Associations of Serum Folate and Vitamin B12 levels with Cardiovascular Mortality among Non-diabetic Population

BackgroundWhile studies have examined the associations between folate, vitamin B12, and cardiovascular mortality in high-risk populations, evidence regarding these associations in non-diabetic population remains limited. This study aimed to assess the associations of serum folate and vitamin B12 levels with cardiovascular mortality in a large, nationally representative cohort of US non-diabetic adults. Methods and ResultsData were extracted from the National Health and Nutrition Examination Survey (NHANES) cycles from 1999 to 2006 and 2011 to 2014. Multivariate logistic regression and restricted cubic spline (RCS) analyses were used to evaluate the associations between serum folate, vitamin B12 and cardiovascular mortality. A two-piecewise logistic regression model was employed to identify the inflection points of serum folate and vitamin B12 levels on cardiovascular mortality. Among 19,402 US adults, the mean age was 43.9 {+/-} 18.6 years, 9,749 (50.2%) were male, and 8,438 (43.5%) were non-Hispanic White. With a median follow-up of 159 months (IQR: 82.0-193.0 months), 928 cardiovascular deaths were documented. After fully adjusting for potential confounders, a significant inverse association was observed between serum folate levels and cardiovascular mortality. The RCS analysis revealed non-linear associations between serum folate (P for nonlinearity = 0.02), vitamin B12 levels (P for nonlinearity = 0.04), and the risk of cardiovascular mortality. Specifically, serum folate levels below 19.50 ng/mL and serum vitamin B12 levels at or above 436.52 pg/mL were both linked to an increased risk of cardiovascular mortality. Stratified and sensitivity analyses confirmed the robustness of these associations. ConclusionsThis study demonstrated that low serum folate levels and high vitamin B12 levels were associated with an increased risk of cardiovascular mortality in non-diabetic individuals. These findings provide evidence supporting the potential of serum folate and vitamin B12 levels as biomarkers for cardiovascular mortality risk estimation, pending further validation in other independent cohorts.