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

V. Complications: High Homocysteine levels

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

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Ontology: Hyperhomocysteinemia (C0598608)

Definition (MSH) Condition in which the plasma levels of homocysteine and related metabolites are elevated (>13.9 μmol/l). Hyperhomocysteinemia can be familial or acquired. Development of the acquired hyperhomocysteinemia is mostly associated with vitamins B and/or folate deficiency (e.g., PERNICIOUS ANEMIA, vitamin malabsorption). Familial hyperhomocysteinemia often results in a more severe elevation of total homocysteine and excretion into the urine, resulting in HOMOCYSTINURIA. Hyperhomocysteinemia is a risk factor for cardiovascular and neurodegenerative diseases, osteoporotic fractures and complications during pregnancy.
Definition (NCI) A serious metabolic condition caused by mutations in the MTHFR gene, medications, or nutritional deficiency. It results in increased levels of homocysteine in the blood. Patients with this condition are at an increased risk for recurrent blood clots formation and cardiovascular accidents.
Concepts Disease or Syndrome (T047)
MSH D020138
SnomedCT 419503008
Spanish hiperhomocisteinemia (trastorno), hiperhomocisteinemia, Hiperhomocistienemia, Hiperhomocisteinemia
Japanese 高ホモシステイン血症, コウホモシステインケッショウ, コウホモシステインケツショウ
Swedish Hyperhomocysteinemi
Czech hyperhomocysteinémie, Hyperhomocysteinemie
Finnish Hyperhomokysteinemia
English Hyperhomocysteinemias, Hyperhomocysteinemia [Disease/Finding], hyperhomocysteinaemia, hyperhomocysteinemia, Hyperhomocysteinaemia, Hyperhomocysteinemia, Hyperhomocysteinemia (disorder)
Portuguese Hiper-Homocisteinemia, Hiperhomocisteinemia, Hiper-homocisteinemia
Polish Hiperhomocysteinemia
Hungarian Hyperhomocysteinaemia
Norwegian Hyperhomocysteinemi
Dutch hyperhomocysteïnemie, Homocysteïnemie, hyper-, Hyperhomocysteïnemie
German Hyperhomocysteinaemie, Hyperhomozystinämie
French Hyperhomocystéinémie
Italian Iperomocisteinemia

Ontology: Homocysteine cysteine disulfide:SCnc:Pt:Ser/Plas:Qn (C1315089)

Concepts Clinical Attribute (T201)
LNC 32615-7
English Homocysteine cysteine disulfide [Moles/volume] in Serum or Plasma, Hycs-Cys diS SerPl-sCnc, Homocysteine cysteine disulfide:SCnc:Pt:Ser/Plas:Qn, Homocysteine cysteine disulfide:Substance Concentration:Point in time:Serum/Plasma:Quantitative