This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hosomi, N. Articles by Koziol, J. A. Search for Related Content PubMed PubMed Citation Articles by Hosomi, N. Articles by Koziol, J. A. Related Collections Type 2 diabetes Carotid Stenosis Doppler ultrasound, Transcranial Doppler etc. Risk Factors for Stroke

(Stroke. 2001;32:1539.)
© 2001 American Heart Association, Inc.

Original Contributions

Angiotensin-Converting Enzyme Inhibition With Enalapril Slows Progressive Intima-Media Thickening of the Common Carotid Artery in Patients With Non–Insulin-Dependent Diabetes Mellitus

Naohisa Hosomi, MD, PhD; Katsufumi Mizushige, MD, PhD; Hideo Ohyama, MD, PhD; Tsutomu Takahashi, MD, PhD; Masaya Kitadai, MD, PhD; Yoshio Hatanaka, MD, PhD; Hirohide Matsuo, MD, PhD; Masakazu Kohno, MD, PhD James A. Koziol, PhD

From the Second Department of Internal Medicine, Kagawa Medical University School of Medicine, Kagawa, Japan (N.H., K.M., H.O., T.T., H.M., M.K.); Department of Internal Medicine, Takamatsu National Hospital, Kagawa, Japan (N.H., M.K., Y.H.); and Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, Calif (N.H., J.A.K.).

Background and Purpose—Whether angiotensin-converting enzyme (ACE) inhibitors have any clinically significant antiatherogenic effects in humans remains unproven. We undertook a prospective randomized clinical trial of 98 patients with non–insulin-dependent diabetes mellitus (NIDDM) to examine the efficacy of ACE inhibition with enalapril for preventing intima-media (IM) thickening of the carotid wall as measured ultrasonographically.

Methods—Ninety-eight NIDDM patients were randomly assigned either to enalapril at 10 mg/d (n=48) or to a control group (n=50); the planned duration of the trial was 2 years. All patients were seen at baseline (study entry) and 2 subsequent formal annual evaluations, in addition to standard clinical management for NIDDM. IM thickening and vascular lumen diameters were determined for all patients on the basis of baseline and 2 subsequent annual evaluations with carotid ultrasonography. We performed an intent-to-treat analysis to assess changes in IM thickening over the course of the study.

Results—Annual IM thickening measurements of the right and left common carotid arteries were 0.01±0.02 and 0.01±0.02 mm/y in the enalapril-treated group and 0.02±0.03 and 0.02±0.02 mm/y in the control group, respectively (P<0.05). From regression analysis, annual IM thickening was found to be predicted by enalapril use, sex, and insulin use (F_3,94=3.86, P=0.012). When we controlled for these other variables, enalapril use reduced annual IM thickening of right and left common carotid arteries by 0.01±0.004 mm/y relative to the control group over the course of this study.

Conclusions—Long-term treatment with an ACE inhibitor (enalapril) slows progressive IM thickening of the common carotid artery in NIDDM patients.

Key Words: angiotensin converting enzyme inhibitors • atherosclerosis • carotid artery • diabetes • ultrasonography

This article has been cited by other articles:

				T. Naya, N. Hosomi, H. Ohyama, S.-I. Ichihara, C. R. Ban, T. Takahashi, T. Taminato, A. Feng, M. Kohno, and J. A. Koziol Smoking, Fasting Serum Insulin, and Obesity Are the Predictors of Carotid Atherosclerosis in Relatively Young Subjects Angiology, January 1, 2008; 58(6): 677 - 684. [Abstract] [PDF]

				J.-H. Oak and H. Cai Attenuation of Angiotensin II Signaling Recouples eNOS and Inhibits Nonendothelial NOX Activity in Diabetic Mice Diabetes, January 1, 2007; 56(1): 118 - 126. [Abstract] [Full Text] [PDF]

				H. Yokoyama, N. Katakami, and Y. Yamasaki Recent Advances of Intervention to Inhibit Progression of Carotid Intima-Media Thickness in Patients With Type 2 Diabetes Mellitus Stroke, September 1, 2006; 37(9): 2420 - 2427. [Abstract] [Full Text] [PDF]

				J.-G. Wang, J. A. Staessen, Y. Li, L. M. Van Bortel, T. Nawrot, R. Fagard, F. H. Messerli, and M. Safar Carotid Intima-Media Thickness and Antihypertensive Treatment: A Meta-Analysis of Randomized Controlled Trials Stroke, July 1, 2006; 37(7): 1933 - 1940. [Abstract] [Full Text] [PDF]

				T. S. Hermann, W. Li, H. Dominguez, N. Ihlemann, C. Rask-Madsen, A. Major-Pedersen, D. B. Nielsen, K. W. Hansen, M. Hawkins, L. Kober, et al. Quinapril Treatment Increases Insulin-Stimulated Endothelial Function and Adiponectin Gene Expression in Patients with Type 2 Diabetes J. Clin. Endocrinol. Metab., March 1, 2006; 91(3): 1001 - 1008. [Abstract] [Full Text] [PDF]

				M.R. Langenfeld, T. Forst, C. Hohberg, P. Kann, G. Lubben, T. Konrad, S.D. Fullert, C. Sachara, and A. Pfutzner Pioglitazone Decreases Carotid Intima-Media Thickness Independently of Glycemic Control in Patients With Type 2 Diabetes Mellitus: Results From a Controlled Randomized Study Circulation, May 17, 2005; 111(19): 2525 - 2531. [Abstract] [Full Text] [PDF]

				M. Hanefeld, J. L. Chiasson, C. Koehler, E. Henkel, F. Schaper, and T. Temelkova-Kurktschiev Acarbose Slows Progression of Intima-Media Thickness of the Carotid Arteries in Subjects With Impaired Glucose Tolerance Stroke, May 1, 2004; 35(5): 1073 - 1078. [Abstract] [Full Text] [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]