Long-term clinical outcome and risk stratification across stages of cardiovascular-kidney-metabolic syndrome in a nationwide cohort

Background/Aims: Cardiovascular-kidney-metabolic (CKM) syndrome is a continuum of metabolic, cardiovascular, and kidney dysfunctions. This study aimed to evaluate the association between CKM stages and the risk of adverse composite clinical outcomes. Methods: This retrospective cohort study used data from the Korean National Health Insurance Database and included 1,497,913 individuals who underwent at least two health checkups between 2009 and 2012. The participants were classified into CKM stages (0–4), and the primary outcome was a composite of all-cause death, myocardial infarction, ischemic stroke, hemorrhagic stroke, and hospitalization for heart failure. Results: The distribution of CKM stages was 17.4% (stage 0), 15.7% (stage 1), 57.6% (stage 2), 6.3% (stage 3), and 3.1% (stage 4). The incidence rate of primary outcomes increased progressively across the 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 with stage 0, the adjusted hazard ratios (HRs) for the primary outcome were significantly elevated: stage 1 (HR 1.09; 95% confidence interval [CI] 1.06–1.13; p < 0.001), stage 2 (HR 1.36; 95% CI 1.32–1.39; p < 0.001), stage 3 (HR 1.72; 95% CI 1.67–1.77; p < 0.001), and stage 4 (HR 2.70; 95% CI 2.62–2.79; p < 0.001). Conclusions: A higher CKM stage was associated with a progressive increase in the risk of all-cause mortality and major cardiovascular events. Clinicians may benefit from prioritizing the early identification of high-risk individuals and implementing targeted management strategies based on CKM staging to improve long-term adverse outcomes.