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 α-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 α-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 γ-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 γ-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 α-tocopherol and positively associated with serum γ-tocopherol. These findings are due in part to the antioxidative and antithrombotic activities of these tocopherols.