Homocyst(e)ine and Stroke

ABSTRACT

Homocyst(e)ine elevation is associated with a two- to threefold fold increased risk of ischemic stroke. Although most commonly associated with large-artery atherosclerosis and venous thrombosis, hyperhomocysteinemia may contribute to stroke by other mechanisms as well. Levels of homocysteine are determined by genetic regulation of the enzymes involved in homocyst(e)ine metabolism and by levels of the vitamin cofactors (folate, B₆, and B₁₂) associated with those reactions. Emerging evidence suggests that genetic variation within this pathway, such as the methyleneterahydrofolate reductase and cystathionine β-synthase and nicotinamide N-methyltransferase genes, increases the risk of ischemic stroke. The introduction of grain folate fortification in 1998 has reduced homocyst(e)ine concentrations in the U.S. population. However, it is important to screen for vitamin B₁₂ deficiency and be cognizant that vitamin B₆ levels may be low in the elderly and in individuals with inflammatory disorders. The Vitamin Intervention in Stroke Prevention study failed to prove that high-dose supplementation with folate, B₆, and B₁₂ reduced the risk of recurrent stroke or myocardial infarction at 2 years; however, there is an ongoing clinical trial evaluating the potential benefit of vitamin supplementation.

KEYWORDS

Homocysteine - folate - vitamins - genetics

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