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EPIDEMIOLOGICAL ASSESSMENT OF HOMOCYSTEINAEMIA AS A RISK FACTOR FOR VASCULAR DISEASE

Objective

1 To standardize diagnostic techniques for the detection of hyperhomocysteinaemia.
2 To establish the prevalence of hyperhomocysteinaemia in subjects with vascular disease compared with normal subjects in different European countries.
3 To study possible interactions between hyperhomocysteinaemia and conventional risk factors for vascular disease.
4 To establish a data base of pooled results from existing studies or hyperhomocysteinaemia and vascular disease.
5 To initiate a simple long-term follow-up study of obligate heterozygotes for homocysteinaemia to ascertain whether such subjects develop premature vascular disease.
Recently it has been suggested that a raised level of the amino acid homocysteine in the blood (hyperhomocysteinaemia) may be a new and independent risk factor for vascular disease in over 20 studies to date.

Homocysteine is a sulphur amino acid produced by the demethylation of methionine. Its concentration in blood is determined by genetic and nutritional influences. Raised homocysteine levels (hyperhomocysteinaemia) may therefore result from inherited enzyme deficiencies or from insufficient intake of certain vitamins.

Methods for the diagnosis of hyperhomocysteinaemia involving a methionine loading test have been successfully developed, standardized and applied.

A multicentre European case control study of hyperhomocysteinaemia and vascular disease has been designed and completed successfully. This is the largest case control study to date and the only one with complete, predefined methods uniformly applied to multiple centres in different countries. Preliminary analysis indicates that earlier observations relating hyperhomocysteinaemia to vascular disease have been confirmed. The study has sufficient power to elucidate relationships with conventional risk factors and with nutritional determinants of homocysteine levels, including folic acid, vitamin B12 and vitamin B6. It has the potential to suggest innovative new possibilities for cardiovascular disease prevention and treatment.

Existing data relating hyperhomocysteinaemia to vascular disease have been examined and analysed. Case control and more recent prospective data confirm a strong and consistent relationship between hyperhomocysteinaemia and vascular disease. This relationship may be casual.
Conventional risk factors such as hyperlipidaemia, cigarette smoking and hypertension do not fully explain the mass occurrence of atherosclerotic vascular disease in developed societies. Recently it has been suggested that a raised level of the amino acid homocysteine in the blood (hyperhomocysteinaemia) may be a 'new' and independent risk factor for vascular disease. Hyperhomocysteinaemia has been noted to be associated with vascular disease in over 20 studies to date. The relationship may be causal.
Homocysteine is a sulphur amino acid produced by the demethylation of methionine. Its concentration in blood is determined by genetic and nutritional influences. Raised homocysteine levels (hyperhomocysteinaemia) may therefore result from inherited enzyme deficiencies or from insufficient intake of certain vitamins, notably folic acid and vitamin B12.

Coordinator

Adelaide Hospital
Address
Peter Street
Dublin 8
Ireland