(Circulation. 2001;103:919.)
© 2001 American Heart Association, Inc.
Clinical Investigation and Reports |
Effects of Ramipril and Vitamin E on Atherosclerosis
The Study to Evaluate Carotid Ultrasound Changes in Patients Treated With Ramipril and Vitamin E (SECURE)
From the Departments of Medicine (E.M.L., S.Y., Q.Y., S.S., A.M.-C., J.B., K.K.T.) and Radiology (C.I.D.), McMaster University, Hamilton, Ontario, Canada; The University of Alberta Hospitals, Edmonton, Alberta, Canada (V.D., K.K.T.); the Canadian Cardiovascular Collaboration (E.M.L., S.Y., V.D., C.I.D., Q.Y., S.S., A.M.-C., J.B., K.K.T.); and the Bowman Gray School of Medicine, Department of Neurology, Winston-Salem, NC (W.A.R.).
Correspondence to Eva Lonn, MD, Hamilton Health Sciences Corporation, General Site, 237 Barton Street East, Hamilton, Ontario, Canada L8L 2X2. E-mail hope{at}ccc.mcmaster.ca
Background—Activation of the renin-angiotensin-aldosterone system and oxidative modification of LDL cholesterol play important roles in atherosclerosis. The Study to Evaluate Carotid Ultrasound changes in patients treated with Ramipril and vitamin E (SECURE), a substudy of the Heart Outcomes Prevention Evaluation (HOPE) trial, was a prospective, double-blind, 3x2 factorial design trial that evaluated the effects of long-term treatment with the angiotensin-converting enzyme inhibitor ramipril and vitamin E on atherosclerosis progression in high-risk patients.
Methods and Results—A
total of 732 patients 
55 years of age who had vascular disease or
diabetes and at least one other risk factor and who did not have heart
failure or a low left ventricular ejection fraction were randomly
assigned to receive ramipril 2.5 mg/d or 10 mg/d and vitamin E
(RRR-
-tocopheryl acetate) 400 IU/d or their matching
placebos. Average follow-up was 4.5 years. Atherosclerosis progression
was evaluated by B-mode carotid ultrasound. The progression slope of
the mean maximum carotid intimal medial thickness was 0.0217 mm/year in
the placebo group, 0.0180 mm/year in the ramipril 2.5 mg/d group, and
0.0137 mm/year in the ramipril 10 mg/d group
(P=0.033). There were no
differences in atherosclerosis progression rates between patients on
vitamin E and those on placebo.
Conclusions—Long-term treatment with ramipril had a beneficial effect on atherosclerosis progression. Vitamin E had a neutral effect on atherosclerosis progression.
Key Words: atherosclerosis • angiotensin • carotid arteries • ultrasonics
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T. J. Rabelink Cardiovascular risk in patients with renal disease: treating the risk or treating the risk factor? Nephrol. Dial. Transplant., January 1, 2004; 19(1): 23 - 26. [Full Text] [PDF]
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G. D. Laverman, G. Remuzzi, and P. Ruggenenti ACE Inhibition versus Angiotensin Receptor Blockade: Which Is Better for Renal and Cardiovascular Protection? J. Am. Soc. Nephrol., January 1, 2004; 15(90010): S64 - 70. [Abstract] [Full Text]
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M. L. Bots, G. W. Evans, W. A. Riley, and D. E. Grobbee Carotid Intima-Media Thickness Measurements in Intervention Studies: Design Options, Progression Rates, and Sample Size Considerations: A Point of View Stroke, December 1, 2003; 34(12): 2985 - 2994. [Abstract] [Full Text] [PDF]
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R. Arroyo-Espliguero, N. Mollichelli, P. Avanzas, E. Zouridakis, V. R Newey, D. K Nassiri, and J. C. Kaski Chronic inflammation and increased arterial stiffness in patients with cardiac syndrome X Eur. Heart J., November 2, 2003; 24(22): 2006 - 2011. [Abstract] [Full Text] [PDF]
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A. T Hirsch and D. Duprez The potential role of angiotensin-converting enzyme inhibition in peripheral arterial disease Vascular Medicine, November 1, 2003; 8(4): 273 - 278. [Abstract] [PDF]
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J. Galle and S. Seibold Has the time come to use antioxidant therapy in uraemic patients? Nephrol. Dial. Transplant., August 1, 2003; 18(8): 1452 - 1455. [Full Text] [PDF]
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G. Jennings New definitions in cardiovascular risk management: is it time for angiotensin II receptor blockers to become first-line medication? Eur. Heart J. Suppl., August 1, 2003; 5(suppl_F): F3 - F11. [Abstract] [PDF]
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S. S. Anand, Q. Yi, H. Gerstein, E. Lonn, R. Jacobs, V. Vuksan, K. Teo, B. Davis, P. Montague, and S. Yusuf Relationship of Metabolic Syndrome and Fibrinolytic Dysfunction to Cardiovascular Disease Circulation, July 29, 2003; 108(4): 420 - 425. [Abstract] [Full Text] [PDF]
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B. M. Singh and J. L. Mehta Interactions Between the Renin-Angiotensin System and Dyslipidemia: Relevance in the Therapy of Hypertension and Coronary Heart Disease Arch Intern Med, June 9, 2003; 163(11): 1296 - 1304. [Abstract] [Full Text] [PDF]
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L. E. Wagenknecht, D. Zaccaro, M. A. Espeland, A. J. Karter, D. H. O'Leary, and S. M. Haffner Diabetes and Progression of Carotid Atherosclerosis: The Insulin Resistance Atherosclerosis Study Arterioscler Thromb Vasc Biol, June 1, 2003; 23(6): 1035 - 1041. [Abstract] [Full Text] [PDF]
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D. S. Jacoby and D. J. Rader Renin-Angiotensin System and Atherothrombotic Disease: From Genes to Treatment Arch Intern Med, May 26, 2003; 163(10): 1155 - 1164. [Abstract] [Full Text] [PDF]
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C. Anderson Blood Pressure-Lowering for Secondary Prevention of Stroke: ACE Inhibition Is the Key Stroke, May 1, 2003; 34(5): 1333 - 1334. [Full Text] [PDF]
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S. Dhein, A. Kabat, A. Olbrich, P. Rosen, H. Schroder, and F.-W. Mohr Effect of Chronic Treatment with Vitamin E on Endothelial Dysfunction in a Type I in Vivo Diabetes Mellitus Model and in Vitro J. Pharmacol. Exp. Ther., April 1, 2003; 305(1): 114 - 122. [Abstract] [Full Text]
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J. V. Linseman and M. R. Bristow Drug Therapy and Heart Failure Prevention Circulation, March 11, 2003; 107(9): 1234 - 1236. [Full Text] [PDF]
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J. M. O. Arnold, S. Yusuf, J. Young, J. Mathew, D. Johnstone, A. Avezum, E. Lonn, J. Pogue, J. Bosch, and on behalf of the HOPE Investigators Prevention of Heart Failure in Patients in the Heart Outcomes Prevention Evaluation (HOPE) Study Circulation, March 11, 2003; 107(9): 1284 - 1290. [Abstract] [Full Text] [PDF]
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K. Fukuyama, T. Ichiki, K. Takeda, T. Tokunou, N. Iino, S. Masuda, M. Ishibashi, K. Egashira, H. Shimokawa, K. Hirano, et al. Downregulation of Vascular Angiotensin II Type 1 Receptor by Thyroid Hormone Hypertension, March 1, 2003; 41(3): 598 - 603. [Abstract] [Full Text] [PDF]
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R. M. Salonen, K. Nyyssonen, J. Kaikkonen, E. Porkkala-Sarataho, S. Voutilainen, T. H. Rissanen, T.-P. Tuomainen, V.-P. Valkonen, U. Ristonmaa, H.-M. Lakka, et al. Six-Year Effect of Combined Vitamin C and E Supplementation on Atherosclerotic Progression: The Antioxidant Supplementation in Atherosclerosis Prevention (ASAP) Study Circulation, February 25, 2003; 107(7): 947 - 953. [Abstract] [Full Text] [PDF]
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V. S. Monroe, R. A. Kerensky, E. Rivera, K. M. Smith, and C. J. Pepine Pharmacologic plaque passivation for the reduction of recurrent cardiac events in acute coronary syndromes J. Am. Coll. Cardiol., February 19, 2003; 41(4_Suppl_S): 23S - 30S. [Abstract] [Full Text] [PDF]
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E. G. Lakatta and D. Levy Arterial and Cardiac Aging: Major Shareholders in Cardiovascular Disease Enterprises: Part I: Aging Arteries: A "Set Up" for Vascular Disease Circulation, January 7, 2003; 107(1): 139 - 146. [Full Text] [PDF]
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H. C. Gerstein, S. Anand, Q. L. Yi, V. Vuksan, E. Lonn, K. Teo, K. Malmberg, M. McQueen, and S. Yusuf The Relationship Between Dysglycemia and Atherosclerosis in South Asian, Chinese, and European Individuals in Canada: A randomly sampled cross-sectional study Diabetes Care, January 1, 2003; 26(1): 144 - 149. [Abstract] [Full Text] [PDF]
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U. Landmesser and H. Drexler Oxidative stress, the renin-angiotensin system, and atherosclerosis Eur. Heart J. Suppl., January 1, 2003; 5(suppl_A): A3 - A7. [Abstract] [PDF]
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E. Lonn, H.C. Gerstein, M. Smieja, J.F.E. Mann, and S. Yusuf Mechanisms of cardiovascular risk reduction with ramipril: insights from HOPE and HOPE substudies Eur. Heart J. Suppl., January 1, 2003; 5(suppl_A): A43 - A48. [Abstract] [PDF]
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A. Zanchetti, M. G. Bond, M. Hennig, A. Neiss, G. Mancia, C. Dal Palu, L. Hansson, B. Magnani, K.-H. Rahn, J. L. Reid, et al. Calcium Antagonist Lacidipine Slows Down Progression of Asymptomatic Carotid Atherosclerosis: Principal Results of the European Lacidipine Study on Atherosclerosis (ELSA), a Randomized, Double-Blind, Long-Term Trial Circulation, November 5, 2002; 106(19): 2422 - 2427. [Abstract] [Full Text] [PDF]
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E. Lonn, S. Yusuf, B. Hoogwerf, J. Pogue, Q. Yi, B. Zinman, J. Bosch, G. Dagenais, J. F.E. Mann, and H. C. Gerstein Effects of Vitamin E on Cardiovascular and Microvascular Outcomes in High-Risk Patients With Diabetes: Results of the HOPE Study and MICRO-HOPE Substudy Diabetes Care, November 1, 2002; 25(11): 1919 - 1927. [Abstract] [Full Text] [PDF]
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