Related Experiment Videos
[Hyperhomocysteinemia: an independent risk factor or a simple marker of vascular disease? 2. Epidemiological data]
J-C Guilland1, A Favier, G Potier de Courcy
1Laboratoire de physiologie, UFR de médecine, BP 87900, 21079 cedex, Dijon, France. jean-claude.guilland@chu-dijon.fr <jean-claude.guilland@chu-dijon.fr>
Insights
Elevated total homocysteine (tHcy) may not be a direct cause of cardiovascular disease (CVD). Further research, including intervention studies, is needed to clarify the relationship between tHcy and CVD risk.
Area of Science:
- Cardiovascular Science
- Metabolic Disease Research
- Clinical Epidemiology
Background:
- Elevated plasma total homocysteine (tHcy) is a suspected risk factor for occlusive cardiovascular disease (CVD).
- This suspicion stems from observations in homocystinuria patients and prospective studies linking tHcy to increased CVD risk.
- However, conflicting evidence questions tHcy's causal role in CVD.
Purpose of the Study:
- To critically evaluate the evidence supporting total homocysteine (tHcy) as a causal risk factor for cardiovascular disease (CVD).
- To identify confounding factors and limitations in current research on tHcy and CVD.
- To determine the necessity of placebo-controlled intervention studies for definitive conclusions.
Main Methods:
- Review of existing prospective studies and genetic association data.
- Analysis of the association between tHcy and traditional CVD risk factors.
- Consideration of genetic variations, such as MTHFR C667T, and their impact on tHcy and CVD risk.
Main Results:
- Low-risk population studies often show a weak or no association between tHcy and CVD.
- Traditional CVD risk factors are frequently associated with tHcy, suggesting potential confounding.
- The MTHFR C667T polymorphism moderately increases tHcy but shows minimal or no increased CVD risk.
Conclusions:
- The causal link between elevated total homocysteine (tHcy) and cardiovascular disease (CVD) remains uncertain.
- Confounding factors and inconsistent findings challenge tHcy's role as an independent CVD risk factor.
- Placebo-controlled intervention trials using B-vitamins are essential to resolve the debate on tHcy's etiological role in CVD.
Abstract:
Elevated plasma total homocysteine (tHcy) is considered as a risk factor for occlusive cardiovascular disease (CVD). This concept is based on the observations of premature vascular disease in patients with homocystinuria and on the association between tHcy and increased risk of CVD in prospective studies. However, some observations have raised questions about tHcy as a risk factor. First, low risk population based prospective studies tend to indicate a weak association or no association between tHcy and CVD. Second, several traditional risk factors for CVD are associated with tHcy and may confound the relation between tHcy and CVD. Third, the C667T transition of the methylenetetrahydrofolate reductase causes a moderate increase in tHcy but no or only minor increased CVD risk. Thus, only placebo-controlled intervention studies with tHcy-lowering B-vitamins and clinical endpoints can provide additional valid arguments for the debate over whether tHcy is a causal CVD risk factor.