Relationship of Dietary Folate and Vitamin B6 With Coronary Heart Disease in Women—Reply

In Reply.— Drs Cleophas and van der Meulen's recommendation for a prospective trial with homocysteine-lowering therapy echoes the first such recommendation published 26 years ago.¹ A prospective controlled trial of homocysteine lowering by dietary improvement, vitamin therapy, smoking cessation, and other lifestyle improvements would add further evidence supporting the validity of the homocysteine theory of arteriosclerosis. That such a trial would meet with success is suggested by the Hordaland Homocysteine Study, which showed that plasma homocysteine levels reflect the known risk factors in the etiology of CHD.² Patients with the homozygous form of cystathionine synthase deficiency and homocystinuria are more at risk for cerebrovascular, peripheral vascular, and thrombotic vascular disease than they are for CHD. This distribution of vascular disease may reflect the more generalized and accelerated nature of the arteriosclerotic process occurring in children compared with adults with CHD. Some patients with homocystinuria survive into adulthood despite prolonged exposure to elevated homocysteine levels, but many of them develop typical generalized arteriosclerosis. Sulfhydryl-bound homocysteine within plasma proteins may not accurately reflect the atherogenic process as closely as the homocysteine bound to small, dense low-density lipoprotein aggregates.³ Unfortunately, no assay has been developed for this potentially highly atherogenic form of homocysteine.