HOMOCYSTEINE AND ISCHEMIC-HEART-DISEASE - RESULTS OF A PROSPECTIVE-STUDY WITH IMPLICATIONS REGARDING PREVENTION

Background: Results from prospective studies of serum homocysteine lev els 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 2 1520 men aged 35 to 64 years, we measured homocysteine levels in store d serum samples and analyzed data from 229 men without a history of ii -ID at study entry who subsequently died of IHD and 1126 age-matched c ontrol subjects (nested case-control design). Results: Serum homocyste ine levels were significantly higher in men who died of IHD than in me n who did not (mean, 13.1 vs 11.8 mu mol/L; P<.001). The risk of IHD a mong 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 a mong men in the lowest quartile (95%:, confidence interval [CI], 1.8-4 .7). There was a continuous dose-response relationship, with risk incr easing by 41% (95% CI, 20%-65%) for each 5-mu mol/L increase in the se rum homocysteine level. After adjustment for apolipoprotein B levels a nd blood pressure, this estimate was 33% (95% CI, 22%-59%). In a metaa nalysis of the retrospective studies of homocysteine level and myocard ial infarction, the age-adjusted association was stronger: an 84% (95% CI, 52%-123%) increase in risk for a 5-mu mol/L increase in the homoc ysteine level, possibly because the participants were younger; the rel ationship between serum homocysteine level and IHD seems to be stronge r in younger persons than in older persons. Conclusions: Our positive results help resolve the uncertainty that resulted from previous prosp ective studies. The epidemiological, genetic, and animal evidence toge ther indicate that the association between serum homocysteine level an d IHD is likely to be causal. A general increase in consumption of the vitamin folic acid (which reduces serum homocysteine levels) would, t herefore, be expected to reduce mortality from IHD.