Does popping vitamins help men’s heart health?

1 November 2010

Does taking common antioxidants like vitamin E and C reduce the risk of heart disease is the question explored by this month’s clinically-appraised topic.

The antioxidants vitamin E and vitamin C when used for primary prevention of heart disease do not reduce cardiovascular events in adult males.web vitamins

Browsing at a pharmacy while awaiting a prescription, you notice information that suggests vitamin E improves heart health. You are sure that you have seen solid evidence that vitamin E does not prevent heart disease, so you wonder what can be meant by “heart health”. To reassure yourself you want to check the evidence on vitamin E and cardiovascular disease.

Among adults, does supplementation with vitamin E reduce the risk of cardiovascular events?

Sesso H D, et al. Vitamins E and C in the prevention of cardiovascular disease in men. JAMA 2008; 300: 2123-33.

Blinded, factorial, randomised controlled trial conducted with male physicians in the United States from 1997 to 2007. More than 18,600 physicians who participated in a previous study were invited into this second study; at the same time 254,597 new physicians were asked to participate. Inclusion criterion was willingness to forego any current regimen of multivitamins or supplements containing more than the 100% recommended daily intake of vitamins. Participants could have a pre-existing history of myocardial infarction, stroke or cancer. Exclusion criteria were history of cirrhosis, active liver disease, taking anticoagulants, or reporting a serious illness that might preclude participation. 11,128 new physicians were eligible and took part in the 12 week run-in phase to exclude non-adherent participants; 7000 new physicians in addition to the 7641 physicians from the previous study were randomised. Participants were sent monthly calendar packs for vitamin E or matching placebo and vitamin C or matching placebo every six months for the first year and then annually thereafter.

The four treatment groups:
Active vitamin E and active vitamin C (n=3656): 400 IU vitamin E every second day and 500mg vitamin C daily.
Active vitamin E and placebo vitamin C (n=3659): 400 IU vitamin E every second day and placebo vitamin C every day.
Placebo vitamin E and active vitamin C (n=3673): Placebo vitamin E every second day and 500mg vitamin C daily.
Placebo vitamin E and placebo vitamin C (n=3653): Placebo vitamin E every second day and placebo vitamin C daily.

Composite end-point of major cardiovascular events (non-fatal stroke, non-fatal myocardial infarction) and cardiovascular mortality as determined by blinded adjudication committee examination of the participants’ clinical records for nonfatal events and death certificate and/or autopsy reports for fatal events.

Block randomisation with block size of 16 used to stratify for age, prior diagnosis of cardiovascular disease, prior diagnosis of cancer, and beta-carotene assignment in the previous study. Allocation concealment not described in this paper, although reported elsewhere, but presumably achieved through use of matching packaging and unique coding of packs. Loss to follow up was 312 (2%) overall and was similar in all four treatment arms. Analysis was by intention-to-treat. Participants and individuals delivering the interventions, investigators and adjudication committee were blinded to the interventions. The groups were balanced at baseline. Overall impression – a high quality study.

Participants at baseline were aged on average 64 years, with a mean BMI 26. 56% had never smoked, 61% exercised more than once per week, and only 23% were not currently using aspirin. The frequency of diabetes, hypertension, hypercholestraemia, family history of early myocardial infarction and self-reported cardiovascular disease was similar across the four groups. Median follow-up time was eight years and 1661 men died during follow-up. Vitamin E and vitamin C did not reduce cardiovascular events (see table), either when all events were combined or when events were considered singularly (total myocardial infarction, total stroke or total cardiac mortality). When stroke subgroups were considered, using vitamin E appeared to increase the risk of haemorrhagic stroke (hazard ratio 1.74, 95%CI 1.04–2.91).

Vitamin supplements provided by BASF Corporation, but the supplier had no part in the design, conduct or analysis of the study.
Study had 80% power to determine a 16% relative risk reduction.
Adherence with vitamin E at four and eight years was 78% and 77% respectively and 78% at both time points for vitamin C. 

Dr Andrew Jull, RN PhD, associate professor
(School of Nursing); nurse advisor – quality,
Auckland District Health Board.

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