Serum folate and cardiovascular disease mortality among US men and women

Background: Folate has been linked to cardiovascular disease (CVD) through its role in homocysteine metabolism. Objective: To assess the relationship between serum folate and CVD mortality. Design: In this prospective study, serum folate concentrations were measured on a subset of adults during the Second National Health and Nutrition Examination Survey (1976-1980) and vital status ascertained after 12 to 16 years. Setting and Patients: A national probability sample consisting of 689 adults who were 30 to 75 years of age and did not have a history of CVD at baseline. Main Outcome Measure: Vital status was determined by searching national databases that contained information about US decedents. Results: The associations between serum folate and CVD and all-cause mortality differed by diabetes status (P=.04 and P=.03, respectively). Participants without diabetes in the lowest compared with the highest serum folate tertile had more than twice the risk of CVD mortality after adjustment for age and sex (relative risk [RR], 2.64; 95% confidence interval [CI], 1.15-6.09). This increased risk for participants in the lowest tertile was attenuated after adjustment for CVD risk factors (RR, 2.28; 95% CI, 0.96-5.40). Serum folate tertiles were not significantly associated with total mortality, although the age- and sex-adjusted risk was increased for participants in the lowest compared with highest tertile (RR, 1.74; 95% CI, 0.96-3.15). Risk estimates for participants with diabetes were unstable because of the small sample size (n=52). Conclusion: These data suggest that low serum folate concentrations are associated with an increased risk of CVD mortality among adults who do not have diabetes.