Abstract
BACKGROUND: Cardiovascular-Kidney-Metabolic (CKM) syndrome involves interconnected cardiovascular, renal, and metabolic conditions. The dose-response relationship between physical activity and bidirectional CKM stage transitions remains unclear. METHODS: Using data from the China Health and Retirement Longitudinal Study (CHARLS), cross-sectional analysis pooled 14,310 observations from 10,868 participants. Logistic regression with clustered robust standard errors accounted for intra-individual correlation. Longitudinal analysis (n = 3442) employed continuous-time multi-state Markov models with a 5-state structure (Stages 0-4). To evaluate physical activity effects, stages were regrouped into low-risk (Stages 0-2) and high-risk states (Stages 3-4) using a 2 × 2 transition intensity matrix. Physical activity was measured in MET-min/week and categorized into quartiles (Q1-Q4). RESULTS: Compared with Q1, Q2, Q3, and Q4 were associated with 43.1%, 52.5%, and 53.1% lower risk of high-risk CKM stages, respectively. RCS analysis demonstrated nonlinear dose-response relationships between physical activity and CKM stage progression. Subgroup analyses showed more pronounced protective effects in older adults and single individuals. During 4-year follow-up, 31.6% experienced progression and 6.8% showed improvement. Stage 4 acted as a complete absorbing state without any reversal. Transition intensity analysis revealed that transitions between adjacent stages were notably higher than cross-stage transitions. The Q4 physical activity level significantly reduced transitions from low-risk to high-risk states (HR = 0.598, 95% CI: 0.459-0.777) and promoted transitions from high-risk to low-risk states (HR = 2.995, 95% CI: 1.257-7.134). CONCLUSIONS: Moderate-to-high physical activity effectively reduces CKM progression risk and promotes improvement, providing evidence for CKM prevention and management.