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Catherine M. Loria, PhD; Deborah D. Ingram, PhD; Jacob J. Feldman, PhD; Jacqueline D. Wright, MPH; Jennifer H. Madans, PhD

Arch Intern Med. 2000;160:3258-3262.

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.

From the National Center for Health Statistics, Centers for Disease Control and Prevention, Hyattsville Md. Dr Loria is now with the National Heart, Lung, and Blood Institute, Bethesda, Md. Dr Feldman is now with the Center for Health Affairs, Project HOPE, Bethesda, Md.

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