Assessment of pre- and post-methionine load homocysteine for prediction of recurrent stroke and coronary artery disease in the Vitamin Intervention for Stroke Prevention Trial

Methionine (Met) loading increases total plasma homocysteine (tHcy) and assesses homocysteine metabolism. We tested the hypothesis that pre- or post-Met tHcy will predict recurrent stroke or coronary artery disease (CAD) in a subgroup analysis of the Vitamin Intervention for Stroke Prevention (VISP) trial. VISP subjects with non-disabling stroke underwent measurement of tHcy at baseline (fasting pre- and post-Met load) and were randomized to high/low-dose B-vitamin therapy for prevention of recurrent stroke or CAD. In the sample cohort of 2124 subjects, mean ± S.D. tHcy levels in μmol/l were pre-Met 13.2 ± 4.3, post-Met 30.4 ± 9.76, and pre/post-Met Δ 17.1 ± 8.3. The hazard ratio (HR) for recurrent stroke was 1.16 (p = 0.026) for 1 S.D. higher pre-Met tHcy and 1.15 (p = 0.054) for 1 S.D. higher post-Met tHcy. For CAD, the HR for 1 S.D. higher pre-Met tHcy was 1.27 (p = 0.001) and was 1.00 (p = 0.99) for post-Met tHcy. In survival analyses using pre- or post-Met as covariates, the coefficient of pre/post-Met Δ was not significant for stroke and was only marginally significant for CAD (p < 0.08), but was negative. We conclude that fasting, pre-Met tHcy is as effective as post-Met tHcy or pre/post-Met Δ in predicting the risk for stroke and CAD.