Homocysteine (Hcy) is a thiol-containing amino acid produced by the intracellular demethylation of methionine. Hcy is exported into plasma where it circulates mostly in its oxidized forms bound to plasma proteins. Smaller amounts of reduced homocysteine and disulfide homocystine (Hcy-SS-Hcy) are present. Total homocysteine represents the sum of all Hcy species found in plasma and serum (free plus protein-bound).
Epidemiological studies have investigated the relationship between Hcy levels in blood and cardiovascular disease (CVD). A meta analysis of 27 epidemiological studies, including more than 4000 patients, estimated that a 5 µmol/L increase in Hcy was associated with an odds ratio for coronary artery disease (CAD) of 1.6 for men and 1.8 for women, or the same that is associated with 0.5 mmol/L (20 mg/dL) increase in cholesterol. Peripheral arterial disease also showed a strong association.
Patients with chronic renal disease experience an excess morbidity and mortality due to arteriosclerotic CVD. Elevated concentration of Hcy is a frequently observed finding in the blood of these patients. Although such patients may lack some of the vitamins involved in the metabolism of Hcy, the increased levels of Hcy are mainly due to impaired removal of Hcy from the blood by the kidney.
Drugs such as methotrexate, carbamazepine, phenytoin, nitrous oxide and penicillamine interfere with the Hcy metabolism and may give elevated levels of Hcy.