Assessing the risk
Xchange newsletter - Autumn/Winter 2007/2008
Homocysteine is assayed widely in many other countries but less frequently in the UK. In this article we look at the clinical conditions associated with homocysteine in some detail.
Homocysteine is a by-product of protein metabolism and in low concentrations is not harmful to the body or blood vessels. However when excess amounts accumulate in the blood stream, arterial vessels may be damaged and the resulting inflammation can eventually cause blockage of blood flow within the circulatory system and ultimately to the heart. A number of other disease states may also arise when there are increased levels of homocysteine in the blood.
A growing body of evidence supports the use of homocysteine as a biomarker for assessing the risk of cardiovascular disease, stroke and neurodegenerative diseases.
Keeping healthy
There is a belief that lowering homocysteine levels affords a number of health benefits. According to www.homocysteine.net1, a 'safe zone' is normally considered to be below 9 µmol/L. ‘Above 14 µmol/L, you are at major risk of suffering a heart attack or stroke and the risk from Alzheimer’s disease increases by over 150%... Furthermore, patients who have had coronary angioplasty treatment [and have a homocysteine level lower than 9 µmol/L] suffer from significantly fewer new arterial blockages and cardiovascular disease later in life.’
Homocysteine is a biomarker for assessing risk of cardiovascular, stroke, and neurodegenerative diseases. Homocysteine levels are also used to assist in diagnosis and follow-up of folate and vitamin B12 deficiencies.
Some biochemistry
The amino acid homocysteine is methylated to produce methionine. This process is catalysed by methionine synthetase, which requires vitamin B12 as a co-factor. Many cases of elevated homocysteine levels can be treated by increasing the intake of vitamin B12 and folic acid.
But…
Various opinions appear in the literature regarding the use of homocysteine as a biomarker. According to Lab Tests Online2, ‘there are, as of yet, no established guidelines for homocysteine testing, and routine screening is not recommended.’ Whether it is homocysteine itself or a coincident metabolic abnormality that causes vascular disease remains, for now, an open question.
Cardiovascular disease (CVD)
Studies have been done which show that elevated blood levels of homocysteine do have a predictive value for risk of coronary artery disease similar to that of elevated cholesterol levels.3 A study by Sadeghian et al4 on premature coronary artery disease (CAD) confirmed that hyperhomocysteinemia is also an independent risk factor for premature coronary artery disease in patients below 45 years and that vitamin B12 deficiency is a preventable cause of hyperhomocysteinemia.
Birth defects
The firm association between increased homocysteine concentration and neural tube defects (NTD) has led to the hypothesis that high concentrations of homocysteine might be embryotoxic and lead to decreased foetal viability. Low concentration of vitamin B12 and transcobalamin (which delivers B12 to the cells) leads to hyperhomocysteinemia and is associated with NTD.
Dementia, Alzheimer’s and other neurodegenerative diseases
An increased plasma homocysteine level is a strong, independent risk factor for the development of dementia and Alzheimer disease.5 Recent evidence has also implicated elevated blood levels of homocysteine with neurodegenerative diseases, osteoporotic fractures and stroke. The HOPE-2 study showed that folic acid supplementation reduced the risk of stroke by 24%. In the USA and Canada, folic acid fortification of grain products was fully implemented by 1998.6
Evidence supporting the use of homocysteine testing continues to grow. For further information on this topic, contact your local Abbott representative.
The ARCHITECT Homocysteine assay, due for launch soon, is an automated chemiluminescent microparticle immunoassay (CMIA) using the CHEMIFLEX technology with high sensitivity and high throughput (200 tests/hour). A recent poster7 demonstrated the assay is a convenient, sensitive, precise method for measuring homocysteine with excellent correlation to AXSYM Homocysteine.
References:
1 www.homocysteine.net
2 www.labtestsonline.org.uk
3 Craig et al, Measurement of Total Homocysteine on the Abbott ARCHITECT Instrument (poster)
4 Sadeghian et al, Homocysteine, Vitamin B12 and Folate Levels in Premature Coronary Artery Disease. BMC Cardiovascular Disorders, 2006
5 Seshadri et al, Plasma Homocysteine as a Risk Factor for Dementia and Alzheimer's Disease. Engl J Med, 2002 346 (7)
6 Wang et al, Efficacy of Folic Acid Supplementation in Stroke Prevention: A Meta-analysis. The Lancet, 2007
7 Yoshimura et al, Evaluation of the ARCHITECT Homocysteine Assay. Poster presented at AACC Annual Meeting, 2006
