunction is not mediated by changes in CV risk factors: pooled analysis of diverse patient populations
Am J Physiol Heart Circ Physiol, December 1, 2003; 285(6): H2679 - H2687.
[Abstract] [Full Text] [PDF]


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Vasc MedHome page
A. Silvestro, F. Scopacasa, A. Ruocco, G. Oliva, V. Schiano, C. Zincarelli, and G. Brevetti
Inflammatory status and endothelial function in asymptomatic and symptomatic peripheral arterial disease
Vascular Medicine, November 1, 2003; 8(4): 225 - 232.
[Abstract] [PDF]


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CirculationHome page
P. Ganz and J. A. Vita
Testing Endothelial Vasomotor Function: Nitric Oxide, a Multipotent Molecule
Circulation, October 28, 2003; 108(17): 2049 - 2053.
[Full Text] [PDF]


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CirculationHome page
G. Brevetti, A. Silvestro, V. Schiano, and M. Chiariello
Endothelial Dysfunction and Cardiovascular Risk Prediction in Peripheral Arterial Disease: Additive Value of Flow-Mediated Dilation to Ankle-Brachial Pressure Index
Circulation, October 28, 2003; 108(17): 2093 - 2098.
[Abstract] [Full Text] [PDF]


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Eur Heart JHome page
J. H. Walsh, G. Yong, C. Cheetham, G. F. Watts, G. J. O'Driscoll, R. R. Taylor, and D. J. Green
Effects of exercise training on conduit and resistance vessel function in treated and untreated hypercholesterolaemic subjects
Eur. Heart J., September 2, 2003; 24(18): 1681 - 1689.
[Abstract] [Full Text] [PDF]


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J. Appl. Physiol.Home page
J. H. Walsh, W. Bilsborough, A. Maiorana, M. Best, G. J. O'Driscoll, R. R. Taylor, and D. J. Green
Exercise training improves conduit vessel function in patients with coronary artery disease
J Appl Physiol, July 1, 2003; 95(1): 20 - 25.
[Abstract] [Full Text] [PDF]


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J. Clin. Endocrinol. Metab.Home page
H. Kawano, H. Yasue, A. Kitagawa, N. Hirai, T. Yoshida, H. Soejima, S. Miyamoto, M. Nakano, and H. Ogawa
Dehydroepiandrosterone Supplementation Improves Endothelial Function and Insulin Sensitivity in Men
J. Clin. Endocrinol. Metab., July 1, 2003; 88(7): 3190 - 3195.
[Abstract] [Full Text] [PDF]


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J Am Coll CardiolHome page
G. D. Plotnick, M. C. Corretti, R. A. Vogel, R. Hesslink Jr, and J. A. Wise
Effect of supplemental phytonutrients on impairment of the flow-mediated brachialartery vasoactivity after a single high-fat meal
J. Am. Coll. Cardiol., May 21, 2003; 41(10): 1744 - 1749.
[Abstract] [Full Text] [PDF]


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CirculationHome page
R. S. Barua, J. A. Ambrose, S. Srivastava, M. C. DeVoe, and L.-J. Eales-Reynolds
Reactive Oxygen Species Are Involved in Smoking-Induced Dysfunction of Nitric Oxide Biosynthesis and Upregulation of Endothelial Nitric Oxide Synthase: An In Vitro Demonstration in Human Coronary Artery Endothelial Cells
Circulation, May 13, 2003; 107(18): 2342 - 2347.
[Abstract] [Full Text] [PDF]


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Vasc MedHome page
S. M Bode-Boger, J. Muke, A. Surdacki, G. Brabant, R. H Boger, and J. C Frolich
Oral L-arginine improves endothelial function in healthy individuals older than 70 years
Vascular Medicine, May 1, 2003; 8(2): 77 - 81.
[Abstract] [PDF]


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HypertensionHome page
M. Kimura, Y. Higashi, K. Hara, K. Noma, S. Sasaki, K. Nakagawa, C. Goto, T. Oshima, M. Yoshizumi, and K. Chayama
PDE5 Inhibitor Sildenafil Citrate Augments Endothelium-Dependent Vasodilation in Smokers
Hypertension, May 1, 2003; 41(5): 1106 - 1110.
[Abstract] [Full Text] [PDF]



 
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