LONG-TERM CLINICAL OUTCOME ACROSS STAGES OF CARDIOVASCULAR-KIDNEY-METABOLIC SYNDROME

Objective: Cardiovascular-kidney-metabolic (CKM) syndrome has a continuum of metabolic, cardiovascular, and kidney dysfunction and represents critical conditions significantly contributing to global morbidity and mortality, emphasizing the importance of accurate risk stratification. The effect of CKM staging on long-term clinical outcomes, including mortality and major cardiovascular events, remains unclear. This study aimed to evaluate the association between CKM stages and the risk of adverse composite clinical outcomes. Design and method: This retrospective cohort study utilized data from the Korean National Health Insurance Database, including 1,497,913 individuals who underwent at least two health checkups between 2009 and 2012. Based on predefined clinical criteria, participants were classified into CKM stages (0–4). The primary outcome was a composite of all-cause death, myocardial infarction, ischemic stroke, hemorrhagic stroke, and hospitalization for heart failure. Cox proportional hazard models were employed to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the composite outcome across CKM stages. Results: The incidence rate of composite outcomes increased progressively across CKM stages, from 2.07 per 1,000 person-years in stage 0 to 40.70 per 1,000 person-years in stage 4. Compared to stage 0, adjusted HRs for the composite outcome were significantly elevated: stage 1 (HR 1.091; 95% CI 1.057–1.126; p < .0001), stage 2 (HR 1.357; 95% CI 1.322–1.394; p < .0001), stage 3 (HR 1.720; 95% CI 1.668–1.773; p < .0001), and stage 4 (HR 2.699; 95% CI 2.615–2.786; p < .0001). CKM stage was a strong independent predictor of adverse clinical outcomes. The Kaplan-Meier curve demonstrated a clear separation in event-free survival among CKM stages, highlighting a stepwise increase in risk with higher stages. Conclusions: Higher CKM stages were associated with a stepwise increase in the risk of all-cause mortality and major cardiovascular events. Clinical efforts should focus on early identification and targeted management of individuals at higher CKM stages to mitigate the long-term burden of adverse outcomes.