Associations of Sitting Time and Leisure-Time Physical Activity with Mortality Across Cardiovascular–Kidney–Metabolic Syndrome Stages

Background: Cardiovascular–kidney–metabolic (CKM) syndrome confers mortality risk, but whether CKM severity modifies associations of sitting time and leisure-time physical activity (LTPA) with mortality is uncertain. Methods: We examined 15,444 adults aged 20–79 years in the National Health and Nutrition Examination Survey (2007–2018), linked to mortality records through 2019. Survey-weighted multivariable Cox proportional-hazards models were used to estimate hazard ratios (HRs) for all-cause and heart-disease mortality. Results: Over a median of 6.6 years, 1483 deaths occurred, including 354 heart-disease deaths. In survey-weighted multivariable Cox models, higher leisure-time physical activity was associated with lower all-cause and heart-disease mortality across CKM strata. Among participants with advanced CKM, sitting >8 versus ≤4 h/d was associated with higher all-cause mortality (HR, 2.09; 95% CI, 1.61–2.72) and heart-disease mortality (HR, 2.52; 95% CI, 1.62–3.94); however, formal interaction tests did not provide clear evidence of overall effect modification by CKM severity. Participants reporting <150 moderate-equivalent minutes of LTPA per week and >8 h of sitting per day had the largest point estimate for all-cause mortality relative to the reference group. Conclusions: These findings support the consideration of both sitting time and LTPA when assessing adults across the CKM spectrum.