BackgroundThe relationship between serum apolipoprotein A1 (APOA1) and atrial fibrillation (AF) is not known. Therefore, we sought to investigate the associations between APOA1 and AF in the Chinese population.MethodsThis case–control study included 950 patients with AF (29–83 years old, 50.42% male) who were hospitalized consecutively in China between January 2019 and September 2021. Controls with sinus rhythm and without AF were matched (1:1) to cases by sex and age. Pearson correlation analysis was performed to investigate the correlation between APOA1 and blood lipid profiles. Multivariate regression models were used to explore the association between APOA1 and AF. The receiver operator characteristic (ROC) curve was constructed to examine the performance of APOA1.ResultsMultivariate regression analysis showed that low serum APOA1 in men and women with AF was significantly associated with AF (OR = 0.261, 95% CI: 0.162–0.422,P< 0.001). Pearson correlation analysis indicated that serum APOA1 was positively correlated with total cholesterol (TC) (r= 0.456,p< 0.001), low-density lipoprotein cholesterol (LDL-C) (r= 0.825,p< 0.001), high-density lipoprotein cholesterol (HDL-C) (r= 0.238,p< 0.001), and apolipoprotein B (APOB) (r= 0.083,p= 0.011). ROC curve analysis showed that APOA1 levels of 1.105 g/L and 1.205 g/L were the optimal cut-off values for predicting AF in males and females, respectively.ConclusionLow APOA1 in male and female patients is significantly associated with AF in the Chinese population of non-statin users. APOA1 may be a potential biomarker for AF and contribute to the pathological progression of AF along with low blood lipid profiles. Potential mechanisms remain to be further explored.