(Circulation. 2000;101:1899.)
© 2000 American Heart Association, Inc.
Clinical Investigation and Reports |
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
BackgroundEndothelial 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 ResultsCoronary 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.
ConclusionsCoronary 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
This article has been cited by other articles:
![]() |
K. Turkmen, H. Oflaz, B. Uslu, A. O. Cimen, A. Elitok, E. Kasikcioglu, S. Alisir, F. Tufan, S. Namli, M. Uysal, et al. Coronary Flow Velocity Reserve and Carotid Intima Media Thickness in Patients with Autosomal Dominant Polycystic Kidney Disease: From Impaired Tubules to Impaired Carotid and Coronary Arteries Clin. J. Am. Soc. Nephrol., July 1, 2008; 3(4): 986 - 991. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. R. Pries, H. Habazettl, G. Ambrosio, P. R. Hansen, J. C. Kaski, V. Schachinger, H. Tillmanns, G. Vassalli, I. Tritto, M. Weis, et al. A review of methods for assessment of coronary microvascular disease in both clinical and experimental settings Cardiovasc Res, June 25, 2008; (2008) cvn136v2. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. I. Hamilos, M. Ostojic, B. Beleslin, D. Sagic, L. Mangovski, S. Stojkovic, M. Nedeljkovic, D. Orlic, B. Milosavljevic, D. Topic, et al. Differential effects of drug-eluting stents on local endothelium-dependent coronary vasomotion. J. Am. Coll. Cardiol., June 3, 2008; 51(22): 2123 - 2129. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. B. Muhlestein Endothelial dysfunction associated with drug-eluting stents what, where, when, and how? J. Am. Coll. Cardiol., June 3, 2008; 51(22): 2139 - 2140. [Full Text] [PDF] |
||||
![]() |
A. L. Moens, C. J. Vrints, M. J. Claeys, J.-P. Timmermans, H. C. Champion, and D. A. Kass Mechanisms and potential therapeutic targets for folic acid in cardiovascular disease Am J Physiol Heart Circ Physiol, May 1, 2008; 294(5): H1971 - H1977. [Abstract] [Full Text] [PDF] |
||||
![]() |
G. R. Romeo and A. Kazlauskas Oxysterol and Diabetes Activate STAT3 and Control Endothelial Expression of Profilin-1 via OSBP1 J. Biol. Chem., April 11, 2008; 283(15): 9595 - 9605. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. J. Crabtree, C. L. Smith, G. Lam, M. S. Goligorsky, and S. S. Gross Ratio of 5,6,7,8-tetrahydrobiopterin to 7,8-dihydrobiopterin in endothelial cells determines glucose-elicited changes in NO vs. superoxide production by eNOS Am J Physiol Heart Circ Physiol, April 1, 2008; 294(4): H1530 - H1540. [Abstract] [Full Text] [PDF] |
||||
![]() |
V. Stangl, V. Witzel, G. Baumann, and K. Stangl Current diagnostic concepts to detect coronary artery disease in women Eur. Heart J., March 2, 2008; 29(6): 707 - 717. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Terashima, P. K. Nguyen, G. D. Rubin, C. Iribarren, B. K. Courtney, A. S. Go, S. P. Fortmann, and M. V. McConnell Impaired Coronary Vasodilation by Magnetic Resonance Angiography Is Associated With Advanced Coronary Artery Calcification J. Am. Coll. Cardiol. Img., March 1, 2008; 1(2): 167 - 173. [Abstract] [Full Text] [PDF] |
||||
![]() |
N. Reichek and D. Alexander Coronary Artery Function: Out of the Cath Lab and Into the Magnet J. Am. Coll. Cardiol. Img., March 1, 2008; 1(2): 174 - 176. [Full Text] [PDF] |
||||
![]() |
M. R. Vesely and V. Dilsizian Nuclear Cardiac Stress Testing in the Era of Molecular Medicine J. Nucl. Med., March 1, 2008; 49(3): 399 - 413. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. Imamura, R. Takahashi, R. Murakami, H. Kataoka, X. W. Cheng, Y. Numaguchi, T. Murohara, and K. Okumura The effects of endothelial nitric oxide synthase gene polymorphisms on endothelial function and metabolic risk factors in healthy subjects: the significance of plasma adiponectin levels Eur. J. Endocrinol., February 1, 2008; 158(2): 189 - 195. [Abstract] [Full Text] [PDF] |
||||
![]() |
F. Rigo, R. Sicari, S. Gherardi, A. Djordjevic-Dikic, L. Cortigiani, and E. Picano The additive prognostic value of wall motion abnormalities and coronary flow reserve during dipyridamole stress echo Eur. Heart J., January 1, 2008; 29(1): 79 - 88. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. T. Kearney, E. R. Duncan, M. Kahn, and S. B. Wheatcroft Insulin resistance and endothelial cell dysfunction: studies in mammalian models Exp Physiol, January 1, 2008; 93(1): 158 - 163. [Abstract] [Full Text] [PDF] |
||||
![]() |
E. L. Schiffrin Oxidative Stress, Nitric Oxide Synthase, and Superoxide Dismutase: A Matter of Imbalance Underlies Endothelial Dysfunction in the Human Coronary Circulation Hypertension, January 1, 2008; 51(1): 31 - 32. [Full Text] [PDF] |
||||
![]() |
G. P. Joshi, R. Gertler, and R. Fricker Cardiovascular Thromboembolic Adverse Effects Associated with Cyclooxygenase-2 Selective Inhibitors and Nonselective Antiinflammatory Drugs Anesth. Analg., December 1, 2007; 105(6): 1793 - 1804. [Abstract] [Full Text] [PDF] |
||||
![]() |
U. Sen, N. Tyagi, M. Kumar, K. S. Moshal, W. E. Rodriguez, and S. C. Tyagi Cystathionine- -synthase gene transfer and 3-deazaadenosine ameliorate inflammatory response in endothelial cells Am J Physiol Cell Physiol, December 1, 2007; 293(6): C1779 - C1787. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. I. Worthley, R. S. Kanani, Y.-H. Sun, Y. Sun, D. M. Goodhart, M. J. Curtis, and T. J. Anderson Effects of tetrahydrobiopterin on coronary vascular reactivity in atherosclerotic human coronary arteries Cardiovasc Res, December 1, 2007; 76(3): 539 - 546. [Abstract] [Full Text] [PDF] |
||||
![]() |
L. G. Spagnoli, E. Bonanno, G. Sangiorgi, and A. Mauriello Role of Inflammation in Atherosclerosis J. Nucl. Med., November 1, 2007; 48(11): 1800 - 1815. [Abstract] [Full Text] [PDF] |
||||
![]() |
E. R. Duncan, S. J. Walker, V. A. Ezzat, S. B. Wheatcroft, J.-M. Li, A. M. Shah, and M. T. Kearney Accelerated endothelial dysfunction in mild prediabetic insulin resistance: the early role of reactive oxygen species Am J Physiol Endocrinol Metab, November 1, 2007; 293(5): E1311 - E1319. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Briet, C. Collin, S. Laurent, A. Tan, M. Azizi, M. Agharazii, X. Jeunemaitre, F. Alhenc-Gelas, and P. Boutouyrie Endothelial Function and Chronic Exposure to Air Pollution in Normal Male Subjects Hypertension, November 1, 2007; 50(5): 970 - 976. [Abstract] [Full Text] [PDF] |
||||
![]() |
L. Cortigiani, F. Rigo, S. Gherardi, R. Sicari, M. Galderisi, F. Bovenzi, and E. Picano Additional Prognostic Value of Coronary Flow Reserve in Diabetic and Nondiabetic Patients With Negative Dipyridamole Stress Echocardiography by Wall Motion Criteria J. Am. Coll. Cardiol., October 2, 2007; 50(14): 1354 - 1361. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. Philpott and T. J. Anderson Reactive Hyperemia and Cardiovascular Risk Arterioscler. Thromb. Vasc. Biol., October 1, 2007; 27(10): 2065 - 2067. [Full Text] [PDF] |
||||
![]() |
A. L. Huang, A. E. Silver, E. Shvenke, D. W. Schopfer, E. Jahangir, M. A. Titas, A. Shpilman, J. O. Menzoian, M. T. Watkins, J. D. Raffetto, et al. Predictive Value of Reactive Hyperemia for Cardiovascular Events in Patients With Peripheral Arterial Disease Undergoing Vascular Surgery Arterioscler. Thromb. Vasc. Biol., October 1, 2007; 27(10): 2113 - 2119. [Abstract] [Full Text] [PDF] |
||||
![]() |
L. Tiano, R. Belardinelli, P. Carnevali, F. Principi, G. Seddaiu, and G. P. Littarru Effect of coenzyme Q10 administration on endothelial function and extracellular superoxide dismutase in patients with ischaemic heart disease: a double-blind, randomized controlled study Eur. Heart J., September 2, 2007; 28(18): 2249 - 2255. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. de Bree, L. A van Mierlo, and R. Draijer Folic acid improves vascular reactivity in humans: a meta-analysis of randomized controlled trials Am. J. Clinical Nutrition, September 1, 2007; 86(3): 610 - 617. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. Daemen and P. W. Serruys Drug-Eluting Stent Update 2007: Part II: Unsettled Issues Circulation, August 21, 2007; 116(8): 961 - 968. [Full Text] [PDF] |
||||
![]() |
S. M. Shenouda and J. A. Vita Effects of Flavonoid-Containing Beverages and EGCG on Endothelial Function J. Am. Coll. Nutr., August 1, 2007; 26(4): 366S - 372S. [Abstract] [Full Text] [PDF] |
||||
![]() |
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] |
||||
![]() |
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] |
||||
![]() |
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] |
||||
![]() |
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] |
||||
![]() |
T. J. Anderson Prognostic Significance of Brachial Flow-Mediated Vasodilation Circulation, May 8, 2007; 115(18): 2373 - 2375. [Full Text] [PDF] |
||||
![]() |
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] |
||||
![]() |
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] |
||||
![]() |
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] |
||||
![]() |
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] |
||||
![]() |
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] |
||||
![]() |
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] |
||||
![]() |
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] |
||||
![]() |
T. Minamino and M. Hori Protecting endothelial function: A novel therapeutic target of ATP-sensitive potassium channel openers Cardiovasc Res, February 1, 2007; 73(3): 448 - 449. [Full Text] [PDF] |
||||
![]() |
N. Suematsu, C. Ojaimi, S. Kinugawa, Z. Wang, X. Xu, A. Koller MD, F. A. Recchia, and T. H. Hintze Hyperhomocysteinemia Alters Cardiac Substrate Metabolism by Impairing Nitric Oxide Bioavailability Through Oxidative Stress Circulation, January 16, 2007; 115(2): 255 - 262. [Abstract] [Full Text] [PDF] |
||||
![]() |
V. J. Dzau, E. M. Antman, H. R. Black, D. L. Hayes, J. E. Manson, J. Plutzky, J. J. Popma, and W. Stevenson The Cardiovascular Disease Continuum Validated: Clinical Evidence of Improved Patient Outcomes: Part II: Clinical Trial Evidence (Acute Coronary Syndromes Through Renal Disease) and Future Directions Circulation, December 19, 2006; 114(25): 2871 - 2891. [Full Text] [PDF] |
||||
![]() |
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] |
||||
![]() |
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] |
||||
![]() |
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] |
||||
![]() |
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] |
||||
![]() |
R. G. Shaffer, S. Greene, A. Arshi, G. Supple, A. Bantly, J. S Moores, M. S Parmacek, and E. R Mohler III Effect of acute exercise on endothelial progenitor cells in patients with peripheral arterial disease Vascular Medicine, November 1, 2006; 11(4): 219 - 226. [Abstract] [PDF] |
||||
![]() |
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] |
||||
![]() |
A F Leite-Moreira and P Castro-Chaves Heart failure: statins for all? Heart, November 1, 2006; 92(11): 1537 - 1538. [Full Text] [PDF] |
||||
![]() |
S. Wassmann, N. Werner, T. Czech, and G. Nickenig Improvement of Endothelial Function by Systemic Transfusion of Vascular Progenitor Cells Circ. Res., October 13, 2006; 99(8): E74 - E83. [Abstract] [Full Text] [PDF] |
||||
![]() |
W. Koenig, N. Khuseyinova, J. Baumert, C. Meisinger, and H. Lowel Serum Concentrations of Adiponectin and Risk of Type 2 Diabetes Mellitus and Coronary Heart Disease in Apparently Healthy Middle-Aged Men: Results From the 18-Year Follow-Up of a Large Cohort From Southern Germany J. Am. Coll. Cardiol., October 3, 2006; 48(7): 1369 - 1377. [Abstract] [Full Text] [PDF] |
||||
![]() |
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] |
||||
![]() |
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] |
||||
![]() |
A. Geerlings, I. C. Villar, F. H. Zarco, M. Sanchez, R. Vera, A. Z. Gomez, J. Boza, and J. Duarte Identification and characterization of novel Angiotensin-converting enzyme inhibitors obtained from goat milk. J Dairy Sci, September 1, 2006; 89(9): 3326 - 3335. [Abstract] [Full Text] [PDF] |
||||
![]() |
|