There is, however, no basis for adding or continuing estrogens in postmenopausal women with clinically evident SIHD in an effort to prevent or retard progression of their atherosclerotic disease. 4.4.2.5.2. Vitamin C, Vitamin E, and Beta-Carotene. Epide- miological and population studies have suggested that anti- oxidant vitamins, such as vitamin E, vitamin C, and beta- carotene, could lower cardiovascular risk.836,837 Controlled clinical trials, however, have failed to demonstrate a benefi- cial effect of antioxidant supplements on risk of cardiovas- cular morbidity and mortality.398,527,815 817 A meta-analysis of antioxidant vitamin studies examined 7 trials of vitamin E treatment and 8 trials of beta-carotene treatment with .1000 subjects in each. Most of these studies were performed in patients with CAD or at risk of CAD. Vitamin E had no effect on all-cause mortality or cardiovascular death.838 Beta- carotene led to a small but statistically significant increase in all-cause mortality and cardiovascular death. Thus, existing scientific evidence does not justify routine use of antioxidant supplements for the prevention or treatment of cardiovascular disease. 4.4.2.5.3. Folate and Vitamins B6 and B12. Prospective observational studies have demonstrated that the serum ho- mocysteine level is a strong, independent risk factor for ischemic events.839 841 Homocysteine levels can be lowered with folic acid or B-vitamins. Trials of folate and vitamin B supplementation, however, consistently have failed to dem- onstrate a decrease in cardiovascular morbidity or mortality rates. The VISP (Vitamin Intervention for Stroke Prevention) trial randomized patients with prior nondisabling stroke to varying doses of folic acid, B6, and B12. 