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An Introduction to the Role of Homocysteine in Cardiovascular Disease

Cardiovascular disease encompassing diseases involving the heart or blood vessel is currently the leading cause of death in Australian adults. It is primarily caused by a process called atherosclerosis. This refers to the build up of cholesterol (a type of fat) within the walls of important blood vessels throughout the body. Plaques consisting of fat cells, cell debris and scar tissue, attach to the inside of artery walls and obstruct the flow of blood. Sometimes the plaques can rupture or have clots form on top of them which further obstruct blood flow. When this occurs in the vessels supplying the heart (coronary arteries) a heart attack may occur. In this case, part of the heart muscle dies because it is not getting enough blood and oxygen supply. Extensive research has been conducted into the underlying causes and risk factors for cardiovascular disease. Once these agents have been identified, strategies can be implemented in order to prevent morbidity and mortality from cardiovascular disease. Of particular interest is the role of homocysteine in the development of cardiovascular disease.

What is Homocysteine?

Homocysteine is one of many amino acid molecules found in the bloodstream. Amino acids are small compounds which form the building blocks for proteins in the body. Studies have shown that increased levels of homocysteine are associated with an increased risk of heart attack and stroke. People with inherited high levels of homocysteine also develop earlier vascular disease (affecting the blood vessels). The theory behind this relationship is that homocysteine causes damage to the lining of blood vessels, which increases their likelihood for clot formation. The exact role of homocysteine however is unknown. The molecule may just be an indicator of cardiovascular disease rather than actually causing the disease.

Reducing Homocysteine Levels

Current research has shown that folic acid and vitamin B12 supplements reduce homocysteine blood levels by a quarter. It was thought that lowering levels of homocysteine with vitamins would therefore reduce cardiovascular events such as heart attack and stroke. However a big evaluation of all studies to date did not show a significant reduction in the risk of cardiovascular disease, coronary heart disease, stroke or death. Therefore homocysteine may not be a cause of atherosclerosis but rise secondarily when cardiovascular disease or risk factors are present. So far, studies have not really confirmed its role. Furthermore vitamin B12 is associated with its own risks of adverse events so you should be careful taking it without a good purpose.

Future Research on Homocysteine

Large trials of homocysteine are still ongoing. Hopefully this research will be better able to answer whether lowering homocysteine levels with B-vitamin supplementation will lower your risk of cardiovascular disease. Until this research is available B-vitamin supplements are not recommended for patients at risk of cardiovascular disease as the risks may exceed the benefits. (Article kindly written by Dr Kathleen Potter B.Med.Sci MBChB, Cardiology Department Royal Perth Hospital, Editorial Advisory Board Member for Virtual Cardiac Centre)

References

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  7. Homocysteine Studies Collaboration. Homocysteine and risk of ischemic heart disease and stroke: a meta-analysis. JAMA. 2002;288:2015-22.
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  10. Lonn E, Yusuf S, Arnold MJ, et al. Homocysteine lowering with folic acid and B vitamins in vascular disease. N Engl J Med. 2006;354:1567-77.
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  12. Toole JF, Malinow MR, Chambless LE, et al. Lowering homocysteine in patients with ischemic stroke to prevent recurrent stroke, myocardial infarction, and death: the Vitamin Intervention for Stroke Prevention (VISP) randomized controlled trial. JAMA. 2004;291:565-75.
  13. Bazzano LA, Reynolds K, Holder KN, He J. Effect of folic acid supplementation on risk of cardiovascular diseases: a meta-analysis of randomized controlled trials. JAMA. 2006;296:2720-6.
  14. The VITATOPS Trial Study Group. The VITATOPS (Vitamins to Prevent Stroke) Trial: rationale and design of an international, large, simple, randomised trial of homocysteine-lowering multivitamin therapy in patients with recent transient ischaemic attack or stroke. Cerebrovasc Dis. 2002;13:120-6.
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