Differential benefits of reallocating sedentary time to physical activity on atrial fibrillation across metabolic obesity phenotypes: a prospective cohort study

Background Current guidelines generally recommend “moving more and sitting less” but lack phenotype-specific recommendations for obese individuals. Objective We aimed to investigate the differential associations of guideline-recommended moderate-to-vigorous physical activity(MVPA) and reduced sedentary behavior(SB) with incident atrial fibrillation(AF) across metabolic obesity phenotypes. Methods We included 17,476 obese participants from UK Biobank wearing a wrist accelerometer for 7 days and without AF at baseline. Obesity was categorized into metabolically healthy(MHO) and unhealthy(MUHO). Cox models with measures of additive interaction were used to examine the independent and combined effects of metabolic status, MVPA and SB on AF. Isotemporal substitution models estimated the impact of reallocating SB to MVPA. Mediation analyses were performed to explore potential mediators. Results During a median follow-up of 8.09 years, 1092 participants developed AF. Significant benefit from guideline-recommended MVPA [HR=0.70(0.60,0.82), p<0.0001] and risk from prolonged SB(>11.2 hour/day) [HR=1.20(1.03,1.40), p=0.02] were observed in MUHO while no significant associations were found in MHO. Guideline-below MVPA and MUHO exhibited a significant additive interaction, with a relative excess risk(RERI) of 0.41 and proportion attributable to the interaction(AP) of 0.31. Reallocating 1 hour/day of SB to MVPA conferred significant AF risk reduction in MUHO individuals [HR=0.90(0.84, 0.96)], whereas no significant benefit was observed in the MHO phenotype [HR=0.96(0.87, 1.07)]. The mediated proportions of MVPA and SB with incident AF explained by metabolic factors and central obesity were 14.7% and 30.1%, respectively. Conclusions MUHO compared to MHO individuals derived significantly greater AF risk reduction from guideline-recommended MVPA and reduced sedentary time. Our finding supports that targeting SB replacement with MVPA is a compelling strategy for MUHO individuals to attenuate AF risk. For MHO individuals, maintaining a healthy lifestyle might be crucial to prevent the transition to an unhealthy phenotype.