Despite identification of modifiable risk factors for development and progression of atherosclerosis, coronary heart disease (CHD) remains the single most important chronic disease in the United States (US). Early intervention of atherosclerotic disease may be necessary to accomplish the national goal of reducing CHD mortality. A large body of data from animal and epidemiological studies provide convincing evidence that antioxidant vitamins can reduce formation and progression of atherosclerosis. Vitamin E supplementation has shown the most consistent association with reduction in CHD risk in asymptomatic men and women. Recent serial quantitative coronary angiographic (QCA) as well as B-mode ultrasonographic common carotid artery (CCA) intima media thickness (IMT) measurements from the Cholesterol Lowering Atherosclerosis Study (CLAS) and the Monitored Atherosclerosis Regression Study (MARS) demonstrate that supplementary vitamin E intake reduces progression of atherosclerosis by 50% to 80% over a 2 year period. Vitamin E supplementation provides a promising approach for primary prevention of CHD since it is natural, safe, highly tolerable, and inexpensive. Thus, the public health impact of providing direct evidence of the efficacy of vitamin E supplementation in reducing progression of atherosclerosis will have immense implications for population based interventional strategies for primary prevention of CHD. Primary prevention trials which use CHD event outcomes typically require 5 to 10 thousand individuals followed for 5 to 10 years to detect treatment differences. Serial elective coronary angiography cannot be ethically performed in primary prevention trials because of unacceptable risk of complications to asymptomatic individuals. However, automated computerized edge detection image analysis of B-mode ultrasound images of CCA far wall IMT reduces ultrasonographic measurement error and makes it feasible to non- invasively test the efficacy of vitamin E supplementation on early atherosclerosis progression in a substantially reduced sample size (200 subjects) and study duration (2 years) required to conduct a primary prevention intervention trial at no risk to individuals free of CHD. Therefore, the investigators propose a SINGLE-CENTER, 2-year, randomized, placebo-controlled, double-blind, non-invasive arterial imaging primary prevention trial with vitamin E supplementation in healthy men and women 35 to 75 years old with LDL-C levels between 100 mg/dL and 200 mg/dL. Treatment arms will be DL-a-tocopherol 400 IU/day versus placebo; both arms will receive a low fat-low cholesterol diet (NCEP Step I). Primary trial outcome measure will be rate of change of distal CCA far wall IMT in computer image processed B-mode ultrasonograms. The investigators state that this non-invasive vascular end point measure has shown therapy benefit in their two previous coronary angiographic/carotid ultrasonographic clinical trails and correlates with carotid and coronary artery atherosclerosis as determined by angiography.

National Institute of Health (NIH)
National Institute on Aging (NIA)
Research Project (R01)
Project #
Application #
Study Section
Epidemiology and Disease Control Subcommittee 2 (EDC)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Southern California
Internal Medicine/Medicine
Schools of Medicine
Los Angeles
United States
Zip Code
K├╝nzli, Nino; Jerrett, Michael; Garcia-Esteban, Raquel et al. (2010) Ambient air pollution and the progression of atherosclerosis in adults. PLoS One 5:e9096
El-Shahawy, Mohamed; Noureddin, Mazen; Abdullah, Hesham et al. (2007) Platelet FcgammaRIIA receptor surface expression is increased in patients with ESRD and is associated with atherosclerotic cardiovascular events. Am J Kidney Dis 49:127-34
Kunzli, Nino; Jerrett, Michael; Mack, Wendy J et al. (2005) Ambient air pollution and atherosclerosis in Los Angeles. Environ Health Perspect 113:201-6
Mack, Wendy J; Islam, Talat; Lee, Zenaida et al. (2003) Environmental tobacco smoke and carotid arterial stiffness. Prev Med 37:148-54
Hodis, Howard N; Mack, Wendy J; LaBree, Laurie et al. (2002) Alpha-tocopherol supplementation in healthy individuals reduces low-density lipoprotein oxidation but not atherosclerosis: the Vitamin E Atherosclerosis Prevention Study (VEAPS). Circulation 106:1453-9
Calverley, David C; Brass, Elizabeth; Hacker, Michele R et al. (2002) Potential role of platelet FcgammaRIIA in collagen-mediated platelet activation associated with atherothrombosis. Atherosclerosis 164:261-7
Selzer, R H; Mack, W J; Lee, P L et al. (2001) Improved common carotid elasticity and intima-media thickness measurements from computer analysis of sequential ultrasound frames. Atherosclerosis 154:185-93
Azen, S P; Qian, D; Mack, W J et al. (1996) Effect of supplementary antioxidant vitamin intake on carotid arterial wall intima-media thickness in a controlled clinical trial of cholesterol lowering. Circulation 94:2369-72