Homocysteine

Aka: Homocysteine, Hyperhomocysteinemia

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II. Epidemiology

  1. Elevated in 15-30% of patients with premature CAD

III. Pathophysiology

  1. Folate needed to convert Homocysteine to Methionine
  2. Initially thought that lowering Homocysteine levels decreased Cardiovascular Risk
    1. Dose response curve: lowest Folate, Highest risk
  3. Now Folate supplementation not thought to impact Cardiovascular Risk

IV. Causes: Hyperhomocysteinemia

  1. Vitamin Deficiency
    1. Folate Deficiency
    2. Vitamin B6 Deficiency
    3. Vitamin B12 Deficiency
  2. Chronic Disease
    1. Chronic Renal Failure
    2. Hypothyroidism
    3. Psoriasis
    4. Cancer
    5. Tobacco Abuse
  3. Medications
    1. Anticonvulsants
    2. Methotrexate
    3. Nitrous Oxide
  4. Homocystinuria (Inherited)

V. Complications: High Homocysteine levels

  1. Coronary Artery Disease
  2. Cerebrovascular Accident
  3. Peripheral Vascular Disease
  4. Deep venous thrombosis
  5. Hypertension
  6. Dementia may also be related

VI. Labs: Protocol for Blood Total Homocysteine concentrations

  1. Step 1: Collect
    1. Draw in tube with Anticoagulant
    2. EDTA, Heparin, or Sodium Citrate
  2. Step 2: Process
    1. Spin sample within 30 minutes of collection
    2. Otherwise risk of false elevation from RBCs
  3. Step 3: Storage
    1. Refrigerate up to 2-3 weeks OR
    2. Frozen for 2-3 months

VII. Labs: Homocysteine Level Interpretation

  1. Optimal Homocysteine: <12 umol/L
  2. Borderline Homocysteine: 12-15 umol/L
  3. Hyperhomocysteinemia: >15 umol/L

VIII. Management

  1. Homocysteine lowering therapy lowers CAD risk
    1. See Cardiac Risk Management
  2. Measures to lower Homocysteine levels
    1. Folic Acid supplementation
    2. Vitamin B12 Supplementation
    3. Vitamin B6 supplementation
    4. References
      1. Schnyder (2002) JAMA 288:973-9 [PubMed]
      2. Rimm (1998) JAMA 279:359-64 [PubMed]

IX. Management: Folate Dosing Protocol

  1. High risk patient with Homocysteine >12 umol/L
    1. Multivitamin (with 400 ug Folate) qd AND
    2. Folic Acid 800 ug qd
  2. Recheck Homocysteine Level in 8 weeks: Normal
    1. Continue Multivitamin
    2. Discontinue Folic Acid
    3. Recheck Homocysteine again in 8 weeks
  3. Recheck Homocysteine Level in 8 weeks: >12 umol/L
    1. Continue Multivitamin
    2. Increase Folic Acid to 2 mg qd for 8 weeks
      1. Folic Acid is Safe <5mg/day
    3. Recheck Homocysteine again in 8 weeks
      1. If normal
        1. Continue Multivitamin
        2. Discontinue Folate
      2. If still increased
        1. Check Vitamin B6 Level
        2. Increase Folate to 5 mg/day
        3. Assess patient compliance
        4. Test for other causes

X. References

  1. Fallest-Strobl (1997) Am Fam Physician 56(6):1612 [PubMed]
  2. Morrison (1996) JAMA 275: 1893-6 [PubMed]

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