Associations of Physical Activity With Mortality Across Cardiovascular-Kidney-Metabolic Syndrome Stages: Evidence...

Cardiovascular-kidney-metabolic (CKM) syndrome integrates cardiovascular, renal, and metabolic dysfunction and is associated with high mortality. Stage-stratified evidence linking physical activity (PA) to mortality remains limited.

We analyzed 19 930 adults with CKM stages 0 to 4 from the NHANES (National Health and Nutrition Examination Survey, 1999-2018), with mortality follow-up through 2019. PA was assessed by duration (minute/week) and volume (metabolic equivalent of task-min/week) across recreational, transport, and occupational domains. Survey-weighted Cox models with restricted cubic splines characterized dose-response associations, defined restricted cubic spline-derived reference ranges, and tested interactions.

During follow-up, 2759 deaths occurred (997 CKM related). Mortality increased sharply with CKM stage (all cause: 2.7% in CKM 0-1, 7.0% in CKM 2, and 33.5%-39.2% in CKM 3-4; CKM-related: <2% in CKM 0-2 and 14.2%-15.5% in CKM 3-4). Higher PA was associated with lower mortality across stages, with the largest absolute differences in CKM 3-4. Associations were nonlinear and L-shaped. In CKM 3-4, total PA near the reference range (≈500 min/week or ≈2000 metabolic equivalent of task-min/week) was associated with lower all-cause mortality (hazard ratio [HR], 0.745-0.700) and CKM-related mortality (HR, 0.739-0.690), whereas recreational PA (≈250 min/week or ≈1000 metabolic equivalent of task-min/week) showed the strongest inverse associations (all-cause HR, 0.740-0.702; CKM-related HR, 0.568-0.550). Occupational PA displayed a U-/J-shaped pattern. Interactions were strongest for renal dysfunction, particularly proteinuria.

Modest, attainable PA-especially recreational activity-was associated with lower all-cause and CKM-related mortality, with the greatest differences in CKM stages 3 to 4.