Associations of cardiovascular–kidney–metabolic syndrome stages with long-term mortality among US cancer survivors: a prospective cohort study

INTRODUCTION: Cardiovascular-Kidney-Metabolic (CKM) syndrome is common among cancer survivors, largely driven by overlapping risk factors and therapy-induced toxicities; however, its contribution to long-term mortality has not been clarified. METHODS: From the 1999–2018 National Health and Nutrition Examination Survey (NHANES) cycles, 2,274 cancer survivors with CKM syndrome stages 1–4 were included. Associations between CKM syndrome staging and long-term mortality were analyzed using weighted Cox regression, and further explored through subgroup and sensitivity analyses. RESULTS: During a median follow-up of 10.2 years, 854 deaths occurred (277 cancer-related, 224 cardiovascular). Higher CKM stages were associated with increased all-cause and cardiovascular mortality, but not cancer-specific mortality. Adjusted HRs (95% CIs) for all-cause mortality were 1.215 (95% CI: 0.757–1.950) for stage 2, 1.772 (95% CI: 1.089–2.885) for stage 3, and 2.560 (95% CI: 1.597–4.103) for stage 4; for cardiovascular mortality, HRs were 1.406 (95% CI: 0.582–3.393), 2.910 (95% CI: 1.108–7.644), and 5.960 (95% CI: 2.158–16.458). CONCLUSION: Progression of CKM syndrome was linked to increased all-cause and cardiovascular mortality among cancer survivors, underscoring the need for early recognition and intervention. TRIAL REGISTRATION: Not applicable.