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.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
5R01AG013860-04
Application #
2899784
Study Section
Epidemiology and Disease Control Subcommittee 2 (EDC)
Project Start
1996-04-01
Project End
2002-03-31
Budget Start
1999-04-01
Budget End
2002-03-31
Support Year
4
Fiscal Year
1999
Total Cost
Indirect Cost
Name
University of Southern California
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
041544081
City
Los Angeles
State
CA
Country
United States
Zip Code
90089
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