# Physical Activity and Bidirectional Stage Transitions in Cardiovascular-Kidney-Metabolic Syndrome: A Cohort Study

## TL;DR

This study shows that higher physical activity reduces the risk of progressing to severe cardiovascular-kidney-metabolic syndrome and can even help reverse it in some cases.

## Contribution

The study provides new evidence on the bidirectional effects of physical activity on CKM syndrome stage transitions using a multi-state Markov model.

## Key findings

- Higher physical activity levels are associated with significantly lower risk of transitioning to high-risk CKM stages.
- Moderate-to-high physical activity promotes transitions from high-risk to low-risk CKM states.
- Stage 4 CKM is an absorbing state with no observed reversal during the 4-year follow-up.

## 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.