Folate in the United States Population and its Association with Congestive Heart Failure

Background: To investigate the relationship between red blood cell (RBC) folate and congestive heart failure (CHF). Methods: We extracted the concentrations of RBC folate and collated CHF information from the National Health and Nutrition Examination Survey (NHANES) survey (12820 individuals). Weighted univariate logistic regression, weighted multivariate logistic regression, and restrictive cubic spline (RCS) were used to assess the relationship between RBC folate concentrations and CHF. Results: The unadjusted model showed that the highest tertile group of RBC folate concentration was significantly associated with a higher risk of CHF compared to the lowest tertile group of RBC folate levels (odds ratio [OR] = 3.09; 95% confidence interval [CI], 2.14-4.46). Similar trends were seen in the multivariate-adjusted analysis (OR = 1.98; 95% CI: 1.27-3.09). The OR was >1.0 when the predicted RBC folate exceeded 2757 nmol/L in the RCS model, indicating that the risk of CHF was low and relatively stable up to a predicted RBC folate level of 2757 nmol/L, but began to increase rapidly thereafter (p = 0.001). Conclusions: The risk of CHF may be increased either by high RBC folate concentrations (highest tertile of RBC folate or >2637 nmol/L) or by folate deficiency. Considering the two sides of the association between RBC folate and CHF, there is a need for large-scale clinical research to better investigate if the association between RBC folate and CHF is a cause-effect relationship, what are the underlying pathophysiological basis, as well as to identify optimal dietary folate equivalent (DFE) and RBC folate concentration intervals.