Effect of homocysteine-lowering treatment with folic acid plus vitamin B-6on progression of subclinical atherosclerosis: a randomised, placebo-controlled trial

Background A high plasma homocysteine concentration is associated with incr eased risk of atherothrombotic disease. We investigated the effects of homo cysteine-lowering treatment (folic acid plus vitamin B-6) on markers of sub clinical atherosclerosis among healthy siblings of patients with premature atherothrombotic disease. Methods We did a randomised, placebo-controlled trial among 158 healthy sib lings of 167 patients with premature atherothrombotic disease. 80 were assi gned placebo and 78 were assigned 5 mg folic acid and 250 mg vitamin B-6 da ily 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 ultrasonograph y, Findings Ten participants in the treatment group, and 14 in the placebo gro up dropped out. Vitamin treatment, compared with placebo,was associated wit h a decrease in fasting homocysteine concentration (from 14.7 to 7.4 mu mol /L vs from 14.7 to 12.0 mu mol/L), and in postmethionine homocysteine conce ntration (from 64.9 to 34.9 mu mol/L vs from 64.8 to 50.3 mu mol/L). It was also associated with a decreased rate of abnormal exercise electrocardiogr aphy tests (odds ratio 0.40 [0.17-0.93]; p=0.035). There was no apparent ef fect 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 Be in healthy siblings of patients with premature atherothrombotic disease is associated with a decreased occurrence of abnormal exercise electrocard iography tests, which is consistent with a decreased risk of atheroscleroti c coronary events.