International Task Force for Prevention of
Coronary Heart Disease
CORONARY HEART DISEASE: REDUCING THE RISK
Oxidation of LDL appears to be a necessary step in foam cell formation in the arterial wall and hence in atherogenesis (see also 2.8.3.2, Oxidized LDL). This has raised the possibility that use of antioxidants might reduce the risk of atherosclerotic diseases, as has been shown in experimental animals. Observational studies of antioxidants have concentrated on the use of water soluble vitamin C and the fat soluble vitamins A and E.
In the Iowa Women's Health Study 53, intake of vitamins A, E and C in diets and vitamin supplements was assessed in 35,000 middle-aged women. An inverse association was found between coronary heart disease and the intake of vitamin E in food, but not in supplements. In the Physicians' Health Study of 40,000 physicians54 and in the Nurses' Health Study of 87,000 female nurses 55, however, intake of vitamin E supplements was also associated with a reduced risk of CHD. A problem of all such studies, however, is the possible bias of self selection: vitamin E users might smoke less, be less obese or take more exercise than the general population. Mathematical models can only partially correct such potential biases. For this reason, large blinded randomized controlled intervention trials of anti-oxidants are necessary.
A general deficiency of many of the randomized controlled trials of antioxidants is that they were primarily designed to investigate the effects of antioxidant therapy on the incidence of cancer, especially in smokers. This may have led to selection of samples inappropriate for monitoring cardiovascular endpoints. For example, in a Finnish trial of 29,000 male smokers56, a supplement of only 50 mg vitamin E and/or 20 mg beta carotene (vitamin A) per day over 5 to 8 years did not reduce the incidence of lung cancer, the primary endpoint of the trial. In this trial, more CHD deaths occurred in the beta-carotene group than in controls. Similar effects of beta carotene intake have been reported in another trial.
The US Health Professionals Study also investigated the effect of beta carotene supplements in a well nourished population with low rates of coronary disease and cancer 57, 58. Twenty-two thousand male physicians were allocated to one of four therapies: beta-carotene 50 mg + acetyl salicylic acid 325 mg on alternate days; beta-carotene 50 mg + placebo on alternate days; acetyl salicylic acid 325 mg + beta-carotene placebo on alternate days; or placebo alone. After 12 years of follow-up, no difference in cardiovascular disease or cancer rates was seen between the treatment and placebo groups. The Cambridge Heart AntiOxidant Study (CHAOS) was a secondary prevention study of 2,000 men with angiographically proven coronary atherosclerosis 59. The actively treated group received 400-800 IU vitamin E and the placebo group soy bean capsules. The supplementation resulted almost doubled the plasma alpha-tocopherol concentration. There were significantly fewer non-fatal myocardial infarctions (14 vs 41, p < 0.0001) in the vitamin E treated group; but an adverse trend for cardiovascular deaths was also seen. The trial was numerically underpowered and was stopped prematurely. The results of this trial await confirmation.
Thus, both epidemiological and interventional studies provide preliminary evidence that antioxidants, either as dietary constituents or as supplements, may help to prevent development of coronary artery disease. However, much of the data from both sources is inconsistent. For this reason, no recommendations on the use of antioxidant supplementation can be made at present. The best advice currently is to eat abundant fresh vegetables, wholegrain cereal, and moderate amounts of vegetable oils as olive oil or rape seed oil (good sources of vitamin E), and fruit, particularly citrus fruits, which are rich in vitamin C.