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[Homocysteine and cardiovascular risk]
L Lutteri1, J P Chapelle, J Gielen
1Service de Chimie médicale, Université de Liège.
Insights
Homocystinuria, a genetic disorder causing high homocysteine (HCY) levels, accelerates atherosclerosis and heart disease. Early detection and treatment with vitamins like folic acid are crucial for managing this cardiovascular risk factor.
Area of Science:
- Biochemistry and Genetics
- Cardiovascular Medicine
Context:
- Homocystinuria is a rare genetic disorder marked by elevated serum homocysteine (HCY).
- Hyperhomocysteinemia is an independent risk factor for cardiovascular disease, even without genetic defects.
Purpose:
- To elucidate the mechanisms by which elevated homocysteine contributes to atherogenesis.
- To highlight the role of B vitamins (folic acid, B12, B6) in managing hyperhomocysteinemia.
- To discuss the evolving diagnostic landscape for homocysteine determination.
Summary:
- Elevated homocysteine promotes atherosclerosis through mechanisms including LDL oxidation, endothelial dysfunction, smooth muscle cell proliferation, and interference with coagulation/fibrinolysis.
- Treatment involves B vitamins, which are cofactors for homocysteine metabolism.
- Homocysteine levels are assessed via basal plasma concentration or methionine loading tests.
- Diagnostic methods are shifting from complex laboratory techniques to widely available automated immunoassays.
Impact:
- Understanding homocysteine's atherogenic potential informs cardiovascular disease risk assessment.
- Highlights the therapeutic importance of B vitamins in managing hyperhomocysteinemia.
- Increased accessibility of homocysteine testing can lead to earlier diagnosis and intervention.
Abstract:
Homocystinuria is an uncommon genetic disease characterized by a marked increase of serum homocysteine (HCY), an intermediate of methionine metabolism. In patients with homocystinuria, hyperhomocysteinemia promotes the development of atherosclerotic lesions and is responsible for premature coronary artery disease. Recently, several studies have also demonstrated that moderate hyperhomocysteinemia--not necessarily linked to an inborn metabolic defect--may also be considered as an independant risk factor for cardiovascular disease. The main mechanisms of HCY atherogenic action are thought to be LDL oxydation, inhibition of vascular endothelium growth combined with stimulation of smooth muscular cells proliferation, and interference with the coagulation and fibrinolytic systems. Cofactors of key enzymes in HCY metabolism, folic acid, vitamin B12 and vitamin B6, may be given, alone or in combination, for the treatment of hyperhomocysteinemia. Homocysteinemia can be assessed by basal plasma HCY concentration and/or by HCY levels measured after a methionine loading test. Mainly measured till now in specialized laboratories using rather complex techniques (HPLC, GCMS, amino acid analyser ...), HCY determination is today spreading widely owing to the development of automated immunoassays.