[Homocysteine, endothelial dysfunction and cardiovascular risk: pathomechanisms and therapeutic options].
Elevated homocyst(e)ine plasma concentrations are an independent risk factor for cardiovascular disease. Hyperhomocyst(e)inaemia is common in patients with peripheral arterial occlusive disease, coronary heart disease, cerebrovascular disease, carotid artery stenosis and venous thromboembolism. Endothelial dysfunction may be one underlying cause leading to proatherogenic effects associated with hyperhomocyst(e)inaemia. However, the mechanisms which lead to impaired endothelial function in hyperhomocyst(e)inaemia are not fully understood. Recent evidence suggests that homocyst(e)ine may interact with physiological mediators of the endothelial matrix. Oxidative mechanisms and decreased biological activity of endothelium-derived nitric oxide (NO) may also contribute to homocyst(e)ine-associated endothelial dysfunction. B vitamins are essential cofactors in the metabolism of homocyst(e)ine to methionine via the remethylation-pathway (vitamin B12, folic acid) and to cystathionine via the transsulphuration-pathway (vitamin B6). Dietary deficiencies of folic acid, vitamin B12, and vitamin B6 appear to be common among elderly people in the western world and represent one pathogenic factor related to the incidence of hyperhomocyst(e)inaemia. Several studies have demonstrated that dietary supplementation with folic acid and the vitamins B12 and B6 is an efficient means to decrease plasma homocyst(e)ine. No clinical studies are available to date to prove whether reducing homocyst(e)ine levels to the normal range by supplementary B vitamins will also beneficially affect vascular function or cardiovascular risk. Furthermore it is unknown whether moderately elevated homocyst(e)ine concentrations per se may predispose to development of vascular disease, or whether homocyst(e)ine is an indirect marker of cardiovascular disease. Further investigations will be necessary to elucidate the causal relationship between elevated homocyst(e)ine plasma concentrations and the incidence of cardiovascular events, especially since the therapeutic strategies in hyperhomocyst(e)inaemia would differ depending on the underlying pathophysiological mechanisms.
Sydow
K
K
Klinik und Poliklinik für Innere Medizin Abteilung Kardiologie Unversitätsklinikum Hamburg-Eppendorf Martinistrasse 52 20246 Hamburg.
Böger
R H
RH
D000328:Adult; D000368:Aged; D002318:Cardiovascular Diseases / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology; D002986:Clinical Trials as Topic; D004359:Drug Therapy, Combination; D004730:Endothelium, Vascular / Q000502:physiology / Q000503:physiopathology*; D005260:Female; D005342:Fibrinolysis; D005492:Folic Acid / Q000008:administration & dosage / Q000627:therapeutic use; D005500:Follow-Up Studies; D006710:Homocysteine / Q000097:blood / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D020138:Hyperhomocysteinemia / Q000188:drug therapy* / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000502:physiology; D018384:Oxidative Stress; D013997:Time Factors; D014803:Vitamin B Complex / Q000008:administration & dosage / Q000627:therapeutic use*
D006710:Homocysteine; D014803:Vitamin B Complex; D009569:Nitric Oxide; D005492:Folic Acid
Homocyst(e)in, endotheliale Dysfunktion und kardiovaskuläres Risiko. Pathomechanismen und therapeutische Optionen.