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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2002;22:1051.)
© 2002 American Heart Association, Inc.

Letters to the Editor

Validation of Homocyst(e)ine-Lowering Treatment in the Era of Folic Acid Fortification of Cereal Grains

M. Rene’ Malinow

Oregon Regional Primate Research Center, Beaverton, Ore

James F. Toole

Wake Forest University School of Medicine, Winston-Salem, NC

To the Editor:

Bostom et al¹ assert that fortification of grain products with folic acid in the United States will negate ongoing clinical trials on US populations. However, by dismissing the general population, he overlooks the fact that it is still beneficial to focus on those with elevated homocyst(e)ine [H(e)] levels. [Plasma or serum H(e), or total homocysteine, refers to the sum of the concentrations of the sulfhydryl amino acid homocysteine and the homocysteinyl moieties of the disulfides homocystine and homocysteine-cysteine, whether free or bound to plasma proteins.] Lowering response of H(e) to folic acid supplementation is related to basal concentrations of H(e).²

Extrapolating from study by Bostom et al¹, to indicate that studies such as the Vitamin Intervention for Stroke Prevention (VISP) Study³ would not remain adequately powered to test the H(e) lowering hypothesis, is incorrect because the study population in the article by Bostom et al differed substantially from that of VISP. VISP does not use the "general population," yet rather those with a previous stroke and who were above a fixed level of H(e) at baseline³ above the 25th percentile. Thus, a shift in the general population values for H(e) would be more likely to reduce the prevalence of eligible subjects (ie, increase the difficulty of recruitment), yet would have a smaller effect on the average level of H(e) at admission, because all individuals were above a fixed threshold at admission.³ This selection would generate a population where it could reasonably be expected to observe a significant decrease in . . . [Full Text of this Article]

Andrew G. Bostom

Rhode Island Hospital, Division of Renal Disease, Providence, RI