Accelerometer-derived “weekend warrior” physical activity pattern and trajectory of cardio-renal-metabolic multimorbidity: a multi-state analysis in the UK Biobank

Cardio-renal–metabolic multimorbidity (CRMM), defined as the coexistence of at least two of cardiovascular disease (CVD), type 2 diabetes (T2D), and chronic kidney disease (CKD), poses a major public health challenge. Moderate-to-vigorous physical activity (MVPA) may reduce the risk of these individual diseases, yet studies examining its association with longitudinal disease progression are lacking. We analyzed 76,875 UK Biobank participants with valid 7-day wrist-worn accelerometer data (2013–2015). MVPA patterns were categorized as inactive, regularly active, or weekend warrior (WW). Multi-state models were used to characterize longitudinal transitions from a healthy state to first cardio-renal-metabolic disease (FCRMD), subsequent progression to CRMM, and all-cause mortality. Fully adjusted Cox and multi-state models estimated effect sizes, with subgroup and sensitivity analyses assessing robustness. Over a median follow-up of 8.1 years, 8,495 participants developed FCRMD, 934 progressed to CRMM, and 2,373 died. Compared with inactive participants, regularly active (HR = 0.82, 95% CI: 0.77–0.87) and WW (HR = 0.83, 95% CI: 0.79–0.87) had lower risks of transitioning from healthy to FCRMD and from FCRMD to CRMM (regularly active: HR = 0.75, 95% CI: 0.62–0.91; WW: HR = 0.81, 95% CI: 0.69–0.94), with reduced mortality across other transitions except CRMM-to-death. Protective effects were stronger among women for the transition to FCRMD and among participants without hypertension during subsequent disease progression. Subgroup and sensitivity analyses confirmed robustness. Both regularly active and weekend warrior patterns of baseline MVPA were associated with lower risks of CRMD onset and progression, particularly during the early stages, underscoring the public health value of MVPA and the importance of early intervention for precision prevention.