(Circulation. 2001;104:191.)
© 2001 American Heart Association, Inc.
Clinical Investigation and Reports |
Prognostic Significance of Endothelial Dysfunction in Hypertensive Patients
From the Internal Medicine and Cardiovascular Diseases Unit (F.P., R.C., A.P, G.V., S.I., A.S., A.F.) and Cardiovascular Surgery Unit (M.C., P.M.), Department of Medicina Sperimentale e Clinica "G. Salvatore," University of Catanzaro Magna Græcia, Catanzaro, Italy, and Cardiologia e Fisiopatologia Cardiovascolare (P.V.) and Medicina Interna (G.S.), Angiologia e Malattie da Arteriosclerosi, University of Perugia, Perugia, Italy.
Correspondence to Francesco Perticone, MD, Department of Medicina Sperimentale e Clinica, Policlinico Mater Domini, Via Tommaso Campanella, 88100 Catanzaro, Italy. E-mail perticone{at}unicz.it
Background—— Forearm endothelial dysfunction, characterized by an impaired vasodilating response to acetylcholine (ACh), may be associated with several cardiovascular risk factors, including essential hypertension. Although the prognostic value of coronary endothelial dysfunction has been demonstrated, that of forearm endothelial dysfunction is still unknown.
Methods and Results—— Endothelium-dependent and -independent vasodilation was investigated in 225 never-treated hypertensive patients (age, 35 to 54 years) by intra-arterial infusion of increasing doses of ACh and sodium nitroprusside. Patients were divided into tertiles on the basis of their increase in ACh-stimulated forearm blood flow (FBF) from basal: group 1, from 30% to 184%; group 2, from 185% to 333%; and group 3, from 339% to 760% increase from basal. During a mean follow-up of 31.5 of months (range, 4 to 84 months), there were 29 major adverse events at the cardiac (n=19), cerebrovascular (n=9), or peripheral vascular (n=1) level. Events included myocardial infarction, angina, coronary revascularization procedures, stroke, transient cerebral ischemic attack, and aortoiliac occlusive disease. Event rate per 100 patient-years was 8.17, 4.34, and 2.02 in the first, second, and third tertiles of peak percent increase in FBF during ACh infusion. The excess risk associated with an FBF increase in the first tertile was significant (relative risk, 2.084; 95% CI, 1.25 to 3.48; P=0.0049) after controlling for individual risk markers, including 24-hour ambulatory blood pressure.
Conclusions—— Our data suggest that forearm endothelial dysfunction is a marker of future cardiovascular events in patients with essential hypertension.
Key Words: endothelium • cardiovascular diseases • hypertension
This article has been cited by other articles:
 |
|
 |
|
  A. Bobik Apolipoprotein CIII and Atherosclerosis: Beyond Effects on Lipid Metabolism Circulation, August 12, 2008; 118(7): 702 - 704. [Full Text] [PDF]
|
|
|
|
 |
|
 F. Perticone, A. Sciacqua, M. Perticone, I. Laino, S. Miceli, I. Care', G. Galiano Leone, F. Andreozzi, R. Maio, and G. Sesti Low-Plasma Insulin-Like Growth Factor-I Levels Are Associated with Impaired Endothelium-Dependent Vasodilatation in a Cohort of Untreated, Hypertensive Caucasian Subjects J. Clin. Endocrinol. Metab., July 1, 2008; 93(7): 2806 - 2810. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. L. Pierce, S. D. Beske, B. R. Lawson, K. L. Southall, F. J. Benay, A. J. Donato, and D. R. Seals Weight Loss Alone Improves Conduit and Resistance Artery Endothelial Function in Young and Older Overweight/Obese Adults Hypertension, July 1, 2008; 52(1): 72 - 79. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. D. Seddon, P. J. Chowienczyk, S. E. Brett, B. Casadei, and A. M. Shah Neuronal Nitric Oxide Synthase Regulates Basal Microvascular Tone in Humans In Vivo Circulation, April 15, 2008; 117(15): 1991 - 1996. [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]
|
|
|
|
 |
|
 F. Perticone, R. Maio, A. Sciacqua, F. Andreozzi, G. Iemma, M. Perticone, C. Zoccali, and G. Sesti Endothelial Dysfunction and C-Reactive Protein Are Risk Factors for Diabetes in Essential Hypertension Diabetes, January 1, 2008; 57(1): 167 - 171. [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]
|
|
|
|
 |
|
 Y.-H. Chan, K.-K. Lau, K.-H. Yiu, S.-W. Li, H.-T. Chan, S. Tam, X.-O. Shu, C.-P. Lau, and H.-F. Tse Isoflavone intake in persons at high risk of cardiovascular events: implications for vascular endothelial function and the carotid atherosclerotic burden Am. J. Clinical Nutrition, October 1, 2007; 86(4): 938 - 945. [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]
|
|
|
|
 |
|
 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]
|
|
|
|
 |
|
 E. Zittan, M. Preis, I. Asmir, A. Cassel, N. Lindenfeld, S. Alroy, D. A. Halon, B. S. Lewis, A. Shiran, J. E. Schliamser, et al. High frequency of vitamin B12 deficiency in asymptomatic individuals homozygous to MTHFR C677T mutation is associated with endothelial dysfunction and homocysteinemia Am J Physiol Heart Circ Physiol, July 1, 2007; 293(1): H860 - H865. [Abstract] [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]
|
|
|
|
|
|
J. Yeboah, J. R. Crouse, F.-C. Hsu, G. L. Burke, and D. M. Herrington Brachial Flow-Mediated Dilation Predicts Incident Cardiovascular Events in Older Adults: The Cardiovascular Health Study Circulation, May 8, 2007; 115(18): 2390 - 2397. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
 |
|
 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]
|
|
|
|
|
|
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]
|
|
|
|
 |
|
 C. J. Boos, G. Y.H. Lip, and A. D. Blann Circulating Endothelial Cells in Cardiovascular Disease J. Am. Coll. Cardiol., October 17, 2006; 48(8): 1538 - 1547. [Abstract] [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]
|
|
|
|
|
|
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]
|
|
|
|
|
|
M. Feletou and P. M. Vanhoutte Endothelial dysfunction: a multifaceted disorder (The Wiggers Award Lecture) Am J Physiol Heart Circ Physiol, September 1, 2006; 291(3): H985 - H1002. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. J Roman, T. Z Naqvi, J. M Gardin, M. Gerhard-Herman, M. Jaff, and E. Mohler American Society of Echocardiography Report: Clinical application of noninvasive vascular ultrasound in cardiovascular risk stratification: a report from the American Society of Echocardiography and the Society for Vascular Medicine and Biology Vascular Medicine, August 1, 2006; 11(3): 201 - 211. [PDF]
|
|
|
|
|
|
W.-Z. Zhang, K. Venardos, J. Chin-Dusting, and D. M. Kaye Adverse Effects of Cigarette Smoke on NO Bioavailability: Role of Arginine Metabolism and Oxidative Stress Hypertension, August 1, 2006; 48(2): 278 - 285. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A Dagre, J Lekakis, C Mihas, A Protogerou, L Thalassinou, D Tryfonopoulos, G Douridas, C Papamichael, and M Alevizaki Association of dehydroepiandrosterone-sulfate with endothelial function in young women with polycystic ovary syndrome. Eur. J. Endocrinol., June 1, 2006; 154(6): 883 - 890. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. S. Vasan Biomarkers of Cardiovascular Disease: Molecular Basis and Practical Considerations Circulation, May 16, 2006; 113(19): 2335 - 2362. [Full Text] [PDF]
|
|
|
|
 |
|
 C. Zoccali, R. Maio, F. Mallamaci, G. Sesti, and F. Perticone Uric Acid and Endothelial Dysfunction in Essential Hypertension J. Am. Soc. Nephrol., May 1, 2006; 17(5): 1466 - 1471. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. A. Elesber, H. Solomon, R. J. Lennon, V. Mathew, A. Prasad, G. Pumper, R. E. Nelson, J. P. McConnell, L. O. Lerman, and A. Lerman Coronary endothelial dysfunction is associated with erectile dysfunction and elevated asymmetric dimethylarginine in patients with early atherosclerosis Eur. Heart J., April 1, 2006; 27(7): 824 - 831. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D Tousoulis, M Charakida, and C Stefanadis Endothelial function and inflammation in coronary artery disease Heart, April 1, 2006; 92(4): 441 - 444. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Zoccali Endothelial Dysfunction and the Kidney: Emerging Risk Factors for Renal Insufficiency and Cardiovascular Outcomes in Essential Hypertension. J. Am. Soc. Nephrol., April 1, 2006; 17(4_suppl_2): S61 - S63. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
U. Campia, L. A. Matuskey, and J. A. Panza Peroxisome Proliferator-Activated Receptor-{gamma} Activation With Pioglitazone Improves Endothelium-Dependent Dilation in Nondiabetic Patients With Major Cardiovascular Risk Factors Circulation, February 14, 2006; 113(6): 867 - 875. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. N. Bairey Merz, L. J. Shaw, S. E. Reis, V. Bittner, S. F. Kelsey, M. Olson, B. D. Johnson, C. J. Pepine, S. Mankad, B. L. Sharaf, et al. Insights From the NHLBI-Sponsored Women's Ischemia Syndrome Evaluation (WISE) Study: Part II: Gender Differences in Presentation, Diagnosis, and Outcome With Regard to Gender-Based Pathophysiology of Atherosclerosis and Macrovascular and Microvascular Coronary Disease J. Am. Coll. Cardiol., February 7, 2006; 47(3_Suppl_S): S21 - S29. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. L. Diez-Marques, M. P. Ruiz-Torres, M. Griera, S. Lopez-Ongil, M. Saura, D. Rodriguez-Puyol, and M. Rodriguez-Puyol Arg-Gly-Asp (RGD)-containing peptides increase soluble guanylate cyclase in contractile cells Cardiovasc Res, February 1, 2006; 69(2): 359 - 369. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Sahin, C. Arslan, M. Naziroglu, S. E. Tunc, M. Demirci, R. Sutcu, and N. Yilmaz Asymmetric Dimethylarginine and Nitric Oxide Levels as Signs of Endothelial Dysfunction in Behcet's Disease Ann. Clin. Lab. Sci., January 1, 2006; 36(4): 449 - 454. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. M. Thule, A. G. Campbell, D. J. Kleinhenz, D. E. Olson, J. J. Boutwell, R. L. Sutliff, and C. M. Hart Hepatic insulin gene therapy prevents deterioration of vascular function and improves adipocytokine profile in STZ-diabetic rats Am J Physiol Endocrinol Metab, January 1, 2006; 290(1): E114 - E122. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. J. Oliver, D. J. Webb, and D. E. Newby Stimulated Tissue Plasminogen Activator Release as a Marker of Endothelial Function in Humans Arterioscler. Thromb. Vasc. Biol., December 1, 2005; 25(12): 2470 - 2479. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Noda, H. Iso, H. Toyoshima, C. Date, A. Yamamoto, S. Kikuchi, A. Koizumi, T. Kondo, Y. Watanabe, Y. Wada, et al. Walking and Sports Participation and Mortality From Coronary Heart Disease and Stroke J. Am. Coll. Cardiol., November 1, 2005; 46(9): 1761 - 1767. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Lind, N. Fors, J. Hall, K. Marttala, and A. Stenborg A Comparison of Three Different Methods to Evaluate Endothelium-Dependent Vasodilation in the Elderly: The Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) Study Arterioscler. Thromb. Vasc. Biol., November 1, 2005; 25(11): 2368 - 2375. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Dell'Omo, G. Penno, S. Del Prato, and R. Pedrinelli Chlorthalidone Improves Endothelial-Mediated Vascular Responses in Hypertension Complicated by Nondiabetic Metabolic Syndrome Journal of Cardiovascular Pharmacology and Therapeutics, October 1, 2005; 10(4): 265 - 272. [Abstract] [PDF]
|
|
|
|
|
|
L C Jones and A D Hingorani Genetic regulation of endothelial function Heart, October 1, 2005; 91(10): 1275 - 1277. [Full Text] [PDF]
|
|
|
|
|
|
J A Vita Endothelial function and clinical outcome Heart, October 1, 2005; 91(10): 1278 - 1279. [Full Text] [PDF]
|
|
|
|
|
|
S. J. Duffy, E. S. Biegelsen, R. T. Eberhardt, D. F. Kahn, B. A. Kingwell, and J. A. Vita Low-Renin Hypertension With Relative Aldosterone Excess Is Associated With Impaired NO-Mediated Vasodilation Hypertension, October 1, 2005; 46(4): 707 - 713. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Meyer, D. Mortl, K. Strecker, M. Hulsmann, V. Kulemann, T. Neunteufl, R. Pacher, and R. Berger Flow-Mediated Vasodilation Predicts Outcome in Patients With Chronic Heart Failure: Comparison With B-Type Natriuretic Peptide J. Am. Coll. Cardiol., September 20, 2005; 46(6): 1011 - 1018. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. S. Najjar, A. Scuteri, and E. G. Lakatta Arterial Aging: Is It an Immutable Cardiovascular Risk Factor? Hypertension, September 1, 2005; 46(3): 454 - 462. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Oechslin, W. Kiowski, R. Schindler, A. Bernheim, B. Julius, and H. P. Brunner-La Rocca Systemic Endothelial Dysfunction in Adults With Cyanotic Congenital Heart Disease Circulation, August 23, 2005; 112(8): 1106 - 1112. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Sherwood, A. L. Hinderliter, L. L. Watkins, R. A. Waugh, and J. A. Blumenthal Impaired Endothelial Function in Coronary Heart Disease Patients With Depressive Symptomatology J. Am. Coll. Cardiol., August 16, 2005; 46(4): 656 - 659. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Neishi, S. Mochizuki, T. Miyasaka, T. Kawamoto, T. Kume, R. Sukmawan, M. Tsukiji, Y. Ogasawara, F. Kajiya, T. Akasaka, et al. Evaluation of bioavailability of nitric oxide in coronary circulation by direct measurement of plasma nitric oxide concentration PNAS, August 9, 2005; 102(32): 11456 - 11461. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Perticone, A. Sciacqua, R. Maio, M. Perticone, R. Maas, R. H. Boger, G. Tripepi, G. Sesti, and C. Zoccali Asymmetric Dimethylarginine, L-Arginine, and Endothelial Dysfunction in Essential Hypertension J. Am. Coll. Cardiol., August 2, 2005; 46(3): 518 - 523. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. A. Potenza, F. L. Marasciulo, D. M. Chieppa, G. S. Brigiani, G. Formoso, M. J. Quon, and M. Montagnani Insulin resistance in spontaneously hypertensive rats is associated with endothelial dysfunction characterized by imbalance between NO and ET-1 production Am J Physiol Heart Circ Physiol, August 1, 2005; 289(2): H813 - H822. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. L. Moens, I. Goovaerts, M. J. Claeys, and C. J. Vrints Flow-Mediated Vasodilation: A Diagnostic Instrument, or an Experimental Tool? Chest, June 1, 2005; 127(6): 2254 - 2263. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A D Gavin and A D Struthers Allopurinol reduces B-type natriuretic peptide concentrations and haemoglobin but does not alter exercise capacity in chronic heart failure Heart, June 1, 2005; 91(6): 749 - 753. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Mittermayer, G. Schaller, J. Pleiner, A. Vychytil, G. Sunder-Plassmann, W. H. Horl, and M. Wolzt Asymmetrical Dimethylarginine Plasma Concentrations Are Related to Basal Nitric Oxide Release but Not Endothelium-Dependent Vasodilation of Resistance Arteries in Peritoneal Dialysis Patients J. Am. Soc. Nephrol., June 1, 2005; 16(6): 1832 - 1838. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Sciacqua, A. Scozzafava, A. Pujia, R. Maio, F. Borrello, F. Andreozzi, M. Vatrano, S. Cassano, M. Perticone, G. Sesti, et al. Interaction between vascular dysfunction and cardiac mass increases the risk of cardiovascular outcomes in essential hypertension Eur. Heart J., May 1, 2005; 26(9): 921 - 927. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. A. Blumenthal, A. Sherwood, M. A. Babyak, L. L. Watkins, R. Waugh, A. Georgiades, S. L. Bacon, J. Hayano, R. E. Coleman, and A. Hinderliter Effects of Exercise and Stress Management Training on Markers of Cardiovascular Risk in Patients With Ischemic Heart Disease: A Randomized Controlled Trial JAMA, April 6, 2005; 293(13): 1626 - 1634. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Passauer, F. Pistrosch, E. Bussemaker, G. Lassig, K. Herbrig, and P. Gross Reduced Agonist-Induced Endothelium-Dependent Vasodilation in Uremia Is Attributable to an Impairment of Vascular Nitric Oxide J. Am. Soc. Nephrol., April 1, 2005; 16(4): 959 - 965. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Natali, E. Toschi, S. Baldeweg, A. Casolaro, S. Baldi, A. M. Sironi, J. S. Yudkin, and E. Ferrannini Haematocrit, type 2 diabetes, and endothelium-dependent vasodilatation of resistance vessels Eur. Heart J., March 1, 2005; 26(5): 464 - 471. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. K. Kharbanda, S. Wallace, B. Walton, A. Donald, J. M. Cross, and J. Deanfield Systemic Acyl-CoA:Cholesterol Acyltransferase Inhibition Reduces Inflammation and Improves Vascular Function in Hypercholesterolemia Circulation, February 15, 2005; 111(6): 804 - 807. [Abstract] [Full Text] [PDF]
|
|
|
|