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Homocysteine and ischemic heart disease: results of a prospective study with implications regarding prevention
1Department of Environmental and Preventive Medicine, Wolfson Institute of Preventive Medicine, St Bartholomew's and the Royal London School of Medicine and Dentistry, England.
Insights
Higher serum homocysteine levels significantly increase ischemic heart disease (IHD) risk. Increasing folic acid intake may reduce IHD mortality.
Area of Science:
- Cardiovascular Epidemiology
- Nutritional Science
- Biochemistry
Background:
- Prospective studies on serum homocysteine and ischemic heart disease (IHD) have yielded inconclusive results.
- Further research is needed to clarify the association between homocysteine levels and IHD risk.
Purpose of the Study:
- To investigate the relationship between serum homocysteine levels and the risk of developing IHD.
- To determine if elevated homocysteine is a causal factor in IHD.
Main Methods:
- A nested case-control design was employed within the British United Provident Association (BUPA) prospective study.
- Serum homocysteine levels were measured in 229 men who died of IHD and 1126 age-matched controls.
Main Results:
- Men who died of IHD had significantly higher serum homocysteine levels compared to controls (13.1 vs 11.8 micromol/L).
- The highest quartile of homocysteine was associated with a 3.7-fold increased IHD risk, which persisted after adjusting for other risk factors (2.9-fold).
- A continuous dose-response relationship was observed, with a 41% increased risk for every 5-micromol/L increase in homocysteine.
Conclusions:
- The study's findings help resolve previous uncertainties regarding the homocysteine-IHD link.
- Epidemiological, genetic, and animal evidence suggest a likely causal association between serum homocysteine and IHD.
- Increased folic acid consumption, which lowers homocysteine, is expected to reduce IHD mortality.
Background:
Results from prospective studies of serum homocysteine levels and ischemic heart disease (IHD) are inconclusive. We carried out a further prospective study to help clarify the position.
Methods:
In the British United Provident Association (BUPA) prospective study of 21,520 men aged 35 to 64 years, we measured homocysteine levels in stored serum samples and analyzed data from 229 men without a history of IHD at study entry who subsequently died of IHD and 1126 age-matched control subjects (nested case-control design).
Results:
Serum homocysteine levels were significantly higher in men who died of IHD than in men who did not (mean, 13.1 vs 11.8 micromol/L; P<.001). The risk of IHD among men in the highest quartile of serum homocysteine levels was 3.7 times (or 2.9 times after adjusting for other risk factors) the risk among men in the lowest quartile (95% confidence interval [CI], 1.8-4.7). There was a continuous dose-response relationship, with risk increasing by 41% (95% CI, 20%-65%) for each 5-micromol/L increase in the serum homocysteine level. After adjustment for apolipoprotein B levels and blood pressure, this estimate was 33% (95% CI, 22%-59%). In a meta-analysis of the retrospective studies of homocysteine level and myocardial infarction, the age-adjusted association was stronger: an 84% (95% CI, 52%-123%) increase in risk for a 5-micromol/L increase in the homocysteine level, possibly because the participants were younger; the relationship between serum homocysteine level and IHD seems to be stronger in younger persons than in older persons.
Conclusions:
Our positive results help resolve the uncertainty that resulted from previous prospective studies. The epidemiological, genetic, and animal evidence together indicate that the association between serum homocysteine level and IHD is likely to be causal. A general increase in consumption of the vitamin folic acid (which reduces serum homocysteine levels) would, therefore, be expected to reduce mortality from IHD.