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.
Figures
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
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
- Homocysteine-lowering B vitamin therapy in cardiovascular prevention--wrong again?
Lonn E. Lonn E. JAMA. 2008 May 7;299(17):2086-7. doi: 10.1001/jama.299.17.2086. JAMA. 2008. PMID: 18460669 No abstract available. - Can folic acid and vitamin B lower CVD risk in high-risk women?
[No authors listed] [No authors listed] J Fam Pract. 2008 Aug;57(8):507-8. J Fam Pract. 2008. PMID: 18697288 No abstract available. - Effect of folic acid and B vitamins on cardiovascular disease in women.
Akilzhanova A, Takamura N, Yamashita S. Akilzhanova A, et al. JAMA. 2008 Sep 24;300(12):1409-10; author reply 1410. doi: 10.1001/jama.300.12.1409-b. JAMA. 2008. PMID: 18812526 No abstract available. - Effect of folic acid and B vitamins on cardiovascular disease in women.
Ntaios G, Savopoulos C, Karamitsos D. Ntaios G, et al. JAMA. 2008 Sep 24;300(12):1409; author reply 1410. doi: 10.1001/jama.300.12.1409-a. JAMA. 2008. PMID: 18812527 No abstract available. - Effect of folic acid and B vitamins on cardiovascular disease in women.
Kittisupamongkol W. Kittisupamongkol W. JAMA. 2008 Sep 24;300(12):1410; author reply 1410. doi: 10.1001/jama.300.12.1410-a. JAMA. 2008. PMID: 18812529 No abstract available.
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