Homocysteine, B Vitamins, and the Risk of Cardiovascular Disease

Abstract

Featured Article: Clarke R, Daly L, Robinson K, Naughton E, Cahalane S, Fowler B, Graham I. Hyperhomocysteinemia: an independent risk factor for vascular disease. N Engl J Med 1991;324:1149–55.2 Our report, published in the New England Journal of Medicine in 1991, demonstrated that hyperhomocysteinemia was present in about one-third of cases with early-onset coronary heart disease, cerebral vascular disease, and peripheral vascular disease, compared with none in the age- and sex-matched controls. The results were striking and suggested that hyperhomocysteinemia was associated with at least a 3-fold excess risk of vascular disease, after adjustment for established risk factors in this population. We defined hyperhomocysteinemia on the basis of the peak homocysteine concentrations after methionine loading in 25 obligate heterozygotes (i.e., parents of children with homozygous homocystinuria), compared with 28 age- and sex-matched controls. Using assays for cystathionine β-synthase activity in a small number of cases and controls, we erroneously attributed most of the hyperhomocysteinemia to heterozygosity for cystathionine β-synthase deficiency. Nevertheless, the report attracted considerable interest because …