(Circulation. 1997;95:1119-1121.)
© 1997 American Heart Association, Inc.
Articles |
Hyperhomocyst(e)inemia Is Associated With Impaired Endothelium-Dependent Vasodilation in Humans
the Vascular Medicine and Atherosclerosis Unit (A.T., T.O., M.G., M.A.C.), Cardiovascular Division, Brigham and Women's Hospital and Harvard Medical School, Boston, Mass, and Associated Regional and University Pathologists, Inc Laboratories (J.T.W.), Salt Lake City, Utah.
Correspondence to Mark A. Creager, MD, Cardiovascular Division, Brigham and Women's Hospital, 75 Francis St, Boston, MA 02115.
Background Hyperhomocyst(e)inemia is a risk factor for atherosclerosis and is prevalent in the elderly. The objective of this study was to determine whether hyperhomocyst(e)inemia is associated with impaired endothelium-dependent vasodilation in humans.
Methods and Results High-resolution vascular ultrasonography was used to study endothelium-dependent and -independent vasodilation in a nonatherosclerotic peripheral conduit artery of 26 elderly hyperhomocyst(e)inemic subjects and 15 age- and sex-matched subjects with normal homocysteine levels. Flow-mediated, endothelium-dependent (nitric oxide–mediated) vasodilation was assessed by measuring the percent change in brachial artery diameter during reactive hyperemia. Endothelium-independent vasodilation was assessed after the administration of 0.4 mg sublingual nitroglycerin. Endothelium-dependent vasodilation was significantly impaired in the hyperhomocyst(e)inemic subjects compared with control subjects (3.7±0.6% versus 8.1±1.2%; P=.004), whereas endothelium-independent vasodilation was not different between the two groups (10.1±1.6% versus 9.3±1.5%; P=NS). In a linear regression analysis with serum homocysteine concentration, folic acid, age, sex, cholesterol (serum total, LDL, or HDL cholesterol), mean arterial blood pressure, use of antihypertensive medication, and baseline brachial artery diameter included as covariates, serum homocysteine concentration emerged as the only significant predictor of flow-mediated vasodilation.
Conclusions These data indicate that hyperhomocyst(e)inemia is associated with impaired endothelium-dependent vasodilation in humans and suggest that the bioavailability of nitric oxide is decreased in hyperhomocyst(e)inemic humans. (. 1997;95:1119-1121.)
Key Words: endothelium • endothelium-derived factors • homocysteine • vasodilation
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 L. Lavie, A. Perelman, and P. Lavie Plasma Homocysteine Levels in Obstructive Sleep Apnea : Association With Cardiovascular Morbidity Chest, September 1, 2001; 120(3): 900 - 908. [Abstract] [Full Text] [PDF]
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N. M. de Roos, M. L. Bots, and M. B. Katan Replacement of Dietary Saturated Fatty Acids by Trans Fatty Acids Lowers Serum HDL Cholesterol and Impairs Endothelial Function in Healthy Men and Women Arterioscler Thromb Vasc Biol, July 1, 2001; 21(7): 1233 - 1237. [Abstract] [Full Text] [PDF]
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 M. Weger, O. Stanger, H. Deutschmann, M. Simon, W. Renner, O. Schmut, J. Semmelrock, and A. Haas Hyperhomocyst(e)inaemia, but not MTHFR C677T mutation, as a risk factor for non-arteritic ischaemic optic neuropathy Br J Ophthalmol, July 1, 2001; 85(7): 803 - 806. [Abstract] [Full Text] [PDF]
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 A. lannuzzi, G. Jannuzzo, C. Sapio, P. Pauciullo, D. Jorio, N. Spampinato, M. Mancini, and P. Rubba L-Arginine Improves Post-Ischemic Vasodilation in Coronary Heart Disease Patients Taking Vasodilating Drugs Journal of Cardiovascular Pharmacology and Therapeutics, June 1, 2001; 6(2): 121 - 127. [Abstract] [PDF]
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 V. Cavalca, G. Cighetti, F. Bamonti, A. Loaldi, L. Bortone, C. Novembrino, M. De Franceschi, R. Belardinelli, and M. D. Guazzi Oxidative Stress and Homocysteine in Coronary Artery Disease Clin. Chem., May 1, 2001; 47(5): 887 - 892. [Abstract] [Full Text] [PDF]
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A. A Brown and F. B Hu Dietary modulation of endothelial function: implications for cardiovascular disease Am. J. Clinical Nutrition, April 1, 2001; 73(4): 673 - 686. [Abstract] [Full Text] [PDF]
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 C G Hanratty, L T McGrath, D F McAuley, I S Young, and G D Johnston The effects of oral methionine and homocysteine on endothelial function Heart, March 1, 2001; 85(3): 326 - 330. [Abstract] [Full Text]
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V. Gallai, V. Caso, M. Paciaroni, G. Cardaioli, E. Arning, T. Bottiglieri, and L. Parnetti Mild Hyperhomocyst(e)inemia : A Possible Risk Factor for Cervical Artery Dissection Stroke, March 1, 2001; 32(3): 714 - 718. [Abstract] [Full Text] [PDF]
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Z. Bagi, Z. Ungvari, L. Szollar, and A. Koller Flow-Induced Constriction in Arterioles of Hyperhomocysteinemic Rats Is Due to Impaired Nitric Oxide and Enhanced Thromboxane A2 Mediation Arterioscler Thromb Vasc Biol, February 1, 2001; 21(2): 233 - 237. [Abstract] [Full Text] [PDF]
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 C. W. Compher, B. P. Kinosian, N. Evans-Stoner, J. Huzinec, and G. P. Buzby Hyperhomocysteinemia Is Associated with Venous Thrombosis in Patients with Short Bowel Syndrome JPEN J Parenter Enteral Nutr, January 1, 2001; 25(1): 1 - 8. [Abstract] [PDF]
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M. Rubenfire, S. Rajagopalan, and L. Mosca Carotid artery vasoreactivity in response to sympathetic stress correlates with coronary disease risk and is independent of wall thickness J. Am. Coll. Cardiol., December 1, 2000; 36(7): 2192 - 2197. [Abstract] [Full Text] [PDF]
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J. Duan, T. Murohara, H. Ikeda, K.-i. Sasaki, S. Shintani, T. Akita, T. Shimada, and T. Imaizumi Hyperhomocysteinemia Impairs Angiogenesis in Response to Hindlimb Ischemia Arterioscler Thromb Vasc Biol, December 1, 2000; 20(12): 2579 - 2585. [Abstract] [Full Text] [PDF]
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J. C. Chambers, P. M. Ueland, O. A. Obeid, J. Wrigley, H. Refsum, and J. S. Kooner Improved Vascular Endothelial Function After Oral B Vitamins : An Effect Mediated Through Reduced Concentrations of Free Plasma Homocysteine Circulation, November 14, 2000; 102(20): 2479 - 2483. [Abstract] [Full Text] [PDF]
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L. M. Title, P. M. Cummings, K. Giddens, J. J. Genest Jr, and B. A. Nassar Effect of folic acid and antioxidant vitamins on endothelial dysfunction in patients with coronary artery disease J. Am. Coll. Cardiol., September 1, 2000; 36(3): 758 - 765. [Abstract] [Full Text] [PDF]
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P. M Ueland, H. Refsum, S. A. Beresford, and S. E. Vollset The controversy over homocysteine and cardiovascular risk Am. J. Clinical Nutrition, August 1, 2000; 72(2): 324 - 332. [Abstract] [Full Text] [PDF]
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S. T. W. Morris, J. J. V. McMurray, R. S. C. Rodger, and A. G. Jardine Impaired endothelium-dependent vasodilatation in uraemia Nephrol. Dial. Transplant., August 1, 2000; 15(8): 1194 - 1200. [Abstract] [Full Text] [PDF]
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T. Omland, A. Samuelsson, M. Hartford, J. Herlitz, T. Karlsson, B. Christensen, and K. Caidahl Serum Homocysteine Concentration as an Indicator of Survival in Patients With Acute Coronary Syndromes Arch Intern Med, June 26, 2000; 160(12): 1834 - 1840. [Abstract] [Full Text] [PDF]
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J Thambyrajah and J.N Townend Homocysteine and atherothrombosis--mechanisms for injury Eur. Heart J., June 2, 2000; 21(12): 967 - 974. [PDF]
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R. H. Boger, S. M. Bode-Boger, K. Sydow, D. D. Heistad, and S. R. Lentz Plasma Concentration of Asymmetric Dimethylarginine, an Endogenous Inhibitor of Nitric Oxide Synthase, Is Elevated in Monkeys With Hyperhomocyst(e)inemia or Hypercholesterolemia Arterioscler Thromb Vasc Biol, June 1, 2000; 20(6): 1557 - 1564. [Abstract] [Full Text] [PDF]
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D. W. Jacobsen Hyperhomocysteinemia and Oxidative Stress : Time for a Reality Check? Arterioscler Thromb Vasc Biol, May 1, 2000; 20(5): 1182 - 1184. [Full Text] [PDF]
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D. E. L. Wilcken, X. L. Wang, T. Adachi, H. Hara, N. Duarte, K. Green, and B. Wilcken Relationship Between Homocysteine and Superoxide Dismutase in Homocystinuria : Possible Relevance to Cardiovascular Risk Arterioscler Thromb Vasc Biol, May 1, 2000; 20(5): 1199 - 1202. [Abstract] [Full Text] [PDF]
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Z. Ungvari, E. Sarkadi-Nagy, Z. Bagi, L. Szollar, and A. Koller Simultaneously Increased TxA2 Activity in Isolated Arterioles and Platelets of Rats With Hyperhomocysteinemia Arterioscler Thromb Vasc Biol, May 1, 2000; 20(5): 1203 - 1208. [Abstract] [Full Text] [PDF]
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K. S. Woo, J. E. Sanderson, Y. Y. Sun, P. Chook, A. S. P. Cheung, L. T. Chan, C. Metreweli, Y. I. Lolin, and D. S. Celermajer Hyperhomocyst(e)inemia Is a Risk Factor for Arterial Endothelial Dysfunction in Humans Circulation, March 28, 2000; 101 (12): e116 - e116. [Full Text] [PDF]
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S. E. Brett, J. M. Ritter, and P. J. Chowienczyk Diastolic Blood Pressure Changes During Exercise Positively Correlate With Serum Cholesterol and Insulin Resistance Circulation, February 15, 2000; 101(6): 611 - 615. [Abstract] [Full Text] [PDF]
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C.-L. Chao, T.-L. Kuo, and Y.-T. Lee Effects of Methionine-Induced Hyperhomocysteinemia on Endothelium-Dependent Vasodilation and Oxidative Status in Healthy Adults Circulation, February 8, 2000; 101(5): 485 - 490. [Abstract] [Full Text] [PDF]
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 M. R. Rinder, R. J. Spina, and A. A. Ehsani Enhanced endothelium-dependent vasodilation in older endurance-trained men J Appl Physiol, February 1, 2000; 88(2): 761 - 766. [Abstract] [Full Text] [PDF]
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K. ROBINSON Homocysteine, B vitamins, and risk of cardiovascular disease Heart, February 1, 2000; 83(2): 127 - 130. [Full Text]
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K. S. Woo, P. Chook, Y. I. Lolin, J. E. Sanderson, C. Metreweli, and D. S. Celermajer Folic acid improves arterial endothelial function in adults with hyperhomocystinemia J. Am. Coll. Cardiol., December 1, 1999; 34(7): 2002 - 2006. [Abstract] [Full Text] [PDF]
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J. C. Chambers, O. A. Obeid, and J. S. Kooner Physiological Increments in Plasma Homocysteine Induce Vascular Endothelial Dysfunction in Normal Human Subjects Arterioscler Thromb Vasc Biol, December 1, 1999; 19(12): 2922 - 2927. [Abstract] [Full Text] [PDF]
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V. Schachinger, M. B. Britten, M. Elsner, D. H. Walter, I. Scharrer, and A. M. Zeiher A Positive Family History of Premature Coronary Artery Disease Is Associated With Impaired Endothelium-Dependent Coronary Blood Flow Regulation Circulation, October 5, 1999; 100(14): 1502 - 1508. [Abstract] [Full Text] [PDF]
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 V. Fonseca, S. C. Guba, and L. M. Fink Hyperhomocysteinemia and the Endocrine System: Implications for Atherosclerosis and Thrombosis Endocr. Rev., October 1, 1999; 20(5): 738 - 759. [Abstract] [Full Text]
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 G. Lupattelli, S. Rufini, E. H. Locati, R. Lombardini, G. Ciuffetti, D. Siepi, E. Mannarino, and G. Lupattelli Hyperhomocyst(e)inemia Is Associated with Carotid Atherosclerosis Angiology, October 1, 1999; 50(10): 823 - 830. [Abstract] [PDF]
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