Clinical relevance of hyperhomocysteinaemia in atherothrombotic disease

High fasting plasma homocysteine levels (>12 to 15 mu mol/L) are commonly e ncountered in clinical practice and are associated with increased risk of a therothrombotic disease. Treatment with folic acid (1 to 5 mg/day) is inexp ensive and effective in normalising plasma homocysteine levels. High plasma homocysteine levels after methionine loading (>40 to 50 mu mol/L) are also common and can be treated with pyridoxine-based regimens (50 to 250 mg/day ). As compared with fasting plasma homocysteine levels, the association bet ween high post-methionine loading plasma homocysteine levels and atherothro mbotic disease has been less extensively studied. There is reasonable, but not clearly definitive, evidence that high plasma homocysteine levels are c ausally related to atherothrombotic disease. Results of randomised trials o f homocysteine-lowering treatment with clinical end-points will be availabl e in 4 to 6 years. At present, a reasonable policy for the practising clini cian would be to consider homocysteine-lowering treatment in individuals at very high risk of atherothrombotic disease, such as patients with clinical ly manifest atherothrombotic disease with onset before 55 years of age, pat ients with end stage renal disease, and healthy subjects with a strong fami ly history of early-onset atherothrombotic disease. Such a policy should be reassessed as the results of randomised trials become available.