OBJECTIVE: Prospective assessment of the risk of coronary heart disease associated with total serum homocyst(e)ine (homocysteine) concentration. DESIGN: Nested case-control study. SETTING: Caerphilly and surrounding villages in south Wales, UK. PARTICIPANTS: 2290 men who participated in phase II of the study in 1984. After a mean follow up of 10 years, 312 men developed coronary heart disease and were compared with 1248 randomly selected, age frequency matched controls. MAIN OUTCOME MEASURE: Acute myocardial infarction or death from coronary heart disease. RESULTS: The geometric mean serum homocysteine concentration was higher in cases (12.2 micromol/l, 95% confidence interval (CI) 11.8 to 12.6 micromol/l) than in controls (11.8 micromol/l, 95% CI 11.3 to 12.5 micromol/l) (p = 0.09). There was a graded increase in the odds ratio of coronary heart disease across quintiles of the homocysteine concentration distribution compared with the first (p = 0.04), which was attenuated when adjusted for confounding variables (p = 0.4). There was a small but non-significant increase in the adjusted odds ratio of coronary heart disease per standard deviation change in the log distribution of homocysteine concentration (OR = 1.07 (95% CI.93 to 1.24), p = 0.34). Comparing the top quintile of the homocysteine concentration with the remaining 80%, the adjusted odds ratio of coronary heart disease was 1.03 (95% CI 0.73 to 1.45) (p = 0.8) and comparing the top 5% with the remaining 95% it was 1.05 (95% CI 0.56 to 1.95) (p = 0.9). CONCLUSIONS: These findings do not support the hypothesis that a raised homocysteine concentration is a strong independent risk factor for coronary heart disease. Randomised controlled trials of homocysteine lowering treatment such as folic acid are needed before generalizing the early positive results of observational studies.
OBJECTIVE: Prospective assessment of the risk of coronary heart disease associated with total serum homocyst(e)ine (homocysteine) concentration. DESIGN: Nested case-control study. SETTING: Caerphilly and surrounding villages in south Wales, UK. PARTICIPANTS: 2290 men who participated in phase II of the study in 1984. After a mean follow up of 10 years, 312 men developed coronary heart disease and were compared with 1248 randomly selected, age frequency matched controls. MAIN OUTCOME MEASURE: Acute myocardial infarction or death from coronary heart disease. RESULTS: The geometric mean serum homocysteine concentration was higher in cases (12.2 micromol/l, 95% confidence interval (CI) 11.8 to 12.6 micromol/l) than in controls (11.8 micromol/l, 95% CI 11.3 to 12.5 micromol/l) (p = 0.09). There was a graded increase in the odds ratio of coronary heart disease across quintiles of the homocysteine concentration distribution compared with the first (p = 0.04), which was attenuated when adjusted for confounding variables (p = 0.4). There was a small but non-significant increase in the adjusted odds ratio of coronary heart disease per standard deviation change in the log distribution of homocysteine concentration (OR = 1.07 (95% CI.93 to 1.24), p = 0.34). Comparing the top quintile of the homocysteine concentration with the remaining 80%, the adjusted odds ratio of coronary heart disease was 1.03 (95% CI 0.73 to 1.45) (p = 0.8) and comparing the top 5% with the remaining 95% it was 1.05 (95% CI 0.56 to 1.95) (p = 0.9). CONCLUSIONS: These findings do not support the hypothesis that a raised homocysteine concentration is a strong independent risk factor for coronary heart disease. Randomised controlled trials of homocysteine lowering treatment such as folic acid are needed before generalizing the early positive results of observational studies.
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