To the Editor: Despite the negative outcomes of the Women's Antioxidant and Folic Acid Cardiovascular Study (WAFACS) by Dr Albert and colleagues1 and the VISP, HOPE-2, NORVIT, CHAOS-2, and WENBIT trials,2 we believe that the homocysteine hypothesis is by no means dead. Although pharmacological intervention with B vitamin supplementation does not seem to provide beneficial cardiovascular outcomes, nutritional intervention with fortification of cereal grains with folic acid may have a significant long-term effect on primary cardiovascular prevention.
Hyperhomocysteinemia does not appear to be as important as other cardiovascular risk factors, such as smoking, dyslipidemia, diabetes mellitus, and hypertension, associated with only a small share of the atherosclerotic process.3 Hence, administration of homocysteine-lowering B vitamin supplements to modify this minor risk factor may require a long period to demonstrate clinical benefits—probably longer than 7.3 years, which was the follow-up duration of the WAFACS trial.1 Adding 1 more pill to a treatment regimen for such a long period for such a delayed result may not be worthwhile.
On the other hand, fortification of grain products with folic acid exerts a continuous, anti-atherogenic effect that, although modest, would be expected to cumulate over years, possibly leading to a significant long-term reduction in cardiovascular events. Therefore, the ultimate challenge for the homocysteine hypothesis will not necessarily be the ongoing large randomized trials or the preplanned meta-analysis of the B-Vitamin Treatment Trialist's Collaboration.4 The verdict will be reached with the assessment of the long-term effect of folic acid fortification on cardiovascular risk. Such effects may be observable soon, since fortification in the United States and Canada is already 10 years old.5
Financial Disclosures: None reported.
Country-Specific Mortality and Growth Failure in Infancy and Yound Children and Association With Material Stature
Use interactive graphics and maps to view and sort country-specific infant and early dhildhood mortality and growth failure data and their association with maternal
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