Hyperhomocysteinemia: could the post-methionine oral loading test sometimes be avoided?

Background and Objectives. Measurement of homocysteinemia, a risk factor for venous and arterial thrombosis, is carried out in patients fasting for 12 hours and after an oral methionine load (PML). The procedure is time-consuming and several of the patients suffer from nausea and malaise. We wondered whether methionine loading could sometimes be avoided by considering fasting homocysteinemia (tHcy) levels. Design and Methods. We evaluated whether fasting tHcy levels were useful to predict PML and ΔPML tHcy with acceptable sensitivity and specificity in 381 patients with venous and arterial thrombosis through the generation of receiver operating characteristic curves. Results. Both PML and ΔPML tHcy correlated with fasting tHcy values. The cut-off of fasting tHcy value yielding a 100% sensitivity in predicting normal PML and ΔPML tHcy was 6.5 and 5.0 μmol/L in females, and 7.1 and 7.2 μmol/L in males. Fasting tHcy values yielding a 95% specificity in predicting a positive PML and tHcy result ranged from 12.5 to 13.1 μmol/L in males and from 10.4 to 10.5 μmol/L in females. A 95% specificity in predicting a positive ΔPML tHcy result ranged from 10.8 to 11.6 μmol/L in females and from 15.9 to 17.0 μmol/L in men. Considering PML tHcy, 186 out of 381 patients could have avoided methionine loading while using ΔPML tHcy 123 out of 381 could have done so. Interpretation and Conclusions. Nearly 50% of our patients considering PML tHcy, and about 30% considering δPML tHcy could have been spared the methionine loading test. We propose this model for those who wish to carry out this analysis on their own.