Association between cardio-kidney-metabolic syndrome and early or very early onset atrial fibrillation.

Introduction: Early onset atrial fibrillation (AF), occurring at younger ages, is understudied. The Cardiovascular-Kidney-Metabolic (CKM) syndrome highlights the interplay between cardiovascular disease (CVD), chronic kidney disease (CKD), and metabolic syndrome. We aimed to explore the longitudinal association between CKM and its components and early onset AF. Methods: We used data from the All of Us Research Program, including participants ≤65 years of age with linked electronic health records (EHR), evaluating presence of individual CKM components (including obesity, obstructive sleep apnea, diabetes, CKD, hypertension, and heart failure), and AF status. In those without baseline AF, incident AF was ascertained using the EHR. We calculated the prevalence and incidence rate of AF by CKM status and used Cox Proportional Hazard models to explore the multivariable-adjusted associations between CKM and AF across the different baseline age strata: ≤65 years (early onset) and ≤45 years (very early onset). Results: A total of 296,428 individuals were included. Mean age was 44.9 years, 63.5% were female, 41.8% were White. The prevalence of baseline AF was significantly higher for participants with CKM compared to those without. During follow-up, CKM was associated with increased risk for AF across all age groups. The risk for AF was increased across all components of CKM, with results most pronounced in participants ≤45. The addition of CKM components improved prediction of incident AF beyond the basic model. Conclusion: Our findings reveal an association between CKM and both early and very early onset AF. The particularly strong associations in the youngest adults points to need for early intervention on CKM syndrome to potentially reduce very early onset AF.