OBJECTIVES: To investigate the relationship between plasma folate, vitamin B12 and total homocysteine concentrations, dietary intake of folate and vitamins B12, B6 and B2, and the risk of first acute myocardial infarction (MI).

DESIGN: Nested case-referent study with up to 13 years of follow-up.

SETTING: The population-based Northern Sweden Health and Disease Study, with 73 879 participants at the time of case ascertainment.

SUBJECTS: A total of 571 MI cases (406 men) and 1569 matched referents. Of the cases, 530 had plasma samples available, and 247 had dietary B-vitamin intake data.

RESULTS: Plasma concentrations of folate were inversely associated, and total homocysteine positively associated, with the risk of MI, independently of each other and of a number of established and novel cardiovascular risk factors, including renal function [multivariate odds ratio for highest vs. lowest quintile of folate 0.52 (95% CI 0.31-0.84), P for trend = 0.036, and homocysteine 1.92 (95% CI 1.20-3.09), P for trend = 0.006]. For plasma vitamin B12 concentrations, and vitamin B12, B6 and B2 intake, no clear risk relationship was apparent. Though not statistically significant, the results for folate intake were consistent with those for plasma concentrations.

CONCLUSIONS: In this large prospective study of a population without mandatory folic acid fortification, both folate and homocysteine were strongly associated with the risk of myocardial infarction, independently of each other and of renal function. Although randomized trials of folic acid supplementation are needed to determine causality, our findings highlight the potential importance of folate, or sources of folate, in incident cardiovascular disease.