Effect of alpha-tocopherol and beta-carotene supplementation on coronary heart disease during the 6-year post-trial follow-up in the ATBC study.

AIMS: To evaluate the 6-year post-trial effects of alpha-tocopherol and beta-carotene supplementation on coronary heart disease (CHD) in the alpha-tocopherol, beta-carotene cancer prevention (ATBC) study. METHODS AND RESULTS: 29,133 male smokers, aged 50-69 years were randomised to receive alpha-tocopherol 50 mg, or beta-carotene 20 mg, or both, or placebo daily for 5-8 years. At the beginning of the post-trial follow-up, 23,144 men were still at risk for a first-ever major coronary event (MCE), and 1255 men with pre-trial history of myocardial infarction (MI) were at risk for MCE. Post-trial risk for MCE (n=2059) was 0.95 (95% confidence interval 0.87-1.04) among alpha-tocopherol recipients compared with non-recipients, and 1.14 (1.04-1.24) among beta-carotene recipients compared with non-recipients. The risk for non-fatal MI (n=993) was 0.96 (0.85-1.09) and 1.16 (1.03-1.32), and for fatal CHD (n=1066) 0.94 (0.83-1.06) and 1.11 (0.99-1.25), respectively. Among men with pre-trial MI no effects were observed in post-trial risk of MCE (n=257). CONCLUSION: beta-Carotene seemed to increase the post-trial risk of first-ever non-fatal MI but there is no plausible mechanism to support it. Our findings do not advocate the use of alpha-tocopherol or beta-carotene supplements in prevention of CHD among male smokers.

Flavonol and flavone intake and the risk of intermittent claudication in male smokers.

The objective of this study was to investigate the association between flavonol and flavone intake and the risk of intermittent claudication in male smokers. The study population consisted of participants of the Finnish alpha-Tocopherol, beta-Carotene Cancer Prevention (ATBC) Study, who were free of intermittent claudication at study entry. These 25,041 male smokers were 50-69 years old at baseline. Participants completed a validated dietary questionnaire at baseline. The occurrence of intermittent claudication was assessed by annual administration of the Rose questionnaire. During the median follow-up of 4.1 years, 2412 new cases of intermittent claudication were observed. Dietary intake of flavonols and flavones was inversely associated with the risk of intermittent claudication when adjusted for cardiovascular risk factors (relative risk, RR in the highest vs. lowest quintile of intake 0.86, 95% confidence interval, CI: 0.75-0.98, p for trend 0.007). However, after further adjustment for intakes of vitamins C and E and total carotenoids, the association was attenuated (RR: 0.93, 95% CI: 0.81-1.08, p for trend 0.12). The risk of intermittent claudication was lower among men in the highest quintile of vegetable consumption (RR: 0.78, 95% CI: 0.69-0.89, p for trend 0.0001) and among wine drinkers (RR: 0.63, 95% CI: 0.41-0.98). Adjustment for flavonol and flavone intake only marginally changed these associations. In conclusion, flavonol and flavone intake was not independently associated with the risk of intermittent claudication.

Postintervention effect of alpha tocopherol and beta carotene on different strokes: a 6-year follow-up of the Alpha Tocopherol, Beta Carotene Cancer Prevention Study.

BACKGROUND AND PURPOSE: In the Alpha Tocopherol, Beta Carotene Cancer Prevention Study, alpha tocopherol supplementation decreased risk of cerebral infarction by 14% (95% CI, -25% to -1%), and beta carotene increased risk of intracerebral hemorrhage by 62% (95% CI, 10% to 132%). We report here the 6-year postintervention effects of alpha tocopherol and beta carotene supplementation on stroke and its subtypes. METHODS: A total of 29,133 male smokers, aged 50 to 69 years, were randomized to receive 50 mg of alpha tocopherol, 20 mg of beta carotene, both, or placebo daily for 5 to 8 years. At the beginning of the post-trial follow-up, 24 382 men were still at risk for first-ever stroke. During the post-trial follow-up, 1327 men experienced a stroke: 1087 cerebral infarctions, 148 intracerebral hemorrhages, 64 subarachnoid hemorrhages, and 28 unspecified strokes. RESULTS: Post-trial risk for cerebral infarction was elevated among those who had received alpha tocopherol compared with those who had not (relative risk [RR], 1.13; 95% CI, 1.00 to 1.27), whereas beta carotene had no effect (RR, 0.97; 95% CI, 0.86 to 1.09). Alpha tocopherol supplementation was associated with a postintervention RR of 1.01 (95% CI, 0.73 to 1.39) for intracerebral hemorrhage and 1.38 (95% CI, 0.84 to 2.26) for subarachnoid hemorrhage. The corresponding RRs associated with beta carotene supplementation were 1.38 (95% CI, 0.99 to 1.91) and 1.09 (95% CI, 0.67 to 1.77), respectively. CONCLUSIONS: Neither alpha tocopherol nor beta carotene supplementation had any postintervention preventive effects on stroke. The post-trial increase in cerebral infarction risk among recipients of alpha tocopherol may present a rebound of the reduced risk of cerebral infarction during the intervention.