Bidirectional transitions of cardiovascular-kidney-metabolic syndrome states in middle-aged and older adults: evidence from a nationwide cohort study

Abstract Background Cardiovascular–Kidney–Metabolic (CKM) syndrome is a systemic condition from the interplay among metabolic risk factors, chronic kidney disease (CKD), and cardiovascular system. This study aimed to characterize bidirectional transition patterns between CKM states and identify their determinants. Methods and results We included community-dwelling adults ≥45 years from national China Health and Retirement Longitudinal Study (CHARLS), with CKM state assessments in 2011 and 2015. Multi-state Markov models (MSM) estimated transition intensities/probabilities among non-CKM (stage 0), light CKM (stages 1,2), advanced CKM (stages 3,4), death, and factors for transitions.A total of 6,388 participants were analyzed (53.80% female; mean age 59.41±9.02 years; mean follow-up 3.86±0.51 years). Baseline: 412 (6.45%) non-CKM, 4,605 (72.09%) light CKM, 1,371 (21.46%) advanced CKM. Follow-up: 1,675 transitions (1,077 progressing, 171 regressing, 427 death). Four-year probabilities: non-CKM→light CKM (70.5%); light CKM→non-CKM (2.7%), light CKM→advanced CKM (16.7%); advanced CKM→light CKM (3.4%), advanced CKM→death (15.0%). Age, sex, urban/rural residence, activities of daily living (ADL), depressive symptoms were key determinants. Conclusion This national cohort delineated CKM state bidirectional transitions, revealed progression-regression asymmetry and state-specific determinants, providing evidence for prevention-oriented, risk-stratified CKM management in middle-aged/older adults.