Effect of homocysteine-lowering treatment with folic acid plus vitamin B6 on progression of subclinical atherosclerosis: a randomised, placebo-controlled trial Original Research Article

Background A high plasma homocysteine concentration is associated with increased risk of atherothrombotic disease. We investigated the effects of homocysteine-lowering treatment (folic acid plus vitamin B6) on markers of subclinical atherosclerosis among healthy siblings of patients with premature atherothrombotic disease. Methods We did a randomised, placebo-controlled trial among 158 healthy siblings of 167 patients with premature atherothrombotic disease. 80 were assigned placebo and 78 were assigned 5 mg folic acid and 250 mg vitamin B6 daily for 2 years. The primary endpoint was the development or progression of subclinical atherosclerosis as estimated from exercise electrocardiography, the ankle-brachial pressure index, and carotid and femoral ultrasonography. Findings Ten participants in the treatment group, and 14 in the placebo group dropped out. Vitamin treatment, compared with placebo, was associated with a decrease in fasting homocysteine concentration (from 14·7 to 7·4 μmol/L vs from 14·7 to 12·0 μmol/L), and in postmethionine homocysteine concentration (from 64·9 to 34·9 μmol/L vs from 64·8 to 50·3 μmol/L). It was also associated with a decreased rate of abnormal exercise electrocardiography tests (odds ratio 0·40 [0·17–0·93]; p=0·035). There was no apparent effect of vitamin treatment on ankle-brachial pressure indices (0·87 [0·56–1·33]), or on carotid and peripheral-arterial outcome variables (1·02 [0·26–4·05] and 0·86 [0·47–1·59], respectively). Interpretation Homocysteine-lowering treatment with folic acid plus vitamin B6 in healthy siblings of patients with premature atherothrombotic disease is associated with a decreased occurrence of abnormal exercise electrocardiography tests, which is consistent with a decreased risk of atherosclerotic coronary events.