In Reply: Dr Rossi and colleagues, Dr Ntaios and colleagues, and Dr Scholl make the important point that the lack of proven benefit from homocysteine-lowering treatment by folic acid and vitamin B12 in the WENBIT study could be attributed to the fact that most of the 3090 participants had normal plasma levels of total homocysteine at baseline.
At the time the WENBIT study was designed, data from a prospective study of 587 patients from Western Norway with angiographically confirmed CAD demonstrated a strong and graded relationship between plasma total homocysteine levels at baseline and overall mortality after a median follow-up of 4.6 years.1 Using plasma concentrations of less than 9 μmol/L as reference, mortality ratios adjusted for multiple risk factors were 1.9 for patients with plasma concentrations of 9.0 to 14.9 μmol/L.1 These and similar results from other observational studies during the 1990s suggested a dose-response relationship across the entire range of homocysteine concentrations. This contention was supported by our observation that baseline level of total homocysteine in plasma was a significant predictor of the primary end point in the WENBIT study.
Lowering Homocysteine With B Vitamins in Patients With Coronary Artery Disease—Reply. JAMA. 2008;300(24):2852-2854. doi:10.1001/jama.2008.838