Homocysteine and risk of cardiovascular disease.
This pictorial introduction to homocysteine illustrates at a glance the nature of homocysteine and its role in cardiovascular disease by means of eight simple figures and an essential bibliography. Homocysteine is a sulfur-containing metabolite of methionine. Conversion back to methionine or transsulfuration to cysteine are the two major metabolic pathways that reduce total homocysteine (tHcy) concentrations in cells and blood. B vitamins are essential cofactors in homocysteine metabolism. Median fasting total homocysteine levels in adult males are approximately 10 micromol/L. Increased plasma tHcy concentrations are found with methionine-rich diets, low vitamin B intake, male gender, age, impaired renal function, and genetically determined defects of the enzymes involved in homocysteine metabolism. An inverse relation exists between plasma tHcy and circulating folate or vitamin B(6) concentrations, and folic acid supplements of 0.5 mg/d can reduce tHcy levels by approximately 25%. Homocystinuric patients, who have severe hyperhomocysteinemia, die prematurely of atherothrombotic disease. Many (but not all) cross-sectional and prospective studies indicate, on average, that plasma tHcy levels <.10 micromol/L are associated with, or predict the development of, coronary, cerebral, and peripheral vascular disease. The risk conferred by hyperhomocysteinemia is graded and is independent of traditional risk factors, with an estimated odds ratio for ischemic heart disease of 1.4 for every 5 micromol/L increase in plasma tHcy. In vitro and in vivo, tHcy has been found to impair endothelial function. It is now well established that tHcy represents a marker of current or subsequent ischemic vascular disease. However, irrefutable proof that hyperhomocysteinemia actually causes atherothrombosis will come only if interventions to lower plasma tHcy will produce concomitant reductions in cardiovascular events.
Andreotti
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Institute of Cardiology, Catholic University, Rome, Italy. felicita.andreotti@iol.it
Burzotta
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Manzoli
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Robinson
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D001161:Arteriosclerosis / Q000097:blood / Q000209:etiology; D015415:Biomarkers / Q000097:blood; D002318:Cardiovascular Diseases / Q000097:blood / Q000453:epidemiology* / Q000209:etiology*; D006710:Homocysteine / Q000097:blood* / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D020138:Hyperhomocysteinemia / Q000097:blood / Q000150:complications; D012307:Risk Factors; D013927:Thrombosis / Q000097:blood / Q000209:etiology
D015415:Biomarkers; D006710:Homocysteine