Abstract 4361830: Onset of Arrhythmias in the CKM Continuum: Real-World Insights from a National Cohort

Introduction: The AHA Cardiovascular-Kidney-Metabolic (CKM) framework outlines a continuum of risk, starting with metabolic dysfunction and leading to major cardiovascular events. However, the role and timing of arrhythmia onset within this trajectory remain poorly understood, and the impact of major arrhythmias has not been reported. This real-world evidence (RWE) study is the first to examine arrhythmias onset across the CKM continuum, offering new insights with potential implications for earlier detection, risk stratification, and intervention. Methods: We conducted a retrospective real-world evidence study using the Symphony Integrated Dataverse (2018–2024) to analyze adults with obesity. Patients were stratified into two cohorts based on cardiovascular-kidney-metabolic (CKM) risk at baseline. Cohort A (Non-Arrhythmia) included individuals with obesity but without any prior CKM risk factors, while Cohort B (Arrhythmia) comprised patients with obesity and a documented history of arrhythmia, in the absence of other CKM risk factors. CKM progression was specifically analyzed within Cohort A (Fig 1). Key outcomes included the incidence of new-onset arrhythmias, time to progression across CKM stages, and the occurrence of major adverse cardiovascular events (MACE). Results: Cohort A included 3,382,510 patients, while Cohort B comprised 269,867 (Fig 2). In Cohort A, arrhythmia incidence increased with CKM progression, rising from 6.3% after Stage 1 to 9.3% after Stage 2 and 12.5% after Stage 3. When stratified by age, younger patients showed higher arrhythmia rates at earlier CKM stages, with 41% in those aged 18–34 after Stage 1, 44% in those 35–54 after Stage 2, and 42% in those over 65 after Stage 3 (Fig 3). In Cohort B, arrhythmia onset typically occurred four months before the obesity index date. In Cohort A, MACE events followed CKM progression rapidly, with a median of 65 days after Stage 3, and atrial fibrillation appeared at a median of 49 days post–Stage 3 (Fig 4). Conclusions: In this large RWE study, arrhythmia frequently emerged early in the CKM disease continuum. These findings highlight the potential value of incorporating arrhythmia surveillance into risk stratification for patients at risk of CKM progression. Further research is needed to determine whether early arrhythmia represents a modifiable inflection point on the path to major adverse cardiovascular events