Association Between Plasma Omega-3 and Omega-6 Fatty Acid Levels and Atrial Fibrillation: A Large-Scale, Real-World Retrospective Study in Japan

AIM: The relationship between omega-3 and omega-6 polyunsaturated fatty acids (PUFAs) and atrial fibrillation (AF) remains unclear. This retrospective study aimed to investigate the association between plasma levels of omega-3 PUFAs (eicosapentaenoic acid [EPA], docosahexaenoic acid [DHA]) and omega-6 PUFAs (arachidonic acid [AA] and dihomo-γ-linolenic acid [DGLA]) and the prevalence of AF. METHODS: After excluding patients who were prescribed icosapent ethyl (IPE) or were younger than 40 years, data from 9,178 patients at Juntendo University Hospital with plasma EPA, DHA, AA, and DGLA measurements obtained between April 2017 and January 2021 were analyzed. The plasma PUFA levels were divided into quartiles, with the lowest quartile used as the reference. Multivariable logistic regression and restricted cubic spline analyses were performed to assess the association between the PUFA levels and AF. RESULTS: The median age was 69 years (interquartile range [IQR], 59-77 years), and 60.6% of the participants were male. AF was diagnosed in 908 (9.9%) patients. After adjusting for age, sex, and body mass index (BMI), higher plasma levels of EPA, DHA, EPA+DHA, AA, and DGLA were significantly associated with a lower risk of AF (all P＜0.001). In contrast, no significant associations were observed between the PUFA ratios, including (EPA+DHA)/AA, EPA/AA, DHA/AA, and DGLA/AA, and AF. Restricted cubic spline analyses revealed linear inverse associations for EPA, DHA, EPA+DHA, and AA and AF, whereas a nonlinear association for DGLA and AF was observed. CONCLUSION: Within the physiological ranges, higher plasma levels of EPA, DHA, EPA+DHA, AA, and DGLA were independently and inversely associated with AF risk. However, extremely high EPA concentrations, achieved through pharmacological interventions, have been suggested to be associated with an increased risk of AF.