Homocysteine and Atherosclerosis
(July 2002)
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Homocysteine and Atherosclerosis.pdf)
What is it?
Homocysteine is sulphur - containing amino acid, an intermediate of methionine metabolism (an essential amino acid found in meat and dairy products) which is now known to be a significant independent risk factor for Coronary Artery Disease.
The normal Homocysteine level in plasma: 4 - 12 µmol/L
What is the clinical significance of Homocysteine?
Homocysteine
- is an independent vascular disease risk factor.
- is synergistic with smoking + hypertension as risk factors.
- is additive with hyperlipidaemia.
In 1995 Boushey et al performed a meta-analysis of 27 studies correlating homocysteine to vascular disease. They concluded that even mildly raised plasma total Homocysteine contributes to ~ 10% of total population Coronary Artery disease risk and that raised homocysteine is a risk factor for CVA's (greater than Peripheral Vascular Disease).
How does Homocysteine cause atherosclerosis?
The current idea is that high blood Homocysteine interacts with Low Density Lipoprotein enhancing lipoprotein oxidation, stimulates endothelial smooth muscle growth which enhances the growth of the atherosclerotic plaque and induces alterations in endothelial function which alters nitric oxide release from the endothelium.
What causes raised Homocysteine levels?
Dietary problems - the most common cause
- Too high methionine intake from dietary protein
- Low levels of vitamins B6, B12 and Folate
- Highly refined foods in the modern Australian diet such as bread rice and pasta, are markedly depleted in the B group vitamins, phytochemical (natural plant-derived) anti-oxidants and fat - soluble vitamins.
- Folate is the most important vitamin - it is a vital cofactor in the 'remethylation pathway' the primary pathway by which the body regulates homocysteine levels.
- Zinc deficiency (theoretically)
Toxins (common)
Cigarette smoking
Heavy alcohol intake |
Genetic defects (uncommon)
Remethylation pathway (commonest gene)
Transsulfuration pathway (rare) |
Diseases
Renal failure
Hypothyroidism
Malignancy (leukaemia)
Psoriasis
Alcoholism |
Drugs
Methotrexate
Nitrous Oxide
Isoniazid
Anticonvulsants |
Do homocysteine levels change with age?
Yes. Homocysteine increases with age and in women rises after the menopause. Incidentally, levels are on average 50% less in pregnancy.
Can HAPS measure Homocysteine?
Yes. Always check that the patient is not folate deficient first.
Collection Information
| Specimen |
10mL venous blood in EDTA tube. The specimen should be kept on ice if there will be a delay before delivery to the laboratory. |
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| Preparation |
The patient should be fasted for 10-12 hours. Water can be drunk but no other beverages. |
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What are the indications for measuring plasma homocysteine?
Family History of arteriovascular disease
- Signs/symptoms/history of premature vascular disease (< 60 years)
What is a Methionine loading test?
Oral Methionine loading tests give the most accurate results - between 27 to 40% of the population will have normal fasting Homocysteine levels that are only raised after an oral methionine loading test.
Methionine Loading Test
| Principle |
Many patients with raised Homocysteine have poor long-term clearance of homocysteine, so supplying the homocysteine precursor methionine (proximal to the metabolic block) results in a marked rise in venous homocysteine in affected individuals. |
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| Contraindications |
Creatinine > 0.130 mmol/L. Patients with renal impairment are unable to effectively filter protein loads. |
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| Procedure |
- Patient should be fasted for 10 - 12 hours prior to the test. There should be no smoking during the procedure.
- The patient is given 100 mg/kg body weight oral dose of L-Methionine.
- Blood is measured at time 0 and 4 hours after the Methionine dose.
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| Interpretation |
In normal individuals there is only a minor change in homocysteine during the test. Hyperhomocysteinaemic patients classically show a doubling of the homocysteine level, usually to a 4 hour peak > 22 µmol/L. |
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What are the indications for a Methionine loading test?
Normal previous plasma Homocysteine level in individual suffering from or with strong family history of premature vascular disease (< 60 yrs age).
About the Author
This HAPS Communique was written by Dr Phil Tynan , Former Director of Clinical Chemistry.
Clinical Chemistry Contacts
Dr Huy Tran - Director - 49214005
Professor Geoffrey Kellerman - 49214000
Clinical Chemistry Laboratory - 49214405