The HART study is designed as a substudy of the Heart Outcomes Prevention Evaluation-2 (HOPE-2)trial which evaluates the effect of combined therapy ? folic acid and vitamin B6 and B12 on clinical events. The study is designed to enrol 900 study participants randomized to homocysteine lowering therapies or placebo. Follow-up will estimate over 5 years. Study participants will undergo yearly carotid B-Mode ultrasound examinations.