Homocysteine in the prevention of ischemic heart disease, stroke and venous thromboembolism: therapeutic target or just another distraction?
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PURPOSE OF REVIEW: Homocysteine has been proposed as a potentially modifiable risk factor for arterial and venous vascular disease. This notion is supported by a large body of literature derived from observations in patients with rare inborn errors of metabolism associated with homocystinuria, experimental studies, which show that homocysteine promotes atherogenesis and thrombosis and epidemiological studies, which in general suggest a graded and independent relationship between homocysteine and atherothrombotic vascular risk. RECENT FINDINGS: The current review briefly summarizes observational studies with emphasis on new meta-analyses linking homocysteine to ischemic heart disease, stroke, and venous thromboembolism. These data support weak associations between homocysteine and vascular risk. A number of recent large randomized controlled trials failed to demonstrate benefit for homocysteine lowering with B vitamin supplements in the prevention of cardiovascular events and venous thrombosis. These studies, however, may have been insufficiently powered to detect modest but clinically important treatment benefits. Therefore, completion of ongoing large randomized trials is essential. SUMMARY: At present, the status of homocysteine as a target for intervention in the prevention of atherothrombotic arterial and venous disease is uncertain. Current evidence does not support the use of B vitamin supplements to reduce vascular risk. Ongoing large randomized trials will provide further clarity on this subject.
