JUDGING BY the number of citations in the medical literature, the lay press, and the Internet, homocysteine is the favorite amino acid of the late 1990s. This is primarily because of the recognition during the past several years that hyperhomocysteinemia is an important risk factor for vascular disease, independent of long-recognized factors such as hyperlipidemia, hypertension, and smoking. A wealth of epidemiological data has accumulated in support of the hypothesis initially advanced by Kilmer McCully in 1969,1 which was based on autopsy findings from 2 children with elevated plasma homocysteine levels. By now, more than 20 case-control and cross-sectional studies, involving more than 15000 patients, have validated this correlation.2 A recent meta-analysis by Boushey et al3 estimated that 10% of the risk of coronary artery disease in the general population is due to homocysteine.3 Of particular importance to neurologists is the increased prevalence of cerebrovascular disease in patients whose homocysteine concentrations were in the upper quartile.4 What is not yet clear is whether intervention to lower plasma homocysteine levels is effective in decreasing the risk of vascular disease, although well-designed multicenter trials are under way to answer this important question.
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