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Homocysteine, renal function, and risk of cardiovascular disease
Robert Clarke1, Sarah Lewington, Martin Landray
1Clinical Trial Service Unit, Radcliffe Infirmary, Oxford, United Kingdom. robert.clarke@ctsu.ox.ac.uk
Insights
Elevated homocysteine levels in patients with kidney disease increase the risk of heart disease and stroke. Lowering homocysteine may reduce vascular risks, but more research is needed.
Area of Science:
- Cardiovascular epidemiology
- Renal medicine
- Nutritional science
Background:
- Patients with renal impairment exhibit high homocysteine levels, posing a significant risk for ischemic heart disease (IHD) and stroke.
- The precise role of elevated homocysteine in this population's vascular risk remains unclear.
Purpose of the Study:
- To investigate the association between homocysteine levels and vascular disease in individuals with impaired renal function.
- To explore the relationship between renal function and homocysteine concentrations.
Main Methods:
- Meta-analysis of 30 population studies on homocysteine and vascular events (5000 IHD, 1100 stroke).
- Meta-analysis of 40 studies on methylene-tetrahydrofolate reductase (MTHFR) genotype, homocysteine, and IHD (11,000 IHD events).
- Cross-sectional study of 1200 elderly individuals examining renal function and homocysteine levels.
Main Results:
- A 25% reduction in homocysteine was linked to an 11% lower IHD risk and 20% lower stroke risk.
- Individuals with the MTHFR TT genotype had 25% higher homocysteine and a 16% increased IHD risk compared to CC genotype.
- In elderly individuals, a 1% increase in serum creatinine correlated with a 1% increase in homocysteine.
Conclusions:
- The consistent findings across genetic and population studies suggest a causal link between homocysteine and IHD.
- Renal function significantly influences circulating homocysteine levels.
- Further randomized trials on folic acid supplementation in renal patients are essential to confirm homocysteine's role in vascular disease prevention.
Background:
Patients with renal impairment have markedly elevated homocysteine levels and are at particularly high risk of ischemic heart disease (IHD) and stroke, but the relevance of elevated homocysteine levels in this population is uncertain.
Methods:
We examined the association with IHD from a meta-analysis of 30 population studies of differences in homocysteine concentrations (involving 5000 IHD and 1100 stroke events in apparently healthy individuals), and from a meta-analysis of 40 studies (involving 11,000 IHD events) of the association of methylene-tetrahydrofolate reductase (MTHFR) and homocysteine with IHD. We explored the association of renal function with homocysteine levels in a cross-sectional study of 1200 healthy elderly individuals.
Results:
Among prospective studies, a 25% lower blood homocysteine level was associated with an 11% lower risk of IHD and about a 20% lower risk of stroke, after adjustment for known cardiovascular risk factors. Individuals who had the TT genotype for MTHFR compared with those with CC had 25% higher homocysteine levels and a 16% higher risk of IHD. Among individuals aged over 65 years, a 1% higher serum creatinine level was associated with about a 1% higher homocysteine concentration.
Conclusions:
The concordance of the IHD risks obtained in the studies of genetically determined differences in homocysteine and the population-based studies of homocysteine suggest that these associations are likely to be causal. Renal function is an important determinant of circulating homocysteine concentrations. Results of ongoing randomized trials of folic acid-based vitamins in patients with renal disease are required to clarify the relevance of lowering homocysteine for vascular disease.