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16th World Congress on Heart Disease

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Folic Acid and B Vitamins Do Not Reduce the Risk of Major Cardiovascular Events in Patients With Vascular Disease

April 13, 2006

By: Jennifer Tartaglia MS and Asher Kimchi M.D.

Ontario, Canada – Observational studies suggest that mild to moderate elevations in homocysteine levels may increase cardiovascular disease. Folic acid, vitamin B12, and vitamin B6 lower plasma homocysteine levels. The Heart Outcomes Prevention Evaluation (HOPE) 2 study investigated whether supplementation with folic acid and vitamins B12 and B6 reduce the risk of major cardiovascular events in high risk patients. The trial found that daily administration of folic acid and vitamins B6 and B12 lowered homocysteine levels but did not reduce the incidence of major cardiovascular events. These results were published in the April 13, 2006 issue of the New England Journal of Medicine.

The study was a randomized, double blind, placebo-controlled trial. It enrolled 5522 patients over the age of 55 who had a history of vascular disease or diabetes and other risk factors for atherosclerosis. These participants were randomly assigned to receive daily administration of a combination of 2.5mg folic acid, 50mg vitamin B6, and 1mg vitamin B12 or matching placebo. Patients were followed for an average of 5 years.

The investigators found that the change from baseline in homocysteine levels between the 2 treatment groups was 0.4mg per liter at two years and at the end of the study. The primary study finding was that 519 patients (18.8%) in the active-treatment group died of cardiovascular causes or had a myocardial infarction (MI) or stroke (primary outcome events), which was not significantly different from the 547 patients (19.8%) in the placebo group (Relative Risk, 0.95; 95% Confidence Interval, 0.84 to 1.07; P = 0.41). In addition, there were no significant differences between treatment groups in any secondary outcomes.

The authors propose that the disparity between the epidemiology of homocysteine and the results of clinical trials may be partly due to homocysteine’s relationship to renal dysfunction, smoking, increased blood pressure, and other cardiovascular risk factors such as atherosclerosis. This relationship helps to explain why homocysteine levels may be a good marker, but not a direct cause, of vascular disease.

The findings presented in this study suggest that folic acid and B vitamin supplements, while having an observable effect on homocysteine levels, have no beneficial effect as a preventative treatment for major vascular events in high-risk patients.

Authors (The Writing Group): Eva Lonn, M.D., Salim Yusuf, D.Phil., M.B., B.S., Malcolm J. Arnold, M.D., Patrick Sheridan, M.Sc., Janice Pogue, M.Sc., Mary Micks, C.T.R.C., Matthew J. McQueen, M.D., Ph.D., Jeffrey Probstfield, M.D., George Fodor, M.D., Ph.D., Claes Held, M.D., Ph.D., and Jacques Genest, Jr., M.D.


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