Hyperhomocysteinaemia as a cardiovascular risk factor: an update.
There is overwhelming epidemiological evidence that hyperhomocysteinaemia is an independent and graded cardiovascular risk factor, although a cause-and-effect relationship is still unproven. Acquired causes of hyperhomocysteinaemia include B-vitamin deficiencies and renal insufficiency. The most important inherited cause is a point mutation in methylenetetrahydrofolate reductase gene, which is, remarkably, not associated with an increased cardiovascular risk. A methionine loading test identifies substantially more subjects with hyperhomocysteinaemia compared with a fasting homocysteine determination alone. Repeated blood sampling is necessary due to an intra-individual variability in homocysteine concentrations up to 25%. A conservative reference value for fasting homocysteine is 15 micromol/l, although there seems to be no definite threshold in the presumed linear relation between homocysteine concentration and cardiovascular risk. The pathophysiological mechanism of homocysteine-induced cardiovascular disease is still not elucidated. The concept of endothelial dysfunction, demonstrated by impaired endothelium-dependent vasodilation, by oxidant damage has been confirmed in hyperhomocysteinaemic healthy adults. Folic acid supplementation (0.5 mg daily) can be considered the optimum homocysteine lowering therapy, with the exception of renal failure patients. Ongoing large prospective, randomised controlled clinical trials are investigating the potential beneficial effect of homocysteine lowering therapy on cardiovascular morbidity and mortality in subjects with hyperhomocysteinaemia.
van der Griend
R
R
Department of Internal Medicine, Sint Antonius Hospital, Nieuwegein, The Netherlands. r.griend@digd.azu.nl
Biesma
D H
DH
Banga
J D
JD
D000328:Adult; D002318:Cardiovascular Diseases / Q000150:complications / Q000453:epidemiology*; D006710:Homocysteine / Q000378:metabolism; D006801:Humans; D020138:Hyperhomocysteinemia / Q000150:complications / Q000175:diagnosis / Q000453:epidemiology*; D012307:Risk Factors
D006710:Homocysteine