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[Homocysteine, endothelial dysfunction and cardiovascular risk: pathomechanisms and therapeutic options]
1Klinik und Poliklinik für Innere Medizin Abteilung Kardiologie Unversitätsklinikum Hamburg-Eppendorf Martinistrasse 52 20246 Hamburg.
Insights
High homocysteine levels increase cardiovascular disease risk. B vitamin supplements can lower homocysteine, but their effect on vascular health needs more study.
Area of Science:
- Cardiovascular Medicine
- Nutritional Science
- Biochemistry
Background:
- Elevated plasma homocysteine is an independent risk factor for cardiovascular diseases like coronary heart disease and stroke.
- Hyperhomocysteinemia is prevalent in patients with various vascular conditions, including peripheral arterial occlusive disease and venous thromboembolism.
- Endothelial dysfunction, potentially involving oxidative stress and reduced nitric oxide activity, is a proposed mechanism linking homocysteine to vascular damage.
Purpose of the Study:
- To review the role of homocysteine in cardiovascular disease and endothelial dysfunction.
- To examine the impact of B vitamin deficiencies and supplementation on homocysteine metabolism and plasma levels.
- To highlight the need for clinical studies to confirm the vascular benefits of homocysteine reduction.
Main Methods:
- Literature review of studies on homocysteine, B vitamins, and cardiovascular disease.
- Analysis of mechanisms underlying homocysteine-induced endothelial dysfunction.
- Evaluation of current evidence on B vitamin supplementation for lowering homocysteine.
Main Results:
- Dietary deficiencies in folic acid, vitamin B12, and vitamin B6 are common and contribute to elevated homocysteine.
- Supplementation with these B vitamins effectively reduces plasma homocysteine concentrations.
- No clinical trials currently demonstrate that lowering homocysteine with B vitamins improves vascular function or reduces cardiovascular risk.
Conclusions:
- While B vitamins effectively lower homocysteine, their direct impact on cardiovascular outcomes remains unproven.
- Further research is crucial to establish a causal link between elevated homocysteine and cardiovascular events.
- Understanding the precise role of homocysteine is essential for developing targeted therapeutic strategies.
Abstract:
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.