Effect of folic acid and B vitamins on risk of cardiovascular events and total mortality among women at high risk for cardiovascular disease: a randomized trial - PubMed (original) (raw)

Randomized Controlled Trial

Effect of folic acid and B vitamins on risk of cardiovascular events and total mortality among women at high risk for cardiovascular disease: a randomized trial

Christine M Albert et al. JAMA. 2008.

Abstract

Context: Recent randomized trials among patients with preexisting cardiovascular disease (CVD) have failed to support benefits of B-vitamin supplementation on cardiovascular risk. Observational data suggest benefits may be greater among women, yet women have been underrepresented in published randomized trials.

Objective: To test whether a combination of folic acid, vitamin B6, and vitamin B12 lowers risk of CVD among high-risk women with and without CVD.

Design, setting, and participants: Within an ongoing randomized trial of antioxidant vitamins, 5442 women who were US health professionals aged 42 years or older, with either a history of CVD or 3 or more coronary risk factors, were enrolled in a randomized, double-blind, placebo-controlled trial to receive a combination pill containing folic acid, vitamin B6, and vitamin B12 or a matching placebo, and were treated for 7.3 years from April 1998 through July 2005.

Intervention: Daily intake of a combination pill of 2.5 mg of folic acid, 50 mg of vitamin B6, and 1 mg of vitamin B12.

Main outcome measures: A composite outcome of myocardial infarction, stroke, coronary revascularization, or CVD mortality.

Results: Compared with placebo, a total of 796 women experienced a confirmed CVD event (406 in the active group and 390 in the placebo group). Patients receiving active vitamin treatment had similar risk for the composite CVD primary end point (226.9/10,000 person-years vs 219.2/10,000 person-years for the active vs placebo group; relative risk [RR], 1.03; 95% confidence interval [CI], 0.90-1.19; P = .65), as well as for the secondary outcomes including myocardial infarction (34.5/10,000 person-years vs 39.5/10,000 person-years; RR, 0.87; 95% CI, 0.63-1.22; P = .42), stroke (41.9/10,000 person-years vs 36.8/10,000 person-years; RR, 1.14; 95% CI, 0.82-1.57; P = .44), and CVD mortality (50.3/10,000 person-years vs 49.6/10,000 person-years; RR, 1.01; 95% CI, 0.76-1.35; P = .93). In a blood substudy, geometric mean plasma homocysteine level was decreased by 18.5% (95% CI, 12.5%-24.1%; P < .001) in the active group (n = 150) over that observed in the placebo group (n = 150), for a difference of 2.27 micromol/L (95% CI, 1.54-2.96 micromol/L).

Conclusion: After 7.3 years of treatment and follow-up, a combination pill of folic acid, vitamin B6, and vitamin B12 did not reduce a combined end point of total cardiovascular events among high-risk women, despite significant homocysteine lowering.

Trial registration: clinicaltrials.gov Identifier: NCT00000541.

PubMed Disclaimer

Figures

Figure 1

Figure 1

Flow Diagram of the Folic Acid/Vitamin B6/Vitamin B12 Component of the Women’s Antioxidant and Folic Acid Cardiovascular Study. * Mortality information was complete for over 99% of person-years of follow-up.

Figure 2

Figure 2

Cumulative incidence of major vascular disease (myocardial infarction, stroke, coronary revascularization, or cardiovascular death), by randomized folic acid and B-vitamin intervention in the Women’s Antioxidant and Folic Acid Study (WAFACS). P-value is from log-rank test.

Comment in

Similar articles

Cited by

References

    1. Homocysteine Studies Collaboration. Homocysteine and risk of ischemic heart disease and stroke: a meta-analysis. JAMA. 2002;288(16):2015–22. - PubMed
    1. Homocysteine Lowering Trialists’ Collaboration. Lowering blood homocysteine with folic acid based supplements: meta-analysis of randomised trials. BMJ. 1998;316(7135):894–8. - PMC - PubMed
    1. Bazzano LA, Reynolds K, Holder KN, He J. Effect of folic acid supplementation on risk of cardiovascular diseases: a meta-analysis of randomized controlled trials. JAMA. 2006;296(22):2720–6. - PubMed
    1. Carlsson CM. Lowering homocysteine for stroke prevention. Lancet. 2007;369(9576):1841–2. - PubMed
    1. Lonn E, Yusuf S, Arnold MJ, et al. Homocysteine lowering with folic acid and B vitamins in vascular disease. N Engl J Med. 2006;354(15):1567–77. - PubMed

Publication types

MeSH terms

Substances

Grants and funding

LinkOut - more resources