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(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)

Eva M. Lonn, MD, MSc; Salim Yusuf, MBBS, DPhil; Vladimir Dzavik, MD; C. Ian Doris, MBChB; Qilong Yi, PhD; Sandra Smith, RDMS; Anne Moore-Cox, RDMS; Jackie Bosch, MSc; Ward A. Riley, PhD; Koon K. Teo, MB, PhD; for the SECURE Investigators

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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				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]

				A. D Vuong and L. G Annis Ramipril for the Prevention and Treatment of Cardiovascular Disease Ann. Pharmacother., March 1, 2003; 37(3): 412 - 419. [Abstract] [Full Text] [PDF]

				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]

				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]

				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]

				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]

				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]

				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]

				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]

				H. Vlassara, W. Cai, J. Crandall, T. Goldberg, R. Oberstein, V. Dardaine, M. Peppa, and E. J. Rayfield Inflammatory mediators are induced by dietary glycotoxins, a major risk factor for diabetic angiopathy PNAS, November 26, 2002; 99(24): 15596 - 15601. [Abstract] [Full Text] [PDF]

				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]

				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]

				J. R. Crouse III, R. Tang, M. A. Espeland, J. G. Terry, T. Morgan, and M. Mercuri Associations of Extracranial Carotid Atherosclerosis Progression With Coronary Status and Risk Factors in Patients With and Without Coronary Artery Disease Circulation, October 15, 2002; 106(16): 2061 - 2066. [Abstract] [Full Text] [PDF]

				A. Fisher and J. E. Morley Editorial: Antiaging Medicine: The Good, the Bad, and the Ugly J. Gerontol. A Biol. Sci. Med. Sci., October 1, 2002; 57(10): M636 - 639. [Full Text] [PDF]

				H. N. Hodis, W. J. Mack, L. LaBree, P. R. Mahrer, A. Sevanian, C.-r. Liu, C.-h. Liu, J. Hwang, R. H. Selzer, S. P. Azen, et al. Alpha-Tocopherol Supplementation in Healthy Individuals Reduces Low-Density Lipoprotein Oxidation but Not Atherosclerosis: The Vitamin E Atherosclerosis Prevention Study (VEAPS) Circulation, September 17, 2002; 106(12): 1453 - 1459. [Abstract] [Full Text] [PDF]

				A. Iannuzzi, E. Celentano, S. Panico, R. Galasso, G. Covetti, L. Sacchetti, F. Zarrilli, M. De Michele, and P. Rubba Dietary and circulating antioxidant vitamins in relation to carotid plaques in middle-aged women Am. J. Clinical Nutrition, September 1, 2002; 76(3): 582 - 587. [Abstract] [Full Text] [PDF]

				S. Achenbach, D. Ropers, K. Pohle, A. Leber, C. Thilo, A. Knez, T. Menendez, R. Maeffert, M. Kusus, M. Regenfus, et al. Influence of Lipid-Lowering Therapy on the Progression of Coronary Artery Calcification: A Prospective Evaluation Circulation, August 27, 2002; 106(9): 1077 - 1082. [Abstract] [Full Text] [PDF]