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Reduction in Carotid Arterial Wall Thickness Using Lovastatin and Dietary Therapy: A Randomized, Controlled Clinical Trial

Howard N. Hodis, MD; Wendy J. Mack, PhD; Laurie LaBree, MS; Robert H. Selzer, MS; Chao-ran Liu, MD; Ci-hua Liu, MD; Petar Alaupovic, PhD; Helenann Kwong-Fu, MS; and Stanley P. Azen, PhD
[+] Article and Author Information

From the University of Southern California School of Medicine, Los Angeles, California, and the Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma. Grant Support: In part by the National Heart, Lung, and Blood Institute through investigator-initiated grants RO1-HL-49885, RO1-HL-45005, and RO1-HL-48399. Requests for Reprints: Howard N. Hodis, MD, Atherosclerosis Research Unit, Division of Cardiology, University of Southern California School of Medicine, 2250 Alcazar Street, CSC 132, Los Angeles, CA 90033. Current Author Addresses: Drs. Hodis, Liu, and Liu: Atherosclerosis Research Unit, Division of Cardiology, University of Southern California School of Medicine, 2250 Alcazar Street, CSC 132, Los Angeles, CA 90033.


Copyright ©2004 by the American College of Physicians


Ann Intern Med. 1996;124(6):548-556. doi:10.7326/0003-4819-124-6-199603150-00002
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Objective: To assess the effects of lipid-lowering therapy on the progression of early, preintrusive carotid arterial atherosclerosis.

Design: Randomized, double-blind, placebo-controlled, serial carotid arterial imaging trial.

Setting: University Atherosclerosis Research Unit.

Patients: 188 patients from the Monitored Atherosclerosis Regression Study who were 37 to 67 years of age and had angiographically defined coronary artery disease.

Intervention: Cholesterol-lowering diet plus placebo or lovastatin, 80 mg/d.

Measurements: High-resolution B-mode ultrasonographic quantification of the combined thickness of the distal common carotid arterial far wall intima-media complex (carotid arterial intima-media thickness) at baseline and every 6 months for as long as 4 years.

Results: The annual rate of change in carotid arterial intima-media thickness differed significantly between the lovastatin group and the placebo group at 2 and 4 years (P < 0.001). Patients receiving lovastatin had consistent reduction of the intima-media thickness (P < 0.001 as early as 1 year), whereas patients receiving placebo had consistent increase of the intima-media thickness at 2 and 4 years (P < 0.02). On-trial levels of low-density lipoprotein cholesterol, triglycerides, and apolipoproteins B, C-III, and E correlated significantly with the annual rate of change in carotid arterial intima-media thickness (P < 0.001).

Conclusion: Lipid-lowering therapy reverses the progression of early, preintrusive atherosclerosis of the carotid artery. Both cholesterol-rich and triglyceride-rich lipoproteins correlate with the progression of early, preintrusive atherosclerosis of the carotid artery. These findings, together with earlier reports of the effects of lovastatin therapy on the progression of atherosclerosis of the coronary arteries, indicate that carotid arterial far wall intima-media thickness is a useful end point for anti-atherosclerosis trials.

Figures

Grahic Jump Location
Figure 1.
Change in the combined thickness of the distal common carotid arterial far wall intima–media complex (IMT) stratified by randomized treatment.

Curves represent carotid arterial intima–media thickness regressed on time (months) since the baseline ultrasonographic examination in the placebo group (+) and the lovastatin group (·).

Grahic Jump Location

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