Background & aims: Some omega 3 polyunsaturated fatty acids (PUFAs) are said to demonstrate a dose-related risk of atrial fibrillation (AF), conversely, some omega 6 PUFAs might have AF protective potential. However, few investigated the relation among ischemic strokes. Primarily, we aimed to examine a relation between omega 3 and omega 6 PUFAs and the presence of AF in ischemic strokes. Further, since, some PUFAs are said to affect the cardiac load, we secondarily aimed to investigate the association between omega 3 and omega 6 PUFAs and brain natriuretic peptide (BNP) and the occurrence of cerebral large vessel occlusion (LVO) in ischemic strokes with AF. Methods: Consecutive patients with ischemic stroke admitted between 2012 and 2022 were retrospectively screened. Plasma levels of PUFAs, including eicosapentaenoic acid (EPA), docosahexaenoic acid, dihomo-gamma-linolenic acid (DGLA) and arachidonic acid (AA), were assayed. Data were analyzed using a Poisson regression analysis with a robust variance estimator and a multiple linear regression analysis. Results: We screened 2112 consecutive ischemic strokes, including 1574 (1119 [71%] males, median age 69 years). Lower DGLA (prevalence ratio (PR) 0.885, 95% CI 0.811-0.966, p = 0.006), lower AA (PR 0.797, 95% CI 0.649-0.978, p = 0.030), and higher EPA/AA ratio (PR 1.353, 95% CI 1.036-1.767, p = 0.026) were associated with AF. Checking the linearity between AF and PUFAs, negative linear trends were observed between DGLA quartiles (Q1: PR 1.901, Q2: PR 1.550, Q3: PR 1.423, Q4: 1.000, p < 0.001 for trend) and AA quartiles (Q1: PR 1.499, Q2: PR 1.204, Q3: PR 1.125, Q4: 1.000, p = 0.004 for trend), with positive linear trends between EPA/AA ratio quartiles (Q1: 1.000, Q2: PR 1.555, Q3: PR 1.612, Q4: PR 1.797, p = 0.001 for trend). Among patients with AF, a negative association between AA and BNP (unstandardized coefficient -1.316, 95% CI -2.290 similar to-0.342, p = 0.008) was observed, and lower AA was associated with LVO (PR 0.707, 95% CI 0.527-0.950, p = 0.021). Conclusion: Lower DGLA and AA and a higher EPA/AA ratio might be related to the development of AF in ischemic strokes. Further, AA might have a cardio-cerebrovascular protective role in ischemic strokes with AF. (c) 2024 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights are reserved, including those for text and data mining, AI training, and similar technologies.