Homocysteine

Homocysteine

SST (Tiger Top) Lithium Heparin/ Potassium EDTA

Homocysteine (HCY) is a thiol-containing amino acid produced by the intracellular demethylation of methionine. Homocysteine is exported into plasma where it circulates, mostly in its oxidized form, bound to plasma proteins as a protein-HCY mixed disulfide with albumin. Smaller amounts of reduced homocysteine and the disulfide homocystine (HCY-SS-HCY) are present. Total homocysteine (tHCY) represents the sum of all homocysteine species found in serum or plasma (free plus protein bound). Homocysteine is metabolized to either cysteine or methionine. In the vitamin B6 dependent trans-sulphuration pathway, homocysteine is irreversibly catabolized to cysteine. A major part of homocysteine is remethylated to methionine, mainly by the folate and cobalamin dependent enzyme methionine synthase. Homocysteine accumulates and is excreted into the blood when these reactions are impaired. Impaired homocysteine metabolism results in hyperhomocysteinemia (increased levels of homocysteine in plasma or serum) or homocystinuria (high plasma levels cause homocysteine to be excreted in urine). Hyperhomocysteinemia is caused by nutritional and genetic deficiencies. The majority of elevated homocysteine cases (two-thirds) in the general population are due to deficiency of folic acid, vitamin B6 and vitamin B12.

Severely elevated concentrations of total homocysteine are found in subjects with homocystinuria, a rare genetic disorder of the enzymes involved in the metabolism of homocysteine. Patients with homocystinuria exhibit mental retardation, early arteriosclerosis and arterial and venous thromboembolism. Other less severe genetic defects which lead to moderately elevated levels of total homocysteine are also found. Studies have investigated the relationship between elevated homocysteine concentrations and cardiovascular disease (CVD), indicating homocysteine as an important marker for risk assessment. In the presence of known coronary artery disease (CAD), it has been shown to be a strong independent marker of subsequent CAD-related death. A study conducted on 1933 elderly men and women from the Framingham Heart Study cohort demonstrated that elevated levels of homocysteine are independently associated with increased rates of all-cause and cardiovascular disease mortality. In intermediate risk patients, elevated homocysteine levels are associated with the quantity of coronary artery calcification. Elevated homocysteine levels in these patients are independent of coronary heart disease (CHD) risk factors.

A meta-analysis of 27 epidemiological studies, including more than 4000 patients, estimated that a 5 μmol/L increase in total homocysteine was associated with an odds ratio for CAD of 1.6 (95% confidence interval [CI], 1.4 to 1.7) for men and 1.8 (95% CI, 1.3 to 1.9) for women; the odds ratio for cerebrovascular disease was 1.5 (95% CI, 1.3 to 1.9). The risk associated with a 5 μmol/L increase in total homocysteine was the same as that 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. An elevated concentration of total homocysteine is a frequently observed finding in the blood of these patients. Although they may lack some of the vitamins involved in the metabolism of homocysteine, the increased levels of total homocysteine are mainly due to impaired removal of homocysteine from the blood by the kidneys.

It has been suggested that elevated homocysteine is a modifiable, independent risk factor for CAD, stroke and deep vein thrombosis. Studies have also identified elevated homocysteine as a strong independent risk factor for developing various forms of dementia, including Alzheimer’s Disease. In one study consisting of 1092 subjects from the Framingham Study, plasma homocysteine levels > 14 μmol/L doubled the risk of Alzheimer’s Disease. A study has indicated plasma tHCY levels are lower in pregnant women than non-pregnant women (mean tHCY is approximately 5-6 μmol/L, values > 10 μmol/L are rarely observed). Increased tHCY is associated with increased risk of pregnancy complications (preeclampsia, recurrent early pregnancy loss, premature delivery, low birth weight, and placental abruption or infarction). Maternal hyperhomocysteinemia is related to birth defects such as neural tube defects, orofacial clefts, club foot and Down’s Syndrome.

<15.0 umol/L