Associations of Physical Activity With Mortality Across Cardiovascular–Kidney–Metabolic Syndrome Stages: Evidence From NHANES 1999 to 2018

Abstract

Background 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. Methods 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. Results 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. Conclusions 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.