Relation of Serum α- and γ-Tocopherol Levels to Cardiovascular Disease-Related Mortality Among Japanese Men and Women

Background: There is limited evidence regarding the relationship between serum tocopherol levels and cardiovascular disease. Methods: We conducted a nested case-control study as part of the Japan Collaborative Cohort Study for evaluation of cancer risk (JACC Study). Baseline serum samples were collected from 39 242 participants (age range, 40-79 years) between 1988 and 1990. During the 13-year follow-up, there were 530 stroke deaths (302 ischemic strokes and 210 hemorrhagic strokes) and 211 deaths from coronary heart disease. Controls were matched for sex, age, and area of residence. Results: Serum alpha-tocopherol level was not associated with any type of cardiovascular death in men; however, in women, it was inversely associated with total stroke mortality and hemorrhagic stroke mortality. The multivariate odds ratio (95% CI) for the highest versus the lowest quintile of serum alpha-tocopherol levels among women was 0.35 (0.16-0.77; P for trend = 0.009) for total stroke and 0.26 (0.07-0.97; P for trend = 0.048) for hemorrhagic stroke. Serum gamma-tocopherol was inversely associated with ischemic stroke mortality in men but positively associated with hemorrhagic stroke mortality in women. The respective multivariate odds ratios (95% CI) for the highest versus the lowest quintile and for a 1-standard deviation increment in gamma-tocopherol level were 0.48 (0.22-1.06; P for trend = 0.07) and 0.77 (0.58-1.02), respectively, for ischemic stroke in men and 3.10 (0.95-10.12; P for trend = 0.052) and 1.49 (1.04-2.13) for hemorrhagic stroke in women. Conclusions: Among women, hemorrhagic stroke mortality was inversely associated with serum a-tocopherol and positively associated with serum gamma-tocopherol. These findings are due in part to the antioxidative and antithrombotic activities of these tocopherols.