The role of circulating polyunsaturated fatty acids in atrial fibrillation and atrial cardiomyopathy a machine learning-informed structural modelling approach

Q: What are the key findings of this study?

PUFA supplementation was associated with lower atrial fibrillation prevalence (β=-0.096; 95% CI -0.145 to -0.047; P<0.001), though higher circulating DHA was associated with higher AF incidence.

Q: What is the clinical evidence from this study?

Study design: Observational. Population: Atrial fibrillation (n=483372). Intervention: PUFA supplementation and circulating PUFA profiles vs. No supplementation or lower circulating PUFA levels. Primary outcome: Atrial fibrillation prevalence (associated with PUFA supplementation) (β -0.096, 95% CI -0.145 to -0.047, p=<0.001).

Q: What does this research mean for the field?

PUFA supplementation is associated with lower atrial fibrillation prevalence, while higher circulating omega-3 and omega-6 are linked to lower AF incidence, despite higher circulating DHA associating with increased AF incidence. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

Q: What question did this study set out to answer?

Investigate the associations of circulating polyunsaturated fatty acid profiles and supplementation with the prevalence and incidence of atrial fibrillation and atrial cardiomyopathy.

Jakob Versnjak; Giuseppe Trimarchi; Anna Foryst‐Ludwig; Benjamin Wild; Kilian Kuehne; Gabriele G. Schiattarella; Michael Gotthardt; Roland Eils; Titus Kühne; Ulrich Kintscher; Marcus Kelm

doi:10.1093/ejhf/xuag238

July 25, 2026European Journal of Heart Failure

The role of circulating polyunsaturated fatty acids in atrial fibrillation and atrial cardiomyopathy a machine learning-informed structural modelling approach

View Full Paper

Ask AI

Bookmark

Share

Key result

PUFA supplementation is linked to lower AF prevalence, despite circulating DHA correlating with higher incidence.

β -0.096
95% CI -0.145 to -0.047
P<0.001
n=483,372

Why the study?

The associations of circulating polyunsaturated fatty acids and PUFA supplementation with atrial fibrillation prevalence and incidence, especially in patients predisposed to AF including those with HFpEF, were unclear.

Are circulating polyunsaturated fatty acid profiles and PUFA supplementation associated with the prevalence and incidence of atrial fibrillation?

Key Points

Investigate the associations of circulating polyunsaturated fatty acid profiles and supplementation with the prevalence and incidence of atrial fibrillation and atrial cardiomyopathy.
Analyzed 483,372 individuals from the UK Biobank (8,503 prevalent and 32,671 incident atrial fibrillation cases) utilizing nuclear magnetic resonance metabolomics.
Integrated systematic deconfounding with an explainable supervised classifier and generalized structural equation modeling.
Higher circulating ω-6 (β = -0.083, 95% CI -0.097 to -0.069; p < 0.001) and ω-3 concentrations (β = -0.093, 95% CI -0.122 to -0.065; p < 0.001) were associated with lower atrial fibrillation incidence, whereas higher DHA was associated with higher incidence (β = 0.058, 95% CI 0.031 to 0.085; p < 0.001).
Polyunsaturated fatty acid supplementation was associated with higher circulating levels and lower atrial fibrillation prevalence (β = -0.096, 95% CI -0.145 to -0.047; p < 0.001), demonstrating the strongest associations among cholesterol-lowering medication users and women.

Study Design

Type

Observational (n=483,372)

Multicenter

Yes

Structured PICO

Are circulating polyunsaturated fatty acid profiles and PUFA supplementation associated with the prevalence and incidence of atrial fibrillation?

P

Population

483,372 individuals from the UK Biobank analyzed for associations between circulating polyunsaturated fatty acid profiles, PUFA supplementation, and atrial fibrillation prevalence and incidence.

E

Exposure

Higher circulating polyunsaturated fatty acid (PUFA) profiles and self-reported PUFA supplementation

C

Comparator

Lower circulating PUFA levels and non-supplementation

O

Outcome

Atrial fibrillation (AF) prevalence and incidencehard clinical

Main Result

Effect estimate: β -0.096 (95% CI -0.145 to -0.047)

p-value: p=<0.001

Implication

Circulating ω-3 and ω-6 PUFAs are associated with lower AF incidence, while DHA is associated with higher AF incidence, highlighting the need for careful evaluation of specific PUFA formulations.

Abstract

AIMS: Beyond their cardioprotective effects, polyunsaturated fatty acids (PUFAs) have also been linked to arrhythmogenicity, raising concern among individuals predisposed to atrial fibrillation (AF), including patients with heart failure with preserved ejection fraction (HFpEF). Here, we examined associations of circulating PUFA profiles and PUFA supplementation with AF prevalence and incidence. METHODS AND RESULTS: We analysed 483,372 individuals from the UK Biobank (8,503 prevalent AF; 32,671 incident AF) with nuclear magnetic resonance (NMR) metabolomics, combining systematic deconfounding, an explainable supervised classifier and generalised structural equation modelling (GSEM).Anthropometric, demographic and genetic risk factors were stronger correlates of AF prevalence and incidence than lipidomic profiles. NMR analysis indicated lower plasma PUFA concentrations in AF, atrial cardiomyopathy (AtCM) and in HFpEF, most pronounced with cholesterol-lowering medication (CLM) use and partially attenuated in participants reporting PUFA supplementation. Higher ω-6 concentrations were associated with lower AF prevalence and incidence; for AF incidence, β=-0.083 (95% CI -0.097 to -0.069; p<0.001), higher ω-3 with lower AF incidence (β=-0.093, 95% CI -0.122 to -0.065; p<0.001), and higher DHA with higher incidence (β=0.058, 95% CI 0.031 to 0.085; p<0.001), an association not evident in women. Supplementation was associated with higher circulating PUFAs and lower AF prevalence (β=-0.096, 95% CI -0.145 to -0.047; p<0.001), strongest among CLM users and women. Subgroup findings in HFpEF were directionally similar. CONCLUSIONS: Circulating PUFAs were lower in AF, AtCM and HFpEF. Lipid profiles indicated favourable associations for circulating ω-3 and ω-6, with a modest adverse signal for DHA. After adjustment for established risk factors, PUFA supplementation was associated with lower AF prevalence, including in patients with CLM and those with HFpEF. Formulations that substantially increase plasma DHA levels warrant careful evaluation given the observed association with AF incidence.

Discussion

No takes yet. Share an insight, caveat, or question.

Cite This Study

Versnjak et al. (2026) conducted an observational in Atrial fibrillation (n=483,372). PUFA supplementation and circulating PUFA profiles vs. No supplementation or lower circulating PUFA levels was evaluated on Atrial fibrillation prevalence (associated with PUFA supplementation) (β -0.096, 95% CI -0.145 to -0.047, p=<0.001). PUFA supplementation was associated with lower atrial fibrillation prevalence (β=-0.096; 95% CI -0.145 to -0.047; P<0.001), though higher circulating DHA was associated with higher AF incidence.

synapsesocial.com/papers/6ad0fc513afa093ea9acfd2e https://doi.org/10.1093/ejhf/xuag238