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Circulation. 2000;101:948-954

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(Circulation. 2000;101:948.)
© 2000 American Heart Association, Inc.


Clinical Investigation and Reports

Long-Term Follow-Up of Patients With Mild Coronary Artery Disease and Endothelial Dysfunction

Jassim Al Suwaidi, MB, ChB; Shuichi Hamasaki, MD; Stuart T. Higano, MD; Rick A. Nishimura, MD; David R. Holmes, Jr, MD; Amir Lerman, MD

From the Center for Coronary Physiology and Imaging, Division of Cardiovascular Diseases, and Department of Internal Medicine, Mayo Clinic and Mayo Foundation, Rochester, Minn.

Correspondence to Amir Lerman, MD, Mayo Clinic, 200 First St SW, Rochester, MN 55905. E-mail lerman.amir{at}mayo.edu

Background—Coronary endothelial dysfunction is characterized by vasoconstrictive response to the endothelium-dependent vasodilator acetylcholine. Although endothelial dysfunction is considered an early phase of coronary atherosclerosis, there is a paucity of information regarding the outcome of these patients. Thus, this study was designed to evaluate the outcome of patients with mild coronary artery disease on the basis of their endothelial function.

Methods and Results—Follow-up was obtained in 157 patients with mildly diseased coronary arteries who had undergone coronary vascular reactivity evaluation by graded administration of intracoronary acetylcholine, adenosine, and nitroglycerin and intracoronary ultrasound at the time of diagnostic study. Patients were divided on the basis of their response to acetylcholine into 3 groups: group 1 (n=83), patients with normal endothelial function; group 2 (n=32), patients with mild endothelial dysfunction; and group 3 (n=42), patients with severe endothelial dysfunction. Over an average 28-month follow-up (range, 11 to 52 months), none of the patients from group 1 or 2 had cardiac events. However, 6 (14%) with severe endothelial dysfunction had 10 cardiac events (P<0.05 versus groups 1 and 2). Cardiac events included myocardial infarction, percutaneous or surgical coronary revascularization, and/or cardiac death.

Conclusions—Severe endothelial dysfunction in the absence of obstructive coronary artery disease is associated with increased cardiac events. This study supports the concept that coronary endothelial dysfunction may play a role in the progression of coronary atherosclerosis.


Key Words: atherosclerosis • acetylcholine • endothelium • coronary disease




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Transgenic expression of human C-reactive protein suppresses endothelial nitric oxide synthase expression and bioactivity after vascular injury
Am J Physiol Heart Circ Physiol, July 1, 2007; 293(1): H489 - H495.
[Abstract] [Full Text] [PDF]


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Diabetes and Vascular Disease ResearchHome page
S. J Hamilton, G. T Chew, and G. F Watts
Therapeutic regulation of endothelial dysfunction in type 2 diabetes mellitus
Diabetes and Vascular Disease Research, June 1, 2007; 4(2): 89 - 102.
[Abstract] [PDF]


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Clin Med ResHome page
V. G. Barauna, K. T. Rosa, M. C. Irigoyen, and E. M. de Oliveira
Effects of Resistance Training on Ventricular Function and Hypertrophy in a Rat Model
Clin. Med. Res., June 1, 2007; 5(2): 114 - 120.
[Abstract] [Full Text] [PDF]


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PediatricsHome page
H. Martin, B. Lindblad, and M. Norman
Endothelial Function in Newborn Infants Is Related to Folate Levels and Birth Weight
Pediatrics, June 1, 2007; 119(6): 1152 - 1158.
[Abstract] [Full Text] [PDF]


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pdiHome page
A. G. Zenovich and D. A. Taylor
CELL THERAPY IN KIDNEY DISEASE: CAUTIOUS OPTIMISM... BUT OPTIMISM NONETHELESS
Perit. Dial. Int., June 1, 2007; 27(Supplement_2): S94 - S103.
[Abstract] [Full Text] [PDF]


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Am. J. Physiol. Heart Circ. Physiol.Home page
N. R. Ferreri
Estrogen-TNF interactions and vascular inflammation
Am J Physiol Heart Circ Physiol, June 1, 2007; 292(6): H2566 - H2569.
[Full Text] [PDF]


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CirculationHome page
S. Lavi, J. P. McConnell, C. S. Rihal, A. Prasad, V. Mathew, L. O. Lerman, and A. Lerman
Local Production of Lipoprotein-Associated Phospholipase A2 and Lysophosphatidylcholine in the Coronary Circulation: Association With Early Coronary Atherosclerosis and Endothelial Dysfunction in Humans
Circulation, May 29, 2007; 115(21): 2715 - 2721.
[Abstract] [Full Text] [PDF]


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CirculationHome page
S. Lavi, A. Prasad, E. H. Yang, V. Mathew, R. D. Simari, C. S. Rihal, L. O. Lerman, and A. Lerman
Smoking Is Associated With Epicardial Coronary Endothelial Dysfunction and Elevated White Blood Cell Count in Patients With Chest Pain and Early Coronary Artery Disease
Circulation, May 22, 2007; 115(20): 2621 - 2627.
[Abstract] [Full Text] [PDF]


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CirculationHome page
T. J. Anderson
Prognostic Significance of Brachial Flow-Mediated Vasodilation
Circulation, May 8, 2007; 115(18): 2373 - 2375.
[Full Text] [PDF]


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J. Appl. Physiol.Home page
P. H. McNulty, B. J. Robertson, M. A. Tulli, J. Hess, L. A. Harach, S. Scott, and L. I. Sinoway
Effect of hyperoxia and vitamin C on coronary blood flow in patients with ischemic heart disease
J Appl Physiol, May 1, 2007; 102(5): 2040 - 2045.
[Abstract] [Full Text] [PDF]


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Eur J EndocrinolHome page
M. V. Jimenez, R. M. Estepa, R. M. Camacho, R. C. Estrada, F. G. Luna, and F. B. Guitarte
Endothelial dysfunction is related to insulin resistance and inflammatory biomarker levels in obese prepubertal children
Eur. J. Endocrinol., April 1, 2007; 156(4): 497 - 502.
[Abstract] [Full Text] [PDF]


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LupusHome page
C. Korkmaz, D.U. Cansu, and T. Kasifoglu
Myocardial infarction in young patients (<=35 years of age) with systemic lupus erythematosus: a case report and clinical analysis of the literature
Lupus, April 1, 2007; 16(4): 289 - 297.
[Abstract] [PDF]


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Eur Heart JHome page
A. Lerman, D. R. Holmes, J. Herrmann, and B. J. Gersh
Microcirculatory dysfunction in ST-elevation myocardial infarction: cause, consequence, or both?
Eur. Heart J., April 1, 2007; 28(7): 788 - 797.
[Abstract] [Full Text] [PDF]


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Arterioscler. Thromb. Vasc. Bio.Home page
U. Landmesser, S. Spiekermann, C. Preuss, S. Sorrentino, D. Fischer, C. Manes, M. Mueller, and H. Drexler
Angiotensin II Induces Endothelial Xanthine Oxidase Activation: Role for Endothelial Dysfunction in Patients With Coronary Disease
Arterioscler Thromb Vasc Biol, April 1, 2007; 27(4): 943 - 948.
[Abstract] [Full Text] [PDF]


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HypertensionHome page
A. Barac, U. Campia, and J. A. Panza
Methods for Evaluating Endothelial Function in Humans
Hypertension, April 1, 2007; 49(4): 748 - 760.
[Full Text] [PDF]


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CirculationHome page
J. E. Deanfield, J. P. Halcox, and T. J. Rabelink
Endothelial Function and Dysfunction: Testing and Clinical Relevance
Circulation, March 13, 2007; 115(10): 1285 - 1295.
[Full Text] [PDF]


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PediatricsHome page
B. Belay, P. F. Belamarich, and C. Tom-Revzon
The Use of Statins in Pediatrics: Knowledge Base, Limitations, and Future Directions
Pediatrics, February 1, 2007; 119(2): 370 - 380.
[Abstract] [Full Text] [PDF]


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JNMHome page
K. Morita, T. Tsukamoto, M. Naya, K. Noriyasu, M. Inubushi, T. Shiga, C. Katoh, Y. Kuge, H. Tsutsui, and N. Tamaki
Smoking Cessation Normalizes Coronary Endothelial Vasomotor Response Assessed with 15O-Water and PET in Healthy Young Smokers
J. Nucl. Med., December 1, 2006; 47(12): 1914 - 1920.
[Abstract] [Full Text] [PDF]


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HeartHome page
K W Lee, A D Blann, K Jolly, G Y H Lip, and on behalf of the BRUM Investigators
Plasma haemostatic markers, endothelial function and ambulatory blood pressure changes with home versus hospital cardiac rehabilitation: the Birmingham Rehabilitation Uptake Maximisation Study
Heart, December 1, 2006; 92(12): 1732 - 1738.
[Abstract] [Full Text] [PDF]


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HypertensionHome page
T. Imanishi, K. Kobayashi, A. Kuroi, S. Mochizuki, M. Goto, K. Yoshida, and T. Akasaka
Effects of Angiotensin II on NO Bioavailability Evaluated Using a Catheter-Type NO Sensor
Hypertension, December 1, 2006; 48(6): 1058 - 1065.
[Abstract] [Full Text] [PDF]


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CirculationHome page
S. Waxman, F. Ishibashi, and J. E. Muller
Detection and Treatment of Vulnerable Plaques and Vulnerable Patients: Novel Approaches to Prevention of Coronary Events
Circulation, November 28, 2006; 114(22): 2390 - 2411.
[Full Text] [PDF]


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DiabetesHome page
W. S. Waring, J. A. McKnight, D. J. Webb, and S. R.J. Maxwell
Uric Acid Restores Endothelial Function in Patients With Type 1 Diabetes and Regular Smokers
Diabetes, November 1, 2006; 55(11): 3127 - 3132.
[Abstract] [Full Text] [PDF]


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EndocrinologyHome page
C. Guo, D. Martinez-Vasquez, G. P. Mendez, M. F. Toniolo, T. M. Yao, E. M. Oestreicher, T. Kikuchi, N. Lapointe, L. Pojoga, G. H. Williams, et al.
Mineralocorticoid Receptor Antagonist Reduces Renal Injury in Rodent Models of Types 1 and 2 Diabetes Mellitus
Endocrinology, November 1, 2006; 147(11): 5363 - 5373.
[Abstract] [Full Text] [PDF]


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HypertensionHome page
C. M. McEniery, S. Wallace, I. S. Mackenzie, B. McDonnell, Yasmin, D. E. Newby, J. R. Cockcroft, and I. B. Wilkinson
Endothelial Function Is Associated With Pulse Pressure, Pulse Wave Velocity, and Augmentation Index in Healthy Humans
Hypertension, October 1, 2006; 48(4): 602 - 608.
[Abstract] [Full Text] [PDF]


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J Am Coll CardiolHome page
G. P. Rossi, G. Maiolino, M. Zanchetta, D. Sticchi, L. Pedon, M. Cesari, D. Montemurro, R. De Toni, S. Zavattiero, and A. C. Pessina
The T-786C Endothelial Nitric Oxide Synthase Genotype Predicts Cardiovascular Mortality in High-Risk Patients
J. Am. Coll. Cardiol., September 19, 2006; 48(6): 1166 - 1174.
[Abstract] [Full Text] [PDF]


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CirculationHome page
K. M. Maki-Petaja, F. C. Hall, A. D. Booth, S. M.L. Wallace, Yasmin, P. W.P. Bearcroft, S. Harish, A. Furlong, C. M. McEniery, J. Brown, et al.
Rheumatoid Arthritis Is Associated With Increased Aortic Pulse-Wave Velocity, Which Is Reduced by Anti-Tumor Necrosis Factor-{alpha} Therapy
Circulation, September 12, 2006; 114(11): 1185 - 1192.
[Abstract] [Full Text] [PDF]