Abstract Body (Do not enter title and authors here): Background:
Cardiorenal-metabolic multimorbidity (CRMM), defined by the co-occurrence of cardiovascular disease (CVD), chronic kidney disease (CKD), and type 2 diabetes (T2D), poses a growing global public health challenge. This study evaluates the preventive role of physical activity (PA) in delaying or mitigating progression from a healthy state to the first CRMD (FCRMD), then to CRMM, and ultimately to death.
Methods:
We conducted a prospective cohort study using data from the UK Biobank. All participants were free of CRMDs (CVD, T2D, CKD) at baseline. The accelerometer-based cohort included 73,952 individuals with 7-day wrist-worn accelerometer data (2013–2015), from which durations of light (LPA), moderate (MPA), and vigorous (VPA) PA were derived. The questionnaire-based cohort included 328,147 participants who completed the International Physical Activity Questionnaire (IPAQ) between 2006 and 2010, with PA classified by domain (leisure, work, household, transport). Multistate models were used to assess the association between PA and disease progression.
Results:
In the accelerometer cohort (median follow-up 7.0 years), 7,303 participants developed FCRMD, 868 progressed to CRMM, and 1,975 died. Greater VPA and MPA duration were associated with reduced risk of progression. Compared to the lowest quartile (Q1), VPA showed the strongest protective effect for transitions from healthy to FCRMD (HR 0.69, 95% CI 0.64–0.74), FCRMD to CRMM (0.66, 0.52–0.84), and health to death (0.47, 0.39–0.56). MPA was most protective for mortality risk from FCRMD (0.53, 0.40–0.71). When we further considered the disease-specific transitions, we found VPA and MPA play similar roles in transitions starting with health and from CVD status to death. LPA was beneficial only for transitions from health to CKD (0.67, 0.55–0.83) and health to death (0.73, 0.62–0.86). In the questionnaire cohort, high PA was protective for most transitions, except from CKD and T2D to CRMM.
Conclusion:
Engaging in multiple types of PA and higher levels of MPA and VPA were associated with lower risks of CRMD onset, progression to multimorbidity, and death. These findings underscore the preventive role of physical activity in mitigating the burden of cardio-renal-metabolic multimorbidity.