Antioxidant vitamins and coronary artery disease risk.

Coronary artery disease (CAD) remains by far the leading killer of men and women in the United States, despite a 2% per year decline over the past 2 decades. While CAD becomes the leading cause of death in U.S. women after 60, it becomes so in men after age 40. Heart disease is responsible for one of every three deaths in women as well as men. Thus, any intervention that can reduce CAD risks could have a tremendous public health impact among U.S. adults. Over the past several decades, the atherogenic potential of low density lipoprotein (LDL) cholesterol has been clearly identified. Recent evidence suggests that oxidation of LDL may enhance its atherogenicity, raising the possibility that antioxidant vitamins, which inhibit the oxidation of LDL, may reduce the risk of CAD. Although antioxidants can preserve endothelial function, inhibit platelet aggregability, and reduce atherosclerotic plaque progression in animals, whether supplementation with antioxidant vitamins will reduce the risk of CAD in humans remains unclear. The epidemiologic studies that have explored the antioxidant vitamin hypothesis in humans have included descriptive and cross-sectional studies, analytic investigation using case-control and prospective cohort study designs, as well as a few small trials in secondary prevention. The findings from these studies are not totally consistent, but generally support the hypothesis that antioxidant vitamins may reduce risk of CAD. At present, therefore, antioxidant vitamins represent a promising, but as yet unproven, means to decrease risks of CAD. Several large-scale randomized trials will provide reliable evidence on this question over the next several years. In primary prevention, the recently begun Women's Health Study of 40,000 female health professionals is testing alternate-day doses of beta-carotene (50 mg) and vitamin E (600 mg), and the ongoing Physicians' Health Study of > 22,000 male physicians is also testing a 50 mg combination of beta-carotene, vitamin E, and vitamin C among approximately 8,000 women not eligible for the Women's Health Study due to a prior history of cardiovascular disease. These and other trials will provide reliable, direct evidence concerning the role of antioxidant vitamins in the primary and secondary prevention of cardiovascular disease in women. Such data are crucial both for individual clinical decision making as well as for formulating rational public health policies.