Cardiac Electro-structural Remodeling and Arrhythmia Risks Across the Spectrum of Obesity Defined by the New Lancet framework

Abstract Background Obesity is linked to higher arrhythmia risk, yet BMI overlooks its complexity. Recently, the Lancet Commission has introduced a new obesity framework. We aimed to compare arrhythmia risks across distinct obesity categories. Methods Participants from the UK Biobank were stratified by obesity phenotypes. Co-primary outcomes included incident supraventricular, brady-, or ventricular arrhythmias, with secondary outcomes defined as their components. Obesity phenotypes were defined using five anthropometric measures, alongside ICD-10 codes, laboratory measurements, and self-reported data to ascertain organ dysfunction. Results Of 487,806 included individuals, 36.6%, 18.7%, and 44.7% were identified with non-obesity, preclinical obesity, and clinical obesity, respectively. Compared to non-obesity without organ dysfunction, clinical obesity was associated with significantly increased risk for all primary and secondary outcomes (all FDR-corrected P < 0.05), as well as arrhythmia recurrence risk. Preclinical obesity was associated with significantly elevated risk of SVA and bradyarrhythmia, but not for VA or arrhythmia recurrence. Clinical obesity exhibited significant ECG alterations, including prolonged P wave duration, PR interval, QTc interval, QRS duration, accompanied by shortened PP interval, elevated ventricular rate, as well as altered P-wave, R-wave, and T-wave axis. For structural remodeling, clinical obesity was associated with enlarged left atrial volume and concentric left ventricular (LV) remodeling. A similar but less pronounced pattern of electrical and structural remodeling was observed for preclinical obesity. Compared to BMI, the Lancet classification's incremental prognostic value was small, mixed, and outcome-dependent. Conclusions These findings reveal a gradient of arrhythmic and remodeling risk across obesity stages, underscoring the need for early monitoring in preclinical obesity and targeted intervention in clinical obesity to prevent cardiovascular complications.