BETA CAROTENE, VITAMIN E ROLE IN CARDIOVASCULAR AND CANCER PREVENTION

BETA CAROTENE, VITAMIN E ROLE IN CARDIOVASCULAR AND CANCER PREVENTION will be studied in the 40,000-participant Women's Health Study, which began enrollment last fall, Julie Buring, ScD, Harvard Medical School, reported at the Council for Responsible Nutrition's annual meeting on Sept. 22. Currently, 13,000 women aged 45 and over are participating in the study with full enrollment expected to be completed by next summer. Buring, who is the principal investigator, explained that the randomized double-blind placebo-controlled trial is designed to evaluate the benefits and risks of beta carotene, vitamin E and low dose aspirin on cardiovascular disease and cancer in apparently healthy U.S. female nurses. By using a two-by-two-by-two factorial design, Buring explained, the Women's Health Study will examine a total of eight treatment groups with patients receiving either aspirin 100 mg on alternate days or placebo; 50 mg beta carotene on alternate days or placebo; and 600 IUs vitamin E or placebo. The "chief advantage of this design is our ability to answer several important and timely research questions basically for the price of one study," Buring said. Another advantage of this design, she added, is "its ability to assess the possible interaction between" any of the three agents tested in the study. Commenting on the cost of the trial, Buring noted that, at $ 80 per participant per year, the study is "about as cost efficient as I think you could do a primary prevention trial." Miles is providing the aspirin for the study while BASF and the Natural Source Vitamin E Association are providing the beta carotene and vitamin-E supplements, respectively. Commenting on the limitations of earlier questionnaire-based studies, Buring asserted that "regardless of the size of these studies or the quality of the data collected, there is residual concern . . . because it is inherent in all observational studies that the participants have self-selected to vitamin use." One concern in an observational study, Buring noted, is that they are "limited in their ability to . . . definitively demonstrate that it is one particular vitamin or more than one vitamin that is reducing this risk." To compensate for this, she explained, "you need a randomized trial where all the risk factors both known and unknown will be evenly divided between the groups and when you are done, there is no doubt" that it is a particular "agent that is responsible for the lower risk of coronary disease and not some other factor that you simply could not measure." In addition, she pointed out that there is the concern that a "null finding" or a lack of statistical significance could be misinterpreted. Buring also announced that her research group was "just funded" to conduct a randomized trial of antioxidant vitamins in the secondary prevention or treatment of cardiovascular disease. Funded by the National Heart, Lung and Blood Institute for five years, study recruitment is expected to commence in January 1994. The study will enroll 8,000 women who were not eligible for the Women's Health Study "due to a prior history of cardiovascular disease," Buring reported. The trial, which will be called the Women's Antioxidant Cardiovascular Disease Study, will examine the potential effect of vitamin E, vitamin C and beta carotene on subsequent cardiac events. Buring also outlined five other primary prevention trials looking at the potential benefit of antioxidant vitamins that are currently under way. The CARET study is testing beta carotene among 18,000 individuals at high risk for lung cancer due to occupational asbestos exposure, she said. The ATBC cancer prevention trial, Buring reported, is assessing the effects of beta carotene and vitamin E in Finnish male smokers and will be completed by the end of the year. A third study -- the su.vi.max trial -- is studying beta carotene, vitamin E, vitamin C as well as zinc in healthy French men and women, she noted. And the PQRST trial is testing the effect of antioxidant vitamins on patients with hypercholesterolemia. Buring also outlined some preliminary findings of the Physician's Health Study, which Buring included among the six ongoing prevention trials testing antioxidant vitamins. The data from this study, conducted by Gaziano, et al., Buring reported, were really the first randomized trial data in the general population that suggested that antioxidants can reduce the risk of cardiovascular disease. The primary prevention trial, conducted among 22,071 U.S. male physicians who were between the ages of 40 and 84 in 1982, was designed to evaluate two prevention hypotheses: whether aspirin 325 mg taken every other day could lower the risk of cardiovascular disease; and whether beta carotene 50 mg on alternate days could reduce the incidence of cancer. The aspirin component of the trial was terminated in January 1988 when data clearly showed a reduction in risk from a first heart attack. The beta carotene component is scheduled to end in 1995. Buring's group looked at a subgroup of 333 men in the aspirin component of the trial in order to make a preliminary evaluation as to the possible effects of beta carotene on cardiovascular events and noted that beta carotene may have an additive effect since no heart attacks were reported in the treatment group taking both agents. Although the trial in its entirety has not been published, Gaziano et al. reported the findings of this subgroup in an abstract printed in an October 1990 issue of Circulation: those assigned 50 mg beta carotene on alternate days had a "44% reduction in all major coronary events defined as myocardial infarction, revascularization or cardiac death and a 49% reduction in all major vascular events defined as stroke, myocardial infarction, revascularization or cardiovascular death after adjustment for age and aspirin assignment." Sitting on a panel with Buring were Eric Rimm, principal investigator of the Health Professional Follow-Up Study, and Meir Stampfer, who conducted the Nurses' Health Study ("The Tan Sheet" May 24, p. 10). Buring said that the data from the Physicians Health Study add "important information to the totality of evidence that includes" the "high quality" observational data in the Nurses' Health Study and the Health Professional Follow-Up Study."