# A preliminary study on the early warning role of DL-malic acid in atrial fibrillation occurrence among patients with hyperuricemia

**Authors:** Dayong Li, Huachen Jiao, Donghai Liu, Zeng Li, Shunxin Lv, Haoluo Jin, Xipeng Yan

PMC · DOI: 10.3389/fcvm.2025.1678453 · Frontiers in Cardiovascular Medicine · 2025-10-20

## TL;DR

This study explores how DL-malic acid and other metabolites may predict atrial fibrillation in patients with high uric acid levels.

## Contribution

Identifies DL-malic acid and other metabolites as potential early warning markers for atrial fibrillation in hyperuricemia patients.

## Key findings

- DL-malic acid, L-threonine, L-valine, and L-cysteine are potential early warning markers for AF in hyperuricemia patients.
- The combined ROC analysis of these metabolites showed strong predictive power with an AUC of 0.923 in the AFHUA/Control group.
- These findings suggest a new approach for predicting and managing atrial fibrillation in hyperuricemia patients.

## Abstract

There have been sufficient previous studies demonstrating that hyperuricemia (HUA) is closely associated with the occurrence of atrial fibrillation (AF).The incidence of AF in patients with hyperuricemia is higher than that in the general population. Therefore, it is meaningful to explore the serum markers of AF in the HUA population and establish early warning indicators.

To preliminarily explore the correlation between HUA and AF at the metabolomics level, and to identify a group of metabolites with potential predictive power for AF that can be used for further large-scale studies.

This study used untargeted metabolomics technology to detect serum metabolites of patients with AF, patients with AFHUA, and control group. Receiver operator characteristic (ROC) curve were used to analyze differential metabolites.

Ultimately, multiple metabolites such as L-Threonine, DL-Malic acid, L-Valine, L-Cysteine were identified as early warning markers of AF in patients with HUA. Combined ROC curve using these four metabolites between the AFHUA/Control comparison group and the AFHUA/AF comparison group showed good predictive efficacy, with Area Under the ROC Curve (AUC) = 0.923 (P < 0.001) in the AFHUA/Control comparison group and AUC = 0.714 (P < 0.001) in the AFHUA/AF comparison group. This provides an early predictive method for patients who may develop atrial fibrillation among those with hyperuricemia. And offers new approaches for the prevention and treatment of atrial fibrillation.

This study indicates that serum metabolomics can be specifically used to predict the probability of AF occurrence in individuals with HUA, and has identified metabolites such as L-Threonine, DL-Malic acid, L-Valine, and L-Cysteine that possess potential predictive efficacy.

The mechanism of action of DL-Malic acid and the TCA in the development of atrial fibrillation.Flowchart illustrating metabolic pathways related to cardiac health. The TCA cycle is shown, leading to abnormal cardiac metabolism and further processes like malic acid accumulation, oxidative stress, glycolysis, gluconeogenesis, hyperglycemia, AGEs formation, inflammation, atrial remodeling, and atrial fibrillation. Arrows indicate the progression between each stage.

The mechanism of action of DL-Malic acid and the TCA in the development of atrial fibrillation.

## Linked entities

- **Chemicals:** DL-Malic acid (PubChem CID 525), L-Threonine (PubChem CID 6288), L-Valine (PubChem CID 6287), L-Cysteine (PubChem CID 581)
- **Diseases:** atrial fibrillation (MONDO:0004981), hyperuricemia (MONDO:0002144)

## Full-text entities

- **Diseases:** HUA (MESH:D033461), AF (MESH:D001281)
- **Chemicals:** L-Valine (MESH:D014633), DL-Malic acid (MESH:C030298), L-Threonine (MESH:D013912), L-Cysteine (MESH:D003545)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

8 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12580274/full.md

## References

49 references — full list in the complete paper: https://tomesphere.com/paper/PMC12580274/full.md

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Source: https://tomesphere.com/paper/PMC12580274