Across 91,873 adults in the UK Biobank and US REGARDS cohorts tracked by accelerometry, replacing 30 minutes of daily sedentary behavior with moderate-to-vigorous physical activity (MVPA) was associated with a 20% lower odds of incident atrial fibrillation in REGARDS (OR 0.80, 95% CI 0.63–1.01), though the UK Biobank's larger sample showed only marginal, statistically null reductions after full adjustment (HR 1.00, 95% CI 0.99–1.02). Benefits appeared strongest in REGARDS participants aged 65 or older and those sleeping fewer than seven hours nightly. Swapping sedentary time for light activity or sleep showed little meaningful effect.
Atrial fibrillation is the world's most common sustained cardiac arrhythmia and a leading driver of stroke and heart failure, making modifiable risk factors genuinely consequential. The isotemporal substitution design — statistically reallocating fixed time budgets — is methodologically sound for disentangling sitting from activity. The divergence between cohorts is notable: REGARDS skews older, more diverse racially, and uses self-reported sleep, which may explain its stronger signal. The UK Biobank's null fully-adjusted result could reflect its younger, nearly all-White sample or greater covariate control. Both studies are observational; reverse causation cannot be ruled out. The benefit among poor sleepers suggests synergistic cardiovascular risk pathways worth investigating. As a preprint not yet peer-reviewed, these findings should be treated as preliminary — effect estimates and conclusions may shift after expert scrutiny. Still, the consistent directional message reinforces current physical activity guidelines for heart health.