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Plasma total homocysteine: instigator or indicator of cardiovascular disease?

Stuart J Moat1

  • 1Department of Medical Biochemistry and Immunology, University Hospital of Wales and Wales College of Medicine, Heath Park, Cardiff CF14 4XW, UK. Stuart.moat@cardiffandvale.wales.nhs.uk

Annals of Clinical Biochemistry
|June 28, 2008
PubMed

Insights

High homocysteine levels are linked to cardiovascular disease (CVD), but lowering them with B-vitamins does not reduce CVD risk. This suggests homocysteine is an indicator, not a cause, of CVD.

Area of Science:

  • Cardiovascular Medicine
  • Biochemistry
  • Nutritional Science

Background:

  • Cardiovascular disease (CVD) remains a leading cause of death globally.
  • Traditional risk factors do not fully explain CVD incidence.
  • Plasma total homocysteine (tHcy) emerged as a potential modifiable CVD risk factor.

Purpose of the Study:

  • To evaluate the clinical benefit of lowering plasma tHcy concentrations on CVD risk.
  • To test the 'homocysteine hypothesis' which posits that reducing tHcy with B-vitamins mitigates CVD.

Main Methods:

  • Meta-analyses of epidemiological studies were reviewed.
  • Results from large randomized controlled trials (RCTs) investigating tHcy lowering were analyzed.
  • Experimental data on homocysteine's effects (oxidative stress, endothelial dysfunction, thrombogenesis) were considered.

Main Results:

  • Epidemiological studies show an association between elevated tHcy and CVD.
  • Experimental studies demonstrate homocysteine's detrimental effects on vascular health.
  • Large RCTs found no clinical benefit in reducing CVD risk by lowering plasma tHcy with folic acid and B-vitamins.

Conclusions:

  • The 'homocysteine hypothesis' is not supported by clinical trial data.
  • Lowering plasma tHcy concentrations does not appear to reduce CVD risk.
  • Homocysteine is likely a marker or indicator of CVD rather than a direct causative agent.

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