title: Homocysteine and ischemic heart disease: results of a prospective study with implications regarding prevention.
abstract: 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.
authors.affiliation: Department of Environmental and Preventive Medicine, Wolfson Institute of Preventive Medicine, St Bartholomew's and the Royal London School of Medicine and Dentistry, England.
authors.forename: N J
authors.initials: NJ
authors.lastname: Wald
authors.forename: H C
authors.initials: HC
authors.lastname: Watt
authors.forename: M R
authors.initials: MR
authors.lastname: Law
authors.forename: D G
authors.initials: DG
authors.lastname: Weir
authors.forename: J
authors.initials: J
authors.lastname: McPartlin
authors.forename: J M
authors.initials: JM
authors.lastname: Scott
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000097:blood* / Q000517:prevention & control; D016017:Odds Ratio; D011446:Prospective Studies; D012189:Retrospective Studies; D012307:Risk Factors
chemical_list: D006710:Homocysteine