Inclusion Criteria- Women and men 55 years of age or over with established CVD and at high risk for future fatal and nonfatal CV events, defined as:
1. Documented coronary artery disease (CAD);
2. Documented peripheral vascular disease (PVD);
3. Documented cerebrovascular disease;
4. Diabetes with one of the following; additional cardiovascular risk factors:
i) hypertension (BP >160 mmHg systolic or >90 mmHg diastolic or on treatment); ii) total cholesterol >5.2 mmol/L (>200 mg/dl); iii) HDL cholesterol <0.9 mmol/L (3.5 mg/dl); iv) current cigarette smoker; v) any evidence of previous vascular disease
- Provision of informed consent
Exclusion Criteria- Current use of any vitamin supplements containing folic acid >200 micrograms/day. The patients taking such vitamin supplements can be asked if they agree to discontinue these supplements. If they agree, they can be randomized to the study following a one month wash-out period.
- Known previous adverse reactions to folic acid and/or vitamin B6 and/or B12.
- Planned cardiac, peripheral or cerebrovascular revascularization, defined as a decision taken by the patient and his or her physician(s) to perform surgical or percutaneous transluminal revascularization within the next 6 months.
- Hemodynamically significant primary valvular outflow tract obstruction (e.g. mitral stenosis, asymmetric septal hypertrophy, malfunctioning prosthetic valve).
- Constrictive pericarditis.
- Complex congenital heart disease.
- Syncopal episodes presumed to be due to uncontrolled life-threatening arrhythmias (asymptomatic arrhythmias including ventricular tachycardia are not exclusion criteria.
- Uncontrolled hypertension.
- Cor pulmonale.
- Heart transplant recipient.
- Other important non-cardiovascular disease(s) expected to limit compliance and/or impact on patient's ability to complete the study, such as: *history of alcohol or drug abuse, *psychiatric disorders, *senility, *severe physical disability, *illnesses including terminal stage of cancer and other major systemic illnesses expected to limit the patient's ability to comply with the study protocol and to complete the study.