Introduction: The effect of T lymphocytes on atrial fibrillation (AF) is still unclear. We aimed to assess the associations between the T-lymphocyte subgroup distribution and incident AF and AF prognosis. Methods: Consecutive patients were enrolled from June 2020 to October 2021. Their T-cell subgroups, including CD3, CD4, and CD8 T cells, and the CD4/CD8 ratio (CDR) were measured. We assessed the relationships between the CDR and composite endpoints, including hospitalization due to heart failure, stroke or systemic embolism, and cardiovascular mortality rates. Results: A total of 45,905 patients, among whom 818 had AF, were enrolled. The proportions of the T-lymphocyte subgroups CD3 (OR: 0.9995; 95% CI: 0.9993–0.9997, p < 0.001), CD4 (OR: 0.9995; 95% CI: 0.9991–0.9998, p = 0.004), and CD8 (OR: 0.9988; 95% CI: 0.9984–0.9992, p < 0.001) and the CDR (OR: 1.2714; 95% CI: 1.1355–1.4165, p < 0.001) were correlated with AF incidence. The CDR was associated with AF incidence (OR: 1.1998; 95% CI: 1.0746–1.3336, p < 0.001) after adjustment. High CDR was associated with a higher rate of hospitalization due to heart failure (HR: 3.45; 95% CI: 1.71–6.96, p < 0.001), stroke, or systemic embolism (HR: 2.54; 95% CI: 1.32–4.91, p = 0.005), and cardiovascular mortality (HR: 2.25; 95% CI: 1.05–4.84, p = 0.038). There was no significant difference in all-cause mortality between CDR strata (HR: 1.61; 95% CI: 0.90–2.87, p = 0.111). Conclusion: Elevated CDR was positively associated with the incidence and prognosis of AF. This finding may help improve the prevention and treatment of AF.
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