Homocysteine and cerebral infarction in Finnish male smokers

Background and Purpose - Homocysteine is associated with stroke, but it is not clear whether this relationship is causal. We examined the association between total serum homocysteine concentration (tHcy) and cerebral infarction in a cohort of Finnish male smokers. Methods - This is a matched case-control study of 201 cases of cerebral infarction and 201 concurrently sampled age-matched controls nested in a cohort of 13 840 male smokers free of cardiovascular disease at the completion of the Alpha-Tocopherol and Beta-Carotene ( ATBC) Cancer Prevention study. Conditional logistic regression was used to calculate odds ratios (ORs) and to adjust for confounding variables. An unmatched analysis was also performed. Results - The geometric mean tHcy was 13.3 +/- mumol/L (95% CI, 12.6 to 13.9) in cases and 12.6 mumol/L ( 95% CI, 12.0 to 13.2) in controls ( P = 0.09). There was a graded increase in the OR of cerebral infarction per quartile increase in tHcy ( OR, 1.0, 1.7, 1.9, 2.1; trend P = 0.02; 201 case-control pairs) when adjusted for traditional risk factors. There was a similar trend in a subgroup of 120 case-control pairs for which further adjustment for lifestyle factors was possible ( OR, 1.0, 1.9, 2.5, 2.2; trend P = 0.07 in the matched analyses; OR, 1.0, 1.2, 1.9, 2.0; trend P = 0.02 in the unmatched analyses). The adjusted OR per 1-SD increase in log-transformed tHcy ( equivalent to 4.7 mumol) was 1.4 ( 95% CI, 1.1 to 1.7; P = 0.01). Conclusions - tHcy appears to predict cerebral infarction in Finnish male smokers.