Serum homocysteine, folate and risk of stroke: Kuopio Ischaemic Heart Disease Risk Factor (KIHD) Study

Abstract

Background: Homocysteine and folate have been suggested to have opposite effects on the risk of stroke, although the results are controversial.

Design and methods: The purpose of this study was to assess the effects of serum total homocysteine (tHcy) and serum folate levels on the risk of stroke in a prospective cohort study. The subjects were 1015 men aged 46-64 years and free of prior stroke, examined in 1991-1993 in the Kuopio Ischaemic Heart Disease Risk Factor (KIHD) Study.

Results: At baseline the mean serum tHcy concentration was 10.9 micromol/l (SD 3.4). During an average follow-up time of 9.6 years, 49 men experienced a stroke, of which 34 were ischaemic. In Cox proportional hazards models, men in the highest tHcy third had a risk factor-adjusted hazard rate ratio (RR) of 2.77 [95% confidence interval (CI): 1.23-6.24] for any stroke and 2.61 (95% CI: 1.02-6.71) for ischaemic stroke, compared with men in the lowest third. The mean baseline serum folate concentration was 10.4 nmol/l (SD 4.1). Men in the highest third of serum folate (>11.2 nmol/l) had an adjusted RR for any stroke of 0.35 (95% CI: 0.14-0.87) and for ischaemic stroke of 0.40 (95% CI: 0.15-1.09), compared with men in the lowest third.

Conclusion: Elevated serum tHcy is associated with increased risk of all strokes and ischaemic strokes in middle-aged eastern Finnish men free of prior stroke. On the other hand, high serum folate concentration may protect against stroke.