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Circulation, Vol 88, 2149-2155, Copyright © 1993 by American Heart Association
DS Celermajer, KE Sorensen, D Georgakopoulos, C Bull, O Thomas, J Robinson and JE Deanfield
BACKGROUND. Cigarette smoking is the most important modifiable risk factor
for atherosclerosis. Endothelial dysfunction is an early event in
atherogenesis, and we hypothesized that smoking might be associated with
endothelial damage in the systemic arteries of otherwise healthy young
adults. METHODS AND RESULTS. We studied noninvasively the brachial arteries
of 200 subjects aged 15 to 57 years, all normotensive, nondiabetic with
cholesterol level < or = 240 mg/dL and no family history of premature
vascular disease: 80 control subjects aged 16 to 56 years (mean, 35), 80
current smokers aged 15 to 55 years (mean, 33), and 40 former smokers aged
25 to 57 years (mean, 38). Total lifetime amount smoked varied from 1 to 75
pack years in the smokers. Using high-resolution ultrasound, vessel
diameter was measured at rest, during reactive hyperemia (with flow
increase causing endothelium- dependent dilation), and after sublingual
glyceryl trinitrate (GTN, an endothelium-independent vasodilator).
Flow-mediated dilation (FMD) was observed in all the control subjects (10
+/- 3.3%; range, 4% to 22%) but was impaired or absent in the smokers (4
+/- 3.9%; range, 0% to 17%; P < .0001). FMD in the smokers was inversely
related to lifetime dose smoked (6.6 +/- 4.0% in very light smokers, 4.0
+/- 3.1% in light smokers, 3.2 +/- 3.2% in moderate smokers, and 2.6 +/-
1.2% in heavy smokers; P < .01). FMD for the former smokers was 5.1 +/-
4.1% (range, 0% to 15%). In a multivariate model adjusting for age, sex,
cholesterol, smoking history, and vessel size, former smoking was
associated with a higher FMD than current smoking (P = .07); when only male
former and current smokers were considered, the higher FMD was significant
(P = .0001) but not for female smokers (P = .24). GTN caused dilation in
all subjects (control subjects, 20 +/- 5.2%; smokers, 17 +/- 5.8%; former
smokers, 17.4 +/- 5.4%). Vessel diameter, baseline flow, and degree of
reactive hyperemia (Doppler estimated) were similar in all groups.
CONCLUSIONS. Cigarette smoking is associated with dose-related and
potentially reversible impairment of endothelium-dependent arterial
dilation in asymptomatic young adults, consistent with endothelial
dysfunction.
ARTICLES
Cigarette smoking is associated with dose-related and potentially reversible impairment of endothelium-dependent dilation in healthy young adults
Cardiothoracic Unit, Hospital for Sick Children, London.
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D. J Green, A. Maiorana, G. O'Driscoll, and R. Taylor Effect of exercise training on endothelium-derived nitric oxide function in humans J. Physiol., November 15, 2004; 561(1): 1 - 25. [Abstract] [Full Text] [PDF]
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K. B. Vallbracht, P. L. Schwimmbeck, U. Kuhl, B. Seeberg, and H.-P. Schultheiss Endothelium-Dependent Flow-Mediated Vasodilation of Systemic Arteries Is Impaired in Patients With Myocardial Virus Persistence Circulation, November 2, 2004; 110(18): 2938 - 2945. [Abstract] [Full Text] [PDF]
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B. Takase, H. Etsuda, Y. Matsushima, M. Ayaori, H. Kusano, A. Hamabe, A. Uehata, F. Ohsuzu, M. Ishihara, and A. Kurita Effect of Chronic Oral Supplementation with Vitamins on the Endothelial Function in Chronic Smokers Angiology, November 1, 2004; 55(6): 653 - 660. [Abstract] [PDF]
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R. H. Boger Asymmetric Dimethylarginine, an Endogenous Inhibitor of Nitric Oxide Synthase, Explains the "L-Arginine Paradox" and Acts as a Novel Cardiovascular Risk Factor J. Nutr., October 1, 2004; 134(10): 2842S - 2847S. [Abstract] [Full Text] [PDF]
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 M S Mahonen, P McElduff, A J Dobson, K A Kuulasmaa, and A E Evans Current smoking and the risk of non-fatal myocardial infarction in the WHO MONICA Project populations Tob. Control, September 1, 2004; 13(3): 244 - 250. [Abstract] [Full Text] [PDF]
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A. Raji, M. D. Gerhard-Herman, M. Warren, S. G. Silverman, V. Raptopoulos, C. S. Mantzoros, and D. C. Simonson Insulin Resistance and Vascular Dysfunction in Nondiabetic Asian Indians J. Clin. Endocrinol. Metab., August 1, 2004; 89(8): 3965 - 3972. [Abstract] [Full Text] [PDF]
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K. E. Pyke, E. M. Dwyer, and M. E. Tschakovsky Impact of controlling shear rate on flow-mediated dilation responses in the brachial artery of humans J Appl Physiol, August 1, 2004; 97(2): 499 - 508. [Abstract] [Full Text] [PDF]
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J. A. Beckman, J. K. Liao, S. Hurley, L. A. Garrett, D. Chui, D. Mitra, and M. A. Creager Atorvastatin Restores Endothelial Function in Normocholesterolemic Smokers Independent of Changes in Low-Density Lipoprotein Circ. Res., July 23, 2004; 95(2): 217 - 223. [Abstract] [Full Text] [PDF]
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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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L. Stoner, M. Sabatier, K. Edge, and K. McCully Relationship between blood velocity and conduit artery diameter and the effects of smoking on vascular responsiveness J Appl Physiol, June 1, 2004; 96(6): 2139 - 2145. [Abstract] [Full Text] [PDF]
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E. A. Jaimes, E. G. DeMaster, R.-X. Tian, and L. Raij Stable Compounds of Cigarette Smoke Induce Endothelial Superoxide Anion Production via NADPH Oxidase Activation Arterioscler Thromb Vasc Biol, June 1, 2004; 24(6): 1031 - 1036. [Abstract] [Full Text] [PDF]
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D. P. Faxon, V. Fuster, P. Libby, J. A. Beckman, W. R. Hiatt, R. W. Thompson, J. N. Topper, B. H. Annex, J. H. Rundback, R. P. Fabunmi, et al. Atherosclerotic Vascular Disease Conference: Writing Group III: Pathophysiology Circulation, June 1, 2004; 109(21): 2617 - 2625. [Full Text] [PDF]
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J. A. Ambrose and R. S. Barua The pathophysiology of cigarette smoking and cardiovascular disease: An update J. Am. Coll. Cardiol., May 19, 2004; 43(10): 1731 - 1737. [Abstract] [Full Text] [PDF]
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K. Watts, P. Beye, A. Siafarikas, E. A. Davis, T. W. Jones, G. O'Driscoll, and D. J. Green Exercise training normalizes vascular dysfunction and improves central adiposity in obese adolescents J. Am. Coll. Cardiol., May 19, 2004; 43(10): 1823 - 1827. [Abstract] [Full Text] [PDF]
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C. M Papamichael, K. A Aznaouridis, K. S Stamatelopoulos, E. N Karatzis, A. D Protogerou, T. G Papaioannou, J. P Lekakis, and M. E Mavrikakis Endothelial dysfunction and type of cigarette smoked: the impact of 'light' versus regular cigarette smoking Vascular Medicine, May 1, 2004; 9(2): 103 - 105. [Abstract] [PDF]
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G. N. Thomas, P. Chook, M. Qiao, X. S. Huang, H. C. Leong, D. S. Celermajer, and K. S. Woo Deleterious Impact of "High Normal" Glucose Levels and Other Metabolic Syndrome Components on Arterial Endothelial Function and Intima-Media Thickness in Apparently Healthy Chinese Subjects: The CATHAY Study Arterioscler Thromb Vasc Biol, April 1, 2004; 24(4): 739 - 743. [Abstract] [Full Text] [PDF]
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A. Singhal, T. J. Cole, M. Fewtrell, J. Deanfield, and A. Lucas Is Slower Early Growth Beneficial for Long-Term Cardiovascular Health? Circulation, March 9, 2004; 109(9): 1108 - 1113. [Abstract] [Full Text] [PDF]
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J. C. Yugar-Toledo, J. E. Tanus-Santos, M. Sabha, M. G. Sousa, M. Cittadino, L. H. B. Tacito, and H. Moreno Jr. Uncontrolled Hypertension, Uncompensated Type II Diabetes, and Smoking Have Different Patterns of Vascular Dysfunction Chest, March 1, 2004; 125(3): 823 - 830. [Abstract] [Full Text] [PDF]
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P. Lind, G. Engstrom, L. Stavenow, L. Janzon, F. Lindgarde, and B. Hedblad Risk of Myocardial Infarction and Stroke in Smokers Is Related to Plasma Levels of Inflammation-Sensitive Proteins Arterioscler Thromb Vasc Biol, March 1, 2004; 24(3): 577 - 582. [Abstract] [Full Text] [PDF]
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 F A Sayed-Tabatabaei, A F C Schut, A Hofman, A M Bertoli-Avella, J Vergeer, J C M Witteman, and C M van Duijn A study of gene-environment interaction on the gene for angiotensin converting enzyme: a combined functional and population based approach J. Med. Genet., February 1, 2004; 41(2): 99 - 103. [Abstract] [Full Text] [PDF]
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F. J. Nieto, D. M. Herrington, S. Redline, E. J. Benjamin, and J. A. Robbins Sleep Apnea and Markers of Vascular Endothelial Function in a Large Community Sample of Older Adults Am. J. Respir. Crit. Care Med., February 1, 2004; 169(3): 354 - 360. [Abstract] [Full Text] [PDF]
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 Y. Jang, O. Y. Kim, H. J. Ryu, J. Y. Kim, S. H. Song, J. M. Ordovas, and J. H. Lee Visceral fat accumulation determines postprandial lipemic response, lipid peroxidation, DNA damage, and endothelial dysfunction in nonobese Korean men J. Lipid Res., December 1, 2003; 44(12): 2356 - 2364. [Abstract] [Full Text] [PDF]
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 A. Vychytil, M. Fodinger, J. Pleiner, M. Mullner, P. Konner, S. Skoupy, C. Rohrer, M. Wolzt, and G. Sunder-Plassmann Acute effect of amino acid peritoneal dialysis solution on vascular function Am. J. Clinical Nutrition, November 1, 2003; 78(5): 1039 - 1045. [Abstract] [Full Text] [PDF]
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M. E. Widlansky, N. Gokce, J. F. Keaney Jr, and J. A. Vita The clinical implications of endothelial dysfunction J. Am. Coll. Cardiol., October 1, 2003; 42(7): 1149 - 1160. [Abstract] [Full Text] [PDF]
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K. K. Koh, J. Y. Ahn, D. K. Jin, B.-K. Yoon, H. S. Kim, D. S. Kim, W. C. Kang, S. H. Han, I. S. Choi, and E. K. Shin Significant Differential Effects of Hormone Therapy or Tibolone on Markers of Cardiovascular Disease in Postmenopausal Women: A Randomized, Double-Blind, Placebo-Controlled, Crossover Study Arterioscler Thromb Vasc Biol, October 1, 2003; 23(10): 1889 - 1894. [Abstract] [Full Text] [PDF]
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S. Y. Chan, G. B. J. Mancini, L. Kuramoto, M. Schulzer, J. Frohlich, and A. Ignaszewski The prognostic importance of endothelial dysfunction and carotid atheromaburden in patients with coronary artery disease J. Am. Coll. Cardiol., September 17, 2003; 42(6): 1037 - 1043. [Abstract] [Full Text] [PDF]
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A. Nohria, L. Garrett, W. Johnson, S. Kinlay, P. Ganz, and M. A. Creager Endothelin-1 and Vascular Tone in Subjects With Atherogenic Risk Factors Hypertension, July 1, 2003; 42(1): 43 - 48. [Abstract] [Full Text] [PDF]
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