Online Appendix for the following June 21 JACC article TITLE: Is the Association Between Flow-Mediated Dilation and Cardiovascular Risk Limited to Low-Risk Populations? AUTHORS: Daniel R. Witte, MD, PhD, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands, J. Westerink, MD, Department of Internal Medicine, Section of Vascular Medicine, Diabetes and Endocrinology, University Medical Center Utrecht, Utrecht, the Netherlands, Eelco J. de Koning, MD, PhD, Department of Internal Medicine, Section of Vascular Medicine, Diabetes and Endocrinology, University Medical Center Utrecht, Utrecht, the Netherlands, and the Department of Internal Medicine, Section of Nephrology, Leids University Medical Center, Leiden, the Netherlands, Yolanda van der Graaf, MD, PhD, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands, Diederick E. Grobbee, MD, PhD, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands, Michiel L. Bots, MD, PhD, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands APPENDIX References: Meta-Analysis 1. Zhang X, Zhao SP, Li XP, Gao M, Zhou QC. Endothelium-dependent and - independent functions are impaired in patients with coronary heart disease. Atherosclerosis 2000;149:19–24. 2. Hashimoto M, Akishita M, Eto M, et al. Modulation of endothelium- dependent flow-mediated dilatation of the brachial artery by sex and menstrual cycle. Circulation 1995;92:3431–5. 3. Lekakis J, Mavrikakis M, Papamichael C, et al. Short-term estrogen administration improves abnormal endothelial function in women with systemic sclerosis and Raynaud’s phenomenon. Am Heart J. 1998;136:905–12. 4. Chambers JC, Ueland PM, Obeid OA, Wrigley J, Refsum H, Kooner JS. Improved vascular endothelial function after oral B vitamins: an effect mediated through reduced concentrations of free plasma homocysteine. Circulation 2000;102:2479–83. 5. Lambert J, Aarsen M, Donker AJ, Stehouwer CD. Endothelium-dependent and -independent vasodilation of large arteries in normoalbuminuric insulin-dependent diabetes mellitus. Arterioscler Thromb Vasc Biol 1996;16:705–11. 6. Celermajer DS, Adams MR, Clarkson P, et al. Passive smoking and impaired endothelium-dependent arterial dilatation in healthy young adults. N Engl J Med 1996;334:150–4. 7. McCrohon JA, Adams MR, McCredie RJ, et al. Hormone replacement therapy is associated with improved arterial physiology in healthy post-menopausal women. Clin Endocrinol (Oxf) 1996;45:435–41. 8. Simons LA, von Konigsmark M, Simons J, Stocker R, Celermajer DS. Vitamin E ingestion does not improve arterial endothelial dysfunction in older adults. Atherosclerosis 1999;143:193–9. 9. Chambers JC, McGregor A, Jean-Marie J, Obeid OA, Kooner JS. Demonstration of rapid onset vascular endothelial dysfunction after hyperhomocysteinemia: an effect reversible with vitamin C therapy. Circulation 1999;99:1156–60. 10. Raitakari OT, Adams MR, Celermajer DS. Effect of Lp(a) on the early functional and structural changes of atherosclerosis. Arterioscler Thromb Vasc Biol 1999;19:990–5. 11. Koh KK, Kang MH, Jin DK, et al. Vascular effects of estrogen in type II diabetic postmenopausal women. J Am Coll Cardiol 2001;38:1409–15. 12. Plotnick GD, Corretti MC, Vogel RA. Effect of antioxidant vitamins on the transient impairment of endothelium-dependent brachial artery vasoactivity following a single high-fat meal. JAMA 1997;278:1682–6. 13. Vogel RA, Corretti MC, Plotnick GD. Changes in flow-mediated brachial artery vasoactivity with lowering of desirable cholesterol levels in healthy middleaged men. Am J Cardiol 1996;77:37–40. 14. Toikka JO, Ahotupa M, Viikari JS, et al. Constantly low HDL-cholesterol concentration relates to endothelial dysfunction and increased in vivo LDL-oxidation in healthy young men. Atherosclerosis 1999;147:133–8. 15. de Valk-de Roo GW, Stehouwer CD, Lambert J, et al. Plasma homocysteine is weakly correlated with plasma endothelin and von Willebrand factor but not with endothelium-dependent vasodilatation in healthy postmenopausal women. Clin Chem 1999;45:1200–5. 16. McFarlane R, McCredie RJ, Bonney MA, et al. Angiotensin converting enzyme inhibition and arterial endothelial function in adults with type 1 diabetes mellitus. Diabet Med 1999;16:62–6. 17. Dupuis J, Tardif JC, Cernacek P, Theroux P. Cholesterol reduction rapidly improves endothelial function after acute coronary syndromes. The RECIFE (Reduction of Cholesterol in Ischemia and Function of the Endothelium) trial. Circulation 1999;99:3227–33. 18. Etsuda H, Takase B, Uehata A, et al. Morning attenuation of endothelium- dependent, flow-mediated dilation in healthy young men: possible connection to morning peak of cardiac events? Clin Cardiol 1999;22:417–21. 19. Celermajer DS, Sorensen KE, Georgakopoulos D, et al. Cigarette smoking is associated with dose-related and potentially reversible impairment of endotheliumdependent dilation in healthy young adults. Circulation 1993;88:2149–55. 20. Bae JH, Bassenge E, Kim KB, et al. Postprandial hypertriglyceridemia impairs endothelial function by enhanced oxidant stress. Atherosclerosis 2001;155:517–23. 21. Anderson RA, Evans ML, Ellis GR, et al. The relationships between post– prandial lipaemia, endothelial function and oxidative stress in healthy individuals and patients with type 2 diabetes. Atherosclerosis 2001;154:475–83. 22. Marchesi S, Lupattelli G, Schillaci G, et al. Impaired flow-mediated vasoactivity during post-prandial phase in young healthy men. Atherosclerosis 2000;153:397–402. 23. Wilmink HW, de Kleijn MJ, Bots ML, et al. Lipoprotein (a) is associated with endothelial function 2000;153:249–54. in healthy postmenopausal women. Atherosclerosis 24. Patel AR, Kuvin JT, Pandian NG, et al. Heart failure etiology affects peripheral vascular endothelial function after cardiac transplantation. J Am Coll Cardiol 2001;37:195–200. 25. Raitakari OT, Lai N, Griffiths K, McCredie R, Sullivan D, Celermajer DS. Enhanced peripheral vasodilation in humans after a fatty meal. J Am Coll Cardiol 2000;36:417–22. 26. Sader MA, Griffiths KA, McCredie RJ, Handelsman DJ, Celermajer DS. Androgenic anabolic steroids and arterial structure and function in male bodybuilders. J Am Coll Cardiol 2001;37:224–30. 27. Thambyrajah J, Landray MJ, Jones HJ, McGlynn FJ, Wheeler DC, Townend JN. A randomized double-blind placebo-controlled trial of the effect of homocysteinelowering therapy with folic acid on endothelial function in patients with coronary artery disease. J Am Coll Cardiol 2001;37:1858–63. 28. Woo KS, Chook P, Leong HC, Huang XS, Celermajer DS. The impact of heavy passive smoking on arterial endothelial function in modernized Chinese. J Am Coll Cardiol 2000;36:1228–32. 29. Anderson TJ, Elstein E, Haber H, Charbonneau F. Comparative study of ACE- inhibition, angiotensin II antagonism, and calcium channel blockade on flowmediated vasodilation in patients with coronary disease (BANFF study). J Am Coll Cardiol 2000;35:60–6. 30. Title LM, Cummings PM, Giddens K, Nassar BA. Oral glucose loading acutely attenuates endothelium-dependent vasodilation in healthy adults without diabetes: an effect prevented by vitamins C and E. J Am Coll Cardiol 2000;36:2185– 91. 31. Barenbrock M, Hausberg M, Kosch M, Golubev SA, Kisters K, Rahn KH. Flow-mediated vasodilation and distensibility in relation to intima-media thickness of large arteries in mild essential hypertension. Am J Hypertens 1999;12:973–9. 32. Hashimoto M, Eto M, Akishita M, et al. Correlation between flow-mediated vasodilatation of the brachial artery and intima-media thickness in the carotid artery in men. Arterioscler Thromb Vasc Biol 1999; 19:2795–800. 33. van Guldener C, Janssen MJ, Lambert J, et al. No change in impaired endothelial function after long-term folic acid therapy of hyperhomocysteinaemia in haemodialysis patients. Nephrol Dial Transplant 1998;13:106–12. 34. Simons LA, von Konigsmark M, Simons J, Celermajer DS. Phytoestrogens do not influence lipoprotein levels or endothelial function in healthy, postmenopausal women. Am J Cardiol 2000;85:1297–301. 35. Hijmering ML, Stroes ES, Pasterkamp G, Sierevogel M, Banga JD, Rabelink TJ. Variability of flow-mediated dilation: consequences for clinical application. Atherosclerosis 2001;157:369–73. 36. Alonso R, Mata P, De Andres R, Villacastin BP, Martinez-Gonzalez J, Badimon L. Sustained long-term improvement of arterial endothelial function in heterozygous familial hypercholesterolemia patients treated with simvastatin. Atherosclerosis 2001;157:423–9. 37. de Roos NM, Bots ML, Katan MB. 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 2001;21:1233–7. 38. Enderle MD, Schroeder S, Ossen R, et al. Comparison of peripheral endothelial dysfunction and intimal media thickness in patients with suspected coronary artery disease. Heart 1998;80:349–54. 39. Jodoin I, Bussieres LM, Tardif JC, Juneau M. Effect of a short-term primary prevention program on endothelium-dependent vasodilation in adults at risk for atherosclerosis. Can J Cardiol 1999;15:83–8. 40. Anderson TJ, Uehata A, Gerhard MD, et al. Close relation of endothelial function in the human coronary and peripheral circulations. J Am Coll Cardiol 1995;26:1235–41. 41. de Kleijn MJ, Wilmink HW, Bots ML, et al. Hormone replacement therapy and endothelial function. Results of a randomized controlled trial in healthy postmenopausal women. Atherosclerosis 2001; 159:357–65. 42. Spieker LE, Sudano I, Hurlimann D, et al. High–density lipoprotein restores endothelial function in hypercholesterolemic men. Circulation 2002;105:1399–402. 43. Diercks GF, Stroes ES, van Boven AJ, et al. Urinary albumin excretion is related to cardiovascular risk indicators, not to flow-mediated vasodilation, in apparently healthy subjects. Atherosclerosis 2002;163:121–6. 44. de Jongh S, Lilien MR, Bakker HD, Hutten BA, Kastelein JJ, Stroes ES. Family history of cardiovascular events and endothelial dysfunction in children with familial hypercholesterolemia. Atherosclerosis 2002;163:193–7. 45. Clarkson P, Celermajer DS, Powe AJ, Donald AE, Henry RM, Deanfield JE. Endothelium-dependent dilatation is impaired in young healthy subjects with a family history of premature coronary disease. Circulation 1997;96:3378–83. 46. Furumoto T, Fujii S, Saito N, Mikami T, Kitabatake A. Relationships between brachial artery flow mediated dilation and carotid artery intima-media thickness in patients with suspected coronary artery disease. Jpn Heart J 2002;43:117–25. 47. van Venrooij FV, van de Ree MA, Bots ML, Stolk RP, Huisman MV, Banga JD. Aggressive lipid lowering does not improve endothelial function in type 2 diabetes: the Diabetes Atorvastatin Lipid Intervention (DALI) Study: a randomized, double-blind, placebo-controlled trial. Diabetes Care 2002;25:1211–6. 48. Yataco AR, Corretti MC, Gardner AW, Womack CJ, Katzel LI. Endothelial reactivity and cardiac risk factors in older patients with peripheral arterial disease. Am J Cardiol 1999;83:754–8. 49. Lambert J, van den BM, Steyn M, Rauwerda JA, Donker AJ, Stehouwer CD. Familial hyperhomocysteinaemia and endothelium-dependent vasodilatation and arterial distensibility of large arteries. Cardiovasc Res 1999;42:743–51. 50. Jarvisalo MJ, Ronnemaa T, Volanen I, et al. Brachial artery dilatation responses in healthy children and adolescents. Am J Physiol Heart Circ Physiol 2002;282:H87–92. 51. Kosch M, Hausberg M, Vormbrock K, Kisters K, Rahn KH, Barenbrock M. Studies on flow-mediated vasodilation and intima-media thickness of the brachial artery in patients with primary hyperparathyroidism. Am J Hypertens 2000;13:759– 64. 52. Jensen-Urstad K, Johansson J. Gender difference in age-related changes in vascular function. J Intern Med 2001;250:29–36. 53. Aggoun Y, Bonnet D, Sidi D, et al. Arterial mechanical changes in children with familial hypercholesterolemia. Arterioscler Thromb Vasc Biol 2000;20:2070–5. 54. Jarvisalo MJ, Harmoinen A, Hakanen M, et al. Elevated serum C-reactive protein levels and early arterial changes in healthy children. Arterioscler Thromb Vasc Biol 2002;22:1323–8. 55. Teragawa H, Fukuda Y, Matsuda K, et al. Effect of alcohol consumption on endothelial function in men with coronary artery disease. Atherosclerosis 2002;165:145–52. 56. Monnink SH, van Haelst PL, van Boven AJ, et al. Endothelial dysfunction in patients with coronary artery disease: a comparison of three frequently reported tests. J Investig Med 2002;50:19–24. 57. Ravikumar R, Deepa R, Shanthirani C, Mohan V. Comparison of carotid intima–media thickness, arterial stiffness, and brachial artery flow mediated dilatation in diabetic and nondiabetic subjects (The Chennai Urban Population Study [CUPS9]). Am J Cardiol 2002;90:702–7. 58. Weidinger F, Frick M, Alber HF, Ulmer H, Schwarzacher SP, Pachinger O. Association of wall thickness of the brachial artery measured with high-resolution ultrasound with risk factors and coronary artery disease. Am J Cardiol 2002;89:1025– 9. 59. Dalli E, Segarra L, Ruvira J, et al. [Brachial artery flow-mediated dilation in healthy men, men with risk factors, and men with acute myocardial infarction. Importance of occlusion-cuff position]. Rev Esp Cardiol 2002;55:928–35. 60. Andrews TC, Whitney EJ, Green G, Kalenian R, Personius BE. Effect of gemfibrozil +/– niacin +/– cholestyramine on endothelial function in patients with serum low–density lipoprotein cholesterol levels <160 mg/dl and high-density lipoprotein cholesterol levels <40 mg/dl. Am J Cardiol 1997;80:831–5. 61. Barua RS, Ambrose JA, Eales-Reynolds LJ, DeVoe MC, Zervas JG, Saha DC. Dysfunctional endothelial nitric oxide biosynthesis in healthy smokers with impaired endothelium-dependent vasodilatation. Circulation 2001;104:1905–10. 62. Botker HE, Sonne HS, Sorensen KE. Frequency of systemic microvascular dysfunction in syndrome X and in variant angina. Am J Cardiol 1996;78:182–6. 63. Park JB, Charbonneau F, Schiffrin EL. Correlation of endothelial function in large and small arteries in human essential hypertension. J Hypertens. 2001;19:415– 20. 64. Ghiadoni L, Donald AE, Cropley M, et al. Mental stress induces transient endothelial dysfunction in humans. Circulation 2000;102:2473–8. 65. Evans LM, Davies JS, Goodfellow J, Rees JA, Scanlon MF. Endothelial dysfunction in hypopituitary adults with growth hormone deficiency. Clin Endocrinol (Oxf) 1999;50:457–64. 66. Dhillon R, Clarkson P, Donald AE, et al. Endothelial dysfunction late after Kawasaki disease. Circulation 1996;94:2103–6. 67. Wilmink HW, Twickler MB, Banga JD, et al. Effect of statin versus fibrate on postprandial endothelial dysfunction: role of remnant-like particles. Cardiovasc Res 2001;50:577–82. 68. Wilson DG, Bellamy MF, Ramsey MW, et al. Endothelial function in Marfan syndrome: selective impairment of flow-mediated vasodilation. Circulation 1999;99:909–15. 69. Woo KS, Chook P, Lolin YI, Sanderson JE, Metreweli C, Celermajer DS. Folic acid improves arterial endothelial function in adults with hyperhomocystinemia. J Am Coll Cardiol 1999;34:2002–6. 70. Stein JH, Carlsson CM, Papcke-Benson K, et al. The effects of lipid-lowering and antioxidant vitamin therapies on flow-mediated vasodilation of the brachial artery in older adults with hypercholesterolemia. J Am Coll Cardiol 2001;38:1806–13. 71. Tawakol A, Omland T, Gerhard M, Wu JT, Creager MA. Hyperhomocyst(e)inemia is associated with impaired endothelium-dependent vasodilation in humans. Circulation 1997;95:1119–21. 72. Woo KS, Chook P, Lolin YI, et al. Hyperhomocyst(e)inemia is a risk factor for arterial endothelial dysfunction in humans. Circulation 1997;96:2542–4. 73. Usui M, Matsuoka H, Miyazaki H, Ueda S, Okuda S, Imaizumi T. Endothelial dysfunction by acute hyperhomocyst(e)inaemia: restoration by folic acid. Clin Sci (Lond) 1999;96:235–9. 74. Stein JH, Klein MA, Bellehumeur JL, et al. Use of human immunodeficiency virus–1 protease inhibitors is associated with atherogenic lipoprotein changes and endothelial dysfunction. Circulation 2001;104:257–62. 75. Watts GF, Herrmann S, Dogra GK, et al. Vascular function of the peripheral circulation in patients with nephrosis. Kidney Int. 2001;60:182–9. 76. Williams MJ, Sutherland WH, McCormick MP, de Jong SA, Walker RJ, Wilkins GT. Impaired endothelial function following a meal rich in used cooking fat. J Am Coll Cardiol 1999;33:1050–5. 77. Kawano H, Motoyama T, Hirai N, et al. Effect of medroxyprogesterone acetate plus estradiol on endothelium-dependent vasodilation in postmenopausal women. Am J Cardiol 2001;87:238–40. 78. Schalkwijk CG, Smulders RA, Lambert J, Donker AJ, Stehouwer CD. ACE- inhibition modulates some endothelial functions in healthy subjects and in normotensive type 1 diabetic patients. Eur J Clin Invest 2000;30:853–60. 79. Williams MJ, Sutherland WH, McCormick MP, de Jong SA, McDonald JR, Walker RJ. Vitamin C improves endothelial dysfunction in renal allograft recipients. Nephrol Dial Transplant 2001;16:1251–5. 80. Worboys S, Kotsopoulos D, Teede H, McGrath B, Davis SR. Evidence that parenteral testosterone therapy may improve endothelium-dependent and - independent vasodilation in postmenopausal women already receiving estrogen. J Clin Endocrinol Met 2001;86:158–61. 81. The CAG repeat polymorphism in the AR gene affects high density lipoprotein cholesterol and arterial vasoreactivity. J Clin Endocrinol Met 2001;86:4867–73. 82. Nightingale AK, Blackman DJ, Ellis GR, et al. Preservation of venous endothelial function in the forearm venous capacitance bed of patients with chronic heart failure despite arterial endothelial dysfunction. J Am Coll Cardiol 2001;37:1062–8. 83. Brook RD, Bard RL, Rubenfire M, Ridker PM, Rajagopalan S. Usefulness of visceral obesity (waist/hip ratio) in predicting vascular endothelial function in healthy overweight adults. Am J Cardiol 2001;88:1264–9. 84. Cagnacci A, Modena MG, Malmusi S, Muia N, Volpe A. Effect of prolonged administration of transdermal estradiol on flow-mediated endothelium-dependent and endothelium-independent vasodilation in healthy postmenopausal women. Am J Cardiol 1999;84:367–10. 85. Chambers JC, Obeid OA, Kooner JS. Physiological increments in plasma homocysteine induce vascular endothelial dysfunction in normal human subjects. Arterioscler Thromb Vasc Biol 1999;19:2922–7. 86. Chambers JC, Haskard DO, Kooner JS. Vascular endothelial function and oxidative stress mechanisms in patients with Behcet’s syndrome. J Am Coll Cardiol 2001;37:517–20. 87. Chao CL, Kuo TL, Lee YT. Effects of methionine-induced hyperhomocysteinemia on endothelium-dependent vasodilation and oxidative status in healthy adults. Circulation 2000;101:485–90. 88. Cheetham C, O’Driscoll G, Stanton K, Taylor R, Green D. Losartan, an angiotensin type I receptor antagonist, improves conduit vessel endothelial function in type II diabetes. Clin Sci (Lond) 2001;100:13–7. 89. Clarke SC, Schofield PM, Grace AA, Metcalfe JC, Kirschenlohr HL. Tamoxifen effects on endothelial function and cardiovascular risk factors in men with advanced atherosclerosis. Circulation 2001;103:1497–502. 90. Clarkson P, Celermajer DS, Donald AE, et al. Impaired vascular reactivity in insulin-dependent diabetes mellitus is related to disease duration and low density lipoprotein cholesterol levels. J Am Coll Cardiol 1996;28:573–9. 91. Corretti MC, Plotnick GD, Vogel RA. Correlation of cold pressor and flow- mediated brachial artery diameter responses with the presence of coronary artery disease. Am J Cardiol 1995;75:783–7. 92. Corretti MC, Plotnick GD, Vogel RA. Smoking correlates with flow–mediated brachial artery vasoactivity but not cold pressor vasoactivity in men with coronary artery disease. Int J Card Imaging 1998;14:11–7. 93. Li J, Zhao SP, Li XP, Zhuo QC, Gao M, Lu SK. Non-invasive detection of endothelial dysfunction in patients with essential hypertension. Int J Cardiol 1997;61:165–9. 94. Li XP, Zhao SP, Zhang XY, Liu L, Gao M, Zhou QC. Protective effect of high density lipoprotein on endothelium-dependent vasodilatation. Int J Cardiol 2000;73:231–6. 95. Lekakis J, Papamichael C, Anastasiou H, et al. Endothelial dysfunction of conduit arteries in insulin-dependent diabetes mellitus without microalbuminuria. Cardiovasc Res 1997;34 :164–8. 96. Lin CL, Fang TC, Gueng MK. Vascular dilatory functions of ovo- lactovegetarians compared with omnivores. Atherosclerosis 2001;158:247–51. 97. Mullen MJ, Clarkson P, Donald AE, et al. Effect of enalapril on endothelial function in young insulin-dependent diabetic patients: a randomized, double-blind study. J Am Coll Cardiol 1998;31:1330–5. 98. Mullen MJ, Wright D, Donald AE, Thorne S, Thomson H, Deanfield JE. Atorvastatin but not L-arginine improves endothelial function in type I diabetes mellitus: a double-blind study. J Am Coll Cardiol 2000;36:410–6. 99. Meco JF, Vila R, Pujol R, et al. Improvement in endothelial dysfunction in patients with hypoalphalipoproteinemia and coronary artery disease treated with bezafibrate. J Cardiovasc Pharmacol 2001;38:250–8. 100. Maiorana A, O'Driscoll G, Cheetham C, Dembo L, Stanton K, Goodman C et al. The effect of combined aerobic and resistance exercise training on vascular function in type 2 diabetes. J Am Coll Cardiol 2001;38:860–6. 101. Maiorano G, Bartolomucci F, Contursi V, et al. Noninvasive detection of vascular dysfunction in alcoholic patients. Am J Hypertens 1999;12:137–44. 102. Dogra G, Rich L, Stanton K, Watts GF. Endothelium-dependent and independent vasodilation studies at normoglycaemia in type I diabetes mellitus with and without microalbuminuria. Diabetologia 2001;44:593–601. 103. Doshi SN, Naka KK, Payne N, et al. Flow-mediated dilatation following wrist and upper arm occlusion in humans: the contribution of nitric oxide. Clin.Sci.(Lond) 2001;101:629–35. 104. Duffy SJ, Keaney JF, Jr., Holbrook M, et al. Short- and long-term black tea consumption reverses endothelial dysfunction in patients with coronary artery disease. Circulation 2001;104:151–6. 105. Ebenbichler CF, Sturm W, Ganzer H, et al. Flow-mediated, endothelium- dependent vasodilatation is impaired in male body builders taking anabolicandrogenic steroids. Atherosclerosis 2001;158:483–90. 106. Guzic-Salobir B, Keber I, Seljeflot I, Arnesen H, Vrabic L. Combined hormone replacement therapy improves endothelial function in healthy postmenopausal women. J Intern Med 2001;250:508–15. 107. Gokce N, Holbrook M, Duffy SJ, et al. Effects of race and hypertension on flow-mediated and nitroglycerin-mediated dilation of the brachial artery. Hypertension 2001;38:1349–54. 108. Gaenzer H, Neumayr G, Marschang P, Sturm W, Kirchmair R, Patsch JR. Flow-mediated vasodilation of the femoral and brachial artery induced by exercise in healthy nonsmoking and smoking men. J Am Coll Cardiol 2001;38:1313–9. 109. Hausberg M, Kosch M, Stam F, et al. Effect of fluvastatin on endothelium- dependent brachial artery vasodilation in patients after renal transplantation. Kidney Int. 2001;59:1473–9. 110. Kawano H, Motoyama T, Kugiyama K, et al. Gender difference in improvement of endothelium-dependent vasodilation after estrogen supplementation. J Am Coll Cardiol 1997;30:914–9. 111. New G, Timmins KL, Duffy SJ, et al. Long-term estrogen therapy improves vascular function in male to female transsexuals. J Am Coll Cardiol 1997;29:1437– 44. 112. Neunteufl T, Priglinger U, Heher S, et al. Effects of vitamin E on chronic and acute endothelial dysfunction in smokers. J Am Coll Cardiol 2000;35:277–83. 113. Hirai N, Kawano H, Hirashima O, et al. Insulin resistance and endothelial dysfunction in smokers: effects of vitamin C. Am J Physiol Heart Circ Physiol 2000;279:H1172–8. 114. Savvidou MD, Vallance PJ, Nicolaides KH, Hingorani AD. Endothelial nitric oxide synthase gene polymorphism and maternal vascular adaptation to pregnancy. Hypertension 2001;38:1289–93. 115. Prasad A, Tupas-Habib T, Schenke WH, et al. Acute and chronic angiotensin- 1 receptor antagonism reverses endothelial dysfunction in atherosclerosis. Circulation 2000;101:2349–54. 116. McCredie RJ, McCrohon JA, Turner L, Griffiths KA, Handelsman DJ, Celermajer DS. Vascular reactivity is impaired in genetic females taking high-dose androgens. J Am Coll Cardiol 1998;32:1331–5. 117. Saitta A, Altavilla D, Cucinotta D, et al. Randomized, double-blind, placebo- controlled study on effects of raloxifene and hormone replacement therapy on plasma no concentrations, endothelin-1 levels, and endothelium-dependent vasodilation in postmenopausal women. Arterioscler Thromb Vasc Biol 2001;21:1512–9. 118. Koh KK, Jin DK, Yang SH, et al. Vascular effects of synthetic or natural progestagen combined with conjugated equine estrogen in healthy postmenopausal women. Circulation 2001;103:1961–6. 119. Kaku B, Mizuno S, Ohsato K, et al. The correlation between coronary stenosis index and flow-mediated dilation of the brachial artery. Jpn Circ J 1998;62:425–30. 120. Kawano H, Motoyama T, Hirai N, Kugiyama K, Ogawa H, Yasue H. Estradiol supplementation suppresses hyperventilation-induced attacks in postmenopausal women with variant angina. J Am Coll Cardiol 2001;37:735–40. 121. Wakatsuki A, medroxyprogesterone Okatani acetate Y, on Ikenoue N, Fukaya endothelium-dependent T. Effect of vasodilation in postmenopausal women receiving estrogen. Circulation 2001;104:1773–8. 122. Lavrencic A, Salobir BG, Keber I. Physical training improves flow-mediated dilation in patients with the polymetabolic syndrome. Arterioscler Thromb Vasc Biol 2000;20:551–5. 123. Lee SJ, Lee DW, Kim KS, Lee IK. Effect of estrogen on endothelial dysfunction in postmenopausal women with diabetes. Diabetes Res Clin Pract 2001;54 Suppl 2:S81–92. 124. Imamura M, Biro S, Kihara T, et al. Repeated thermal therapy improves impaired vascular endothelial function in patients with coronary risk factors. J Am Coll Cardiol 2001;38:1083–8. 125. Johansson J, Jensen-Urstad K, Jensen-Urstad M. Antiplasmin correlates to arterial reactivity in a healthy population of 35-year-old men and women. J Intern Med 1999;245:21–9. 126. Neunteufl T, Heher S, Kostner K, et al. Contribution of nicotine to acute endothelial dysfunction in long-term smokers. J Am Coll Cardiol 2002;39:251–6. 127. Adams MR, McCredie R, Jessup W, Robinson J, Sullivan D, Celermajer DS. Oral L-arginine improves endothelium-dependent dilatation and reduces monocyte adhesion to endothelial cells in young men with coronary artery disease. Atherosclerosis 1997;129:261–9. 128. Adams MR, Forsyth CJ, Jessup W, Robinson J, Celermajer DS. Oral L- arginine inhibits platelet aggregation but does not enhance endothelium-dependent dilation in healthy young men. J Am Coll Cardiol 1995;26:1054–61. 129. Allen JD, Wilson JB, Tulley RT, Lefevre M, Welsch MA. Influence of age and normal plasma fibrinogen levels on flow-mediated dilation in healthy adults. Am J Cardiol 2000;86:703–5. 130. Balletshofer BM, Rittig K, Enderle MD, et al. Endothelial dysfunction is detectable in young normotensive first-degree relatives of subjects with type 2 diabetes in association with insulin resistance. Circulation 2000;101:1780–4. 131. Brook RD, Brook JR, Urch B, Vincent R, Rajagopalan S, Silverman F. Inhalation of fine particulate air pollution and ozone causes acute arterial vasoconstriction in healthy adults. Circulation 2002;105:1534–6. 132. Campia U, Choucair WK, Bryant MB, Waclawiw MA, Cardillo C, Panza JA. Reduced endothelium-dependent and -independent dilation of conductance arteries in African Americans. J Am Coll Cardiol 2002;40:754–60. 133. Clarkson P, Mullen MJ, Donald AE, et al. The effect of amlodipine on endothelial function in young adults with a strong family history of premature coronary artery disease: a randomised double blind study. Atherosclerosis 2001;154:171–7. 134. Clarkson P, Adams MR, Powe AJ, et al. Oral L–arginine improves endothelium-dependent dilation in hypercholesterolemic young adults. J Clin Invest 1996;97:1989–94. 135. Clausen P, Jensen JS, Jensen G, Borch-Johnsen K, Feldt-Rasmussen B. Elevated urinary albumin excretion is associated with impaired arterial dilatory capacity in clinically healthy subjects. Circulation 2001;103:1869–74. 136. Djousse L, Ellison RC, McLennan CE, et al. Acute effects of a high-fat meal with and without red wine on endothelial function in healthy subjects. Am J Cardiol 1999;84:660–4. 137. Dogra G, Watts GF. Endothelial dysfunction in type 1 diabetes mellitus: methodological considerations. Diabet Med 2000;17:687–8. 138. Doshi SN, McDowell IF, Moat SJ, et al. Folate improves endothelial function in coronary artery disease: an effect mediated by reduction of intracellular superoxide? Arterioscler Thromb Vasc Biol 2001;21:1196–202. 139. Evans LM, Davies JS, Anderson RA, et al. The effect of GH replacement therapy on endothelial function and oxidative stress in adult growth hormone deficiency. Eur J Endocrinol 2000;142:254–62. 140. Evans M, Anderson RA, Graham J, et al. Ciprofibrate therapy improves endothelial function and reduces postprandial lipemia and oxidative stress in type 2 diabetes mellitus. Circulation 2000;101:1773–9. 141. Fard A, Tuck CH, Donis JA, et al. Acute elevations of plasma asymmetric dimethylarginine and impaired endothelial function in response to a high-fat meal in patients with type 2 diabetes. Arterioscler Thromb Vasc Biol 2000;20:2039–44. 142. Funada J, Sekiya M, Hamada M, Hiwada K. Postprandial elevation of remnant lipoprotein leads to endothelial dysfunction. Circ J 2002;66:127–32. 143. Gaenzer H, Neumayr G, Marschang P, et al. Effect of insulin therapy on endothelium-dependent dilation in type 2 diabetes mellitus. Am J Cardiol 2002;89:431–4. 144. Gaenzer H, Sturm W, Neumayr G, et al. Pronounced postprandial lipemia impairs endothelium-dependent dilation of the brachial artery in men. Cardiovasc Res 2001;52:509–16. 145. Gokce N, Keaney JF, Jr., Frei B, et al. Long-term ascorbic acid administration reverses endothelial vasomotor dysfunction in patients with coronary artery disease. Circulation 1999;99:3234–40. 146. Greiner DZ, Personius BE, Andrews TC. Effects of withdrawal of chronic estrogen therapy on brachial artery vasoreactivity in women with coronary artery disease. Am J Cardiol 1999;83:247–9. 147. Herman SM, Robinson JT, McCredie RJ, Adams MR, Boyer MJ, Celermajer DS. Androgen deprivation is associated with enhanced endothelium–dependent dilatation in adult men. Arterioscler Thromb Vasc Biol 1997;17:2004–9. 148. Hijmering ML, Stroes ES, Olijhoek J, Hutten BA, Blankestijn PJ, Rabelink TJ. Sympathetic activation markedly reduces endothelium-dependent, flow-mediated vasodilation. J Am Coll Cardiol 2002;39:683–8. 149. Hirashima O, Kawano H, Motoyama T, et al. Improvement of endothelial function and insulin sensitivity with vitamin C in patients with coronary spastic angina: possible role of reactive oxygen species. J Am Coll Cardiol 2000;35:1860–6. 150. Hoffmann U, Dirisamer A, Heher S, Kostner K, Widhalm K, Neunteufl T. Relation of peripheral flow-mediated vasodilatation and coronary arterial calcium in young patients with heterozygous familial hypercholesterolemia. Am J Cardiol 2002;90:70–3. 151. Hurlimann D, Forster A, Noll G, et al. Anti-tumor necrosis factor-alpha treatment improves endothelial function in patients with rheumatoid arthritis. Circulation 2002;106:2184–7. 152. Irace C, Ceravolo R, Notarangelo L, et al. Comparison of endothelial function evaluated by strain gauge plethysmography and brachial artery ultrasound. Atherosclerosis 2001;158:53–9. 153. Jartti L, Ronnemaa T, Kaprio J, et al. Population-based twin study of the effects of migration from Finland to Sweden on endothelial function and intimamedia thickness. Arterioscler Thromb Vasc Biol 2002;22:832–7. 154. Koh KK, Son JW, Ahn JY, et al. Comparative effects of diet and statin on NO bioactivity and matrix metalloproteinases in hypercholesterolemic patients with coronary artery disease. Arterioscler Thromb Vasc Biol 2002;22:e19–e23. 155. Koh KK, Son JW, Ahn JY, et al. Effect of hormone replacement therapy on nitric oxide bioactivity and monocyte chemoattractant protein-1 levels. Int J Cardiol 2001;81:43–50. 156. Komatsu M, Kawagishi T, Emoto M, et al. ecNOS gene polymorphism is associated with endothelium-dependent vasodilation in type 2 diabetes. Am J Physiol Heart Circ Physiol 2002;283:H557–61. 157. Kugiyama K, Motoyama T, Doi H, et al. Improvement of endothelial vasomotor dysfunction by treatment with alpha-tocopherol in patients with high remnant lipoproteins levels. J Am Coll Cardiol 1999;33:1512–8. 158. Lupattelli G, Marchesi S, Roscini AR, et al. Direct association between high- density lipoprotein cholesterol and endothelial function in hyperlipemia. Am J Cardiol 2002;90:648–50. 159. Ma LN, Zhao SP, Gao M, Zhou QC, Fan P. Endothelial dysfunction associated with left ventricular diastolic dysfunction in patients with coronary heart disease. Int J Cardiol 2000;72:275–9. 160. Malik J, Melenovsky V, Wichterle D, Haas T, Simek J, Ceska R et al. Both fenofibrate and atorvastatin improve vascular reactivity in combined hyperlipidaemia (fenofibrate versus atorvastatin trial––FAT). Cardiovasc Res 2001;52:290–8. 161. Mather KJ, Verma S, Corenblum B, Anderson TJ. Normal endothelial function despite insulin resistance in healthy women with the polycystic ovary syndrome. J Clin Endocrinol Metab 2000;85:1851–6. 162. McCrohon JA, Woo KS, Celermajer DS. A comparison of endothelial function in Caucasian and Chinese women before and after the menopause. Maturitas 2000;35:31–7. 163. McCrohon JA, Walters WA, Robinson JT, et al. Arterial reactivity is enhanced in genetic males taking high dose estrogens. J Am Coll Cardiol 1997;29:1432–6. 164. Motoyama T, Kawano H, Kugiyama K, et al. Endothelium-dependent vasodilation in the brachial artery is impaired in smokers: effect of vitamin C. Am J Physiol 1997;273:H1644–50. 165. Nightingale AK, James PP, Morris-Thurgood J, et al. Evidence against oxidative stress as mechanism of endothelial dysfunction in methionine loading model. Am J Physiol Heart Circ Physiol 2001;280:H1334–9. 166. Paolisso G, Manzella D, Tagliamonte MR, et al. The BB–paraoxonase genotype is associated with impaired brachial reactivity after acute hypertriglyceridemia in healthy subjects. J Clin Endocrinol Metab 2001;86:1078–82. 167. Parchure N, Zouridakis EG, Kaski JC. Effect of azithromycin treatment on endothelial function in patients with coronary artery disease and evidence of Chlamydia pneumoniae infection. Circulation 2002;105:1298–303. 168. Pfeifer M, Verhovec R, Zizek B, Prezelj J, Poredos P, Clayton RN. Growth hormone (GH) treatment reverses early atherosclerotic changes in GH-deficient adults. J Clin Endocrinol Metab 1999;84:453–7. 169. Raitakari OT, McCredie RJ, Witting P, et al. Coenzyme Q improves LDL resistance to ex vivo oxidation but does not enhance endothelial function in hypercholesterolemic young adults. Free Radic Biol Med 2000;28:1100–5. 170. Rajagopalan S, Brook R, Mehta RH, Supiano M, Pitt B. Effect of losartan in aging-related endothelial impairment. Am J Cardiol 2002;89:562–6. 171. Rinder MR, Spina RJ, Ehsani AA. Enhanced endothelium-dependent vasodilation in older endurance-trained men. J Appl Physiol 2000;88:761–6. 172. Rywik TM, Blackman MR, Yataco AR, et al. Enhanced endothelial vasoreactivity in endurance-trained older men. J Appl Physiol 1999;87:2136–42. 173. Sorensen MB, Collins P, Ong PJ, et al. Long–term use of contraceptive depot medroxyprogesterone acetate in young women impairs arterial endothelial function assessed by cardiovascular magnetic resonance. Circulation 2002;106:1646–51. 174. Tan KC, Ai VH, Chow WS, Chau MT, Leong L, Lam KS. Influence of low density lipoprotein (LDL) subfraction profile and LDL oxidation on endotheliumdependent and independent vasodilation in patients with type 2 diabetes. J Clin Endocrinol Metab 1999;84:3212–6. 175. Thambyrajah J, Landray MJ, McGlynn FJ, Jones HJ, Wheeler DC, Townend JN. Does folic acid decrease plasma homocysteine and improve endothelial function in patients with predialysis renal failure? Circulation 2000;102:871–5. 176. Thorne S, Mullen MJ, Clarkson P, Donald AE, Deanfield JE. Early endothelial dysfunction in adults at risk from atherosclerosis: different responses to L-arginine. J Am Coll Cardiol 1998;32:110–6. 177. Toikka JO, Laine H, Ahotupa M, et al. Increased arterial intima-media thickness and in vivo LDL oxidation in young men with borderline hypertension. Hypertension 2000;36:929–33. 178. Tomiyama H, Kimura Y, Okazaki R, et al. Close relationship of abnormal glucose tolerance with endothelial dysfunction in hypertension. Hypertension 2000;36:245–9. 179. van Dijk RA, Rauwerda JA, Steyn M, Twisk JW, Stehouwer CD. Long–term homocysteine-lowering treatment with folic acid plus pyridoxine is associated with decreased blood pressure but not with improved brachial artery endotheliumdependent vasodilation or carotid artery stiffness: a 2-year, randomized, placebocontrolled trial. Arterioscler Thromb Vasc Biol 2001;21:2072–9. 180. Vita JA, Frei B, Holbrook M, Gokce N, Leaf C, Keaney JF, Jr. L-2- Oxothiazolidine-4-carboxylic acid reverses endothelial dysfunction in patients with coronary artery disease. J Clin Invest 1998;101:1408–14. 181. Vogel RA, Corretti MC, Plotnick GD. Effect of a single high-fat meal on endothelial function in healthy subjects. Am J Cardiol 1997;79:350–4. 182. Watts GF, Playford DA, Croft KD, Ward NC, Mori TA, Burke V. Coenzyme Q(10) improves endothelial dysfunction of the brachial artery in type II diabetes mellitus. Diabetologia 2002;45:420–6. 183. Woo KS, Chook P, Chan LL, et al. Long-term improvement in homocysteine levels and arterial endothelial function after 1-year folic acid supplementation. Am J Med 2002;112:535–9. 184. Woodman RJ, Watts GF, Puddey IB, et al. Leukocyte count and vascular function in type 2 diabetic subjects with treated hypertension. Atherosclerosis 2002;163:175–81. 185. Smith JC, Evans LM, Wilkinson I, et al. Effects of GH replacement on endothelial function and large-artery stiffness in GH-deficient adults: a randomized, double-blind, placebo-controlled study. Clin Endocrinol (Oxf) 2002;56:493–501. 186. Hale G, Paul-Labrador M, Dwyer JH, Merz CN. Isoflavone supplementation and endothelial function in menopausal women. Clin Endocrinol (Oxf) 2002;56:693– 701. 187. Woo KS, McCrohon JA, Chook P, et al. Chinese adults are less susceptible than whites to age-related endothelial dysfunction. J Am Coll Cardiol 1997;30:113–8. 188. Hershkovitz E, Donald A, Mullen M, Lee PJ, Leonard JV. Blood lipids and endothelial function in glycogen storage disease type III. J Inherit Metab Dis 1999;22:891–8. 189. Marchesi S, Lupattelli G, Siepi D, et al. Oral L-arginine administration attenuates postprandial endothelial dysfunction in young healthy males. J Clin Pharm Ther 2001;26:343–9. 190. Lupattelli G, Lombardini R, Schillaci G, et al. Flow-mediated vasoactivity and circulating adhesion molecules in hypertriglyceridemia: association with small, dense LDL cholesterol particles. Am Heart J 2000;140:521–6. 191. Matsuda Y, Akita H, Terashima M, Shiga N, Kanazawa K, Yokoyama M. Carvedilol improves endothelium-dependent dilatation in patients with coronary artery disease. Am Heart J 2000;140:753–9. 192. Title LM, Cummings PM, Giddens K, Genest JJ, Jr., Nassar BA. Effect of folic acid and antioxidant vitamins on endothelial dysfunction in patients with coronary artery disease. J Am Coll Cardiol 2000;36:758–65. 193. Celermajer DS, Sorensen KE, Barley J, Jeffrey S, Carter N, Deanfield J. Angiotensin–converting enzyme genotype is not associated with endothelial dysfunction in subjects without other coronary risk factors. Atherosclerosis 1994;111:121–6. 194. Chambers JC, Fusi L, Malik IS, Haskard DO, De Swiet M, Kooner JS. Association of maternal endothelial dysfunction with preeclampsia. JAMA 2001;285:1607–12. 195. Corretti MC, Plotnick GD, Vogel RA. The effects of age and gender on brachial artery endothelium–dependent vasoactivity are stimulus-dependent. Clin Cardiol 1995;18:471–6. 196. Hashimoto M, Akishita M, Eto M, et al. The impairment of flow-mediated vasodilatation in obese men with visceral fat accumulation. Int J Obes Relat Metab Disord 1998;22:477–84. 197. Jensen-Urstad K, Johansson J, Jensen-Urstad M. Vascular function correlates with risk factors for cardiovascular disease in a healthy population of 35-year-old subjects. J Intern Med 1997;241:507–13. 198. Kimura Y, Matsumoto M, Miyauchi E, Deng YB, Iwai K, Hattori H. Noninvasive detection of endothelial dysfunction in elderly with NIDDM by ultrasonography. Echocardiography 2001;18:559–64. 199. Motoyama T, Kawano H, Hirai N, et al. The relationship of left ventricular mass to endothelium-dependent vasodilation of the brachial artery in patients with hypertension. Cardiology 2001;96:7–15. 200. Ng CK, Chan AP, Cheng A. Impairment of endothelial function––a possible mechanism for atherosclerosis of a high-fat meal intake. Ann Acad Med Singapore 2001;30:499–502. 201. Ringqvist A, Jonason T, Leppert J, Ringqvist I. Non-invasive investigation of endothelium-dependent dilatation of the brachial artery in women with primary Raynaud’s phenomenon. Clin Sci (Lond) 1998;94:239–43. 202. Uehata A, Lieberman EH, Gerhard MD, et al. Noninvasive assessment of endothelium-dependent flow-mediated dilation of the brachial artery. Vasc Med 1997;2:87–92. 203. Yildirir A, Tokgozoglu SL, Oduncu T, et al. Soy protein diet significantly improves endothelial function and lipid parameters. Clin Cardiol 2001;24:711–6. 204. Zhao SP, Liu L, Gao M, Zhou QC, Li YL, Xia B. Impairment of endothelial function after a high-fat meal in patients with coronary artery disease. Coron Artery Dis 2001;12:561–5.