(Circulation. 2000;101:1899.)
© 2000 American Heart Association, Inc.
Clinical Investigation and Reports |
Prognostic Impact of Coronary Vasodilator Dysfunction on Adverse Long-Term Outcome of Coronary Heart Disease
From the Department of Internal Medicine IV, Division of Cardiology, J.W. Goethe University, Frankfurt, Germany.
Correspondence to Volker Schächinger, MD, Department of Internal Medicine IV, Division of Cardiology, J.W. Goethe University, Theodor-Stern-Kai 7, D-60590 Frankfurt, Germany. E-mail schaechinger{at}em.uni-frankfurt.de
Background—Endothelial vasodilator dysfunction is a characteristic feature of patients at risk for coronary atherosclerosis. Therefore, we prospectively investigated whether coronary endothelial dysfunction predicts disease progression and cardiovascular event rates.
Methods and Results—Coronary vasoreactivity was assessed in 147 patients using the endothelium-dependent dilator acetylcholine, sympathetic activation by cold pressor testing, dilator responses to increased blood flow, and dilation in response to nitroglycerin. Cardiovascular events (cardiovascular death, unstable angina, myocardial infarction, percutaneous transluminal coronary angioplasty, coronary bypass grafting, ischemic stroke, or peripheral artery revascularization) served as outcome variables over a median follow-up period of 7.7 years. Patients suffering from cardiovascular events during follow-up (n=16) had significantly increased vasoconstrictor responses to acetylcholine infusion (P=0.009) and cold pressor testing (P=0.002), as well as significantly blunted vasodilator responses to increased blood flow (P<0.001) and the intracoronary injection of nitroglycerin (P=0.001). Impaired endothelial and endothelium-independent coronary vasoreactivity were associated with a significantly higher incidence of cardiovascular events by Kaplan-Meier analysis. By multivariate analysis, all tests of coronary vasoreactivity were significant, independent predictors of a poor prognosis, even after adjustment for traditional cardiovascular risk factors or the presence of atherosclerosis itself.
Conclusions—Coronary endothelial vasodilator dysfunction predicts long-term atherosclerotic disease progression and cardiovascular event rates. Thus, the assessment of coronary endothelial vasoreactivity can provide pivotal information as both a diagnostic and prognostic tool in patients at risk for coronary heart disease.
Key Words: coronary disease • endothelium • prognosis • acetylcholine • myocardial infarction
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Authors/Task Force Members, J.-P. Bassand, C. W. Hamm, D. Ardissino, E. Boersma, A. Budaj, F. Fernandez-Aviles, K. A.A. Fox, D. Hasdai, E. M. Ohman, et al. Guidelines for the diagnosis and treatment of non-ST-segment elevation acute coronary syndromes: The Task Force for the Diagnosis and Treatment of Non-ST-Segment Elevation Acute Coronary Syndromes of the European Society of Cardiology Eur. Heart J., July 1, 2007; 28(13): 1598 - 1660. [Full Text] [PDF]
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F. Nietlispach, B. Julius, R. Schindler, A. Bernheim, C. Binkert, W. Kiowski, and H. P. Brunner-La Rocca Influence of Acute and Chronic Mineralocorticoid Excess on Endothelial Function in Healthy Men Hypertension, July 1, 2007; 50(1): 82 - 88. [Abstract] [Full Text] [PDF]
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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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R. M Cubbon, A. Rajwani, and S. B Wheatcroft The impact of insulin resistance on endothelial function, progenitor cells and repair Diabetes and Vascular Disease Research, June 1, 2007; 4(2): 103 - 111. [Abstract] [PDF]
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M. Lorenz, K. Stangl, and V. Stangl Tea without milk: lifestyle advice based on a small lab study: reply Eur. Heart J., June 1, 2007; 28(11): 1398 - 1399. [Full Text] [PDF]
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 R. E. Schmieder, C. Delles, A. Mimran, J. P. Fauvel, and L. M. Ruilope Impact of Telmisartan Versus Ramipril on Renal Endothelial Function in Patients With Hypertension and Type 2 Diabetes Diabetes Care, June 1, 2007; 30(6): 1351 - 1356. [Abstract] [Full Text] [PDF]
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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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H. Viswambharan, J. M. Carvas, V. Antic, A. Marecic, C. Jud, C. E. Zaugg, X.-F. Ming, J.-P. Montani, U. Albrecht, and Z. Yang Mutation of the Circadian Clock Gene Per2 Alters Vascular Endothelial Function Circulation, April 24, 2007; 115(16): 2188 - 2195. [Abstract] [Full Text] [PDF]
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 R. J. Bisoendial, J. J. P. Kastelein, S. L. M. Peters, J. H. M. Levels, R. Birjmohun, J. I. Rotmans, D. Hartman, J. C. M. Meijers, M. Levi, and E. S. G. Stroes Effects of CRP infusion on endothelial function and coagulation in normocholesterolemic and hypercholesterolemic subjects J. Lipid Res., April 1, 2007; 48(4): 952 - 960. [Abstract] [Full Text] [PDF]
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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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C. Murphy, G. S. Kanaganayagam, B. Jiang, P. J. Chowienczyk, R. Zbinden, M. Saha, S. Rahman, A. M. Shah, M. S. Marber, and M. T. Kearney Vascular Dysfunction and Reduced Circulating Endothelial Progenitor Cells in Young Healthy UK South Asian Men Arterioscler Thromb Vasc Biol, April 1, 2007; 27(4): 936 - 942. [Abstract] [Full Text] [PDF]
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Y. Hattori, S. Hattori, X. Wang, H. Satoh, N. Nakanishi, and K. Kasai Oral Administration of Tetrahydrobiopterin Slows the Progression of Atherosclerosis in Apolipoprotein E-Knockout Mice Arterioscler Thromb Vasc Biol, April 1, 2007; 27(4): 865 - 870. [Abstract] [Full Text] [PDF]
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Z. Yang, K. Venardos, E. Jones, B. J. Morris, J. Chin-Dusting, and D. M. Kaye Identification of a Novel Polymorphism in the 3'UTR of the L-Arginine Transporter Gene SLC7A1: Contribution to Hypertension and Endothelial Dysfunction Circulation, March 13, 2007; 115(10): 1269 - 1274. [Abstract] [Full Text] [PDF]
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 A. K. Nightingale, J. G. Crilley, N. C. Pegge, E. A. Boehm, C. Mumford, D. J. Taylor, P. Styles, K. Clarke, and M. P. Frenneaux Chronic oral ascorbic acid therapy worsens skeletal muscle metabolism in patients with chronic heart failure Eur J Heart Fail, March 1, 2007; 9(3): 287 - 291. [Abstract] [Full Text] [PDF]
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J. T. Kuvin, A. Mammen, P. Mooney, A. A. Alsheikh-Ali, and R. H. Karas Assessment of peripheral vascular endothelial function in the ambulatory setting Vascular Medicine, February 1, 2007; 12(1): 13 - 16. [Abstract] [PDF]
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