Please select the eligibility criteria that correspond to the clinical trial below.
Title: HOPE-2 Study (Heart Outcomes Prevention Evaluation-2 Study)
Brief Summary: The purpose of the HOPE-2 study is to determine whether long term supplementation with folic acid, vitamins B6 and B12 aimed at homocyst(e)ine reduction reduces the rates of major fatal and nonfatal cardiovascular events in patients with established cardiovascular disease and/or diabetes mellitus.


Options:
A: Inclusion Criteria:

* Patients presenting within seven months of stroke (ischemic or hemorrhagic) or TIA
* Agree to take study medication
* Be geographically accessible for follow-up
* Provide written informed consent

Exclusion Criteria:

* Taking folic acid or B6 on medical advice
* Use of vitamin supplements containing folate, B6 or B12 (unless patient agrees to take study medication instead of the vitamin supplements which they usually take)
* Taking Methotrexate for any reason
* Pregnancy or women of child-bearing potential who are at risk of pregnancy
* Limited life expectancy
B: Inclusion Criteria:

Patients will be screened by their plasma homocysteine concentration. They must have a level of at least 15 mM/L to be enrolled in the study.

Patients will be excluded by any of the following criteria: age less than 21 years, expected life span less than 6 months, pregnancy, metastatic cancer, end-stage liver disease, treatment with methotrexate, other anti-folate medication or anticonvulsants, unreliable or likely noncompliant, participation in another long-term trial, or unwilling or unable to give informed consent.

Exclusion Criteria:
C: Inclusion Criteria:chronic

* kidney disease (clearence between 15-70ml/min)

Exclusion Criteria:

* diabetes mellitus (ADA criteria), active vasculitis, nephrotic syndrome (\>3g protein/24h urine), renal transplantation, fasting total cholesterol \> 7 mmol/L, cholesterol-lowering therapy within three months prior to inclusion or known ischaemic coronary, cerebrovascular or peripheral arterial disease
D: 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.

Answer: D