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

## TL;DR

This study explores how red blood cell folate levels in the U.S. population are linked to an increased risk of congestive heart failure.

## Contribution

The study reveals a non-linear association between RBC folate concentrations and CHF risk, suggesting a potential threshold for optimal folate levels.

## Key findings

- High RBC folate levels (highest tertile) are significantly associated with increased CHF risk.
- CHF risk increases rapidly when RBC folate exceeds 2757 nmol/L.
- Both folate deficiency and excess may contribute to CHF risk.

## Abstract

To investigate the relationship between red blood cell
(RBC) folate and congestive heart failure (CHF).

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.

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).

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.