To assess the risk for homocyst(e)ine-associated vascular disease, ove
rt hyperhomocyst(e)inemia should be demonstrated. In nonhomocystinuric
subjects, clinical vascular disease must have developed after 40 or m
ore years of persistent hyperhomocyst(e)inemia which may not be presen
t without a genetic defect(s). Nongenetic factors, however, may amplif
y or mask phenotypic expression of a genetic defect, causing difficult
ies for the evaluation of hyperhomocyst(e)inemia based on plasma homoc
yst(e)ine concentration alone. Therefore, the search for genetic defec
ts seems as important as the determination of plasma homocyst(e)ine co
ncentration in evaluating the relationship between hyperhomocyst(e)ine
mia and the development of vascular disease. If genetic defect, such a
s heterozygous cystathionine synthase deficiency or thermolabile methy
lenetetrahydrofolate reductase is not detected, post-methionine homocy
st(e)ine determination is a suitable means to identify genetic suscept
ibility to hyperhomocyst(e)inemia when the environmental factors are s
imilar in the control and study groups.