Abstract
BACKGROUND: The cardiovascular-kidney-metabolic (CKM) syndrome, introduced by the American Heart Association, underscores the interplay among metabolic, renal, and cardiovascular dysfunctions. OBJECTIVES: This study aimed to evaluate the prevalence and mortality risk across CKM syndrome stages in the UK population. METHODS: This prospective cohort study included 110,933 participants from the UK Biobank. The primary outcome was all-cause mortality, with cardiovascular disease (CVD)-specific mortality as a secondary outcome. Kaplan-Meier and Cox proportional hazards models were used to estimate survival and mortality risks. RESULTS: Among the 110,933 participants, 9.16% were classified as CKM stage 0, 13.53% as stage 1, 44.15% as stage 2, 26.25% as stage 3, and 6.91% as stage 4. Over a median follow-up of 14.7 years, 13,012 all-cause deaths and 1,613 CVD-specific deaths were recorded. All-cause mortality rates increased progressively across CKM stages: 6.32% (stage 0), 7.47% (stage 1), 10.12% (stage 2), 13.67% (stage 3), and 30.09% (stage 4). Similarly, CVD-specific mortality rates increased from 0.43% to 5.43%. Compared to stage 0, the adjusted HRs for all-cause mortality were 1.14 for stage 2, 1.25 for stage 3, and 2.13 for stage 4. For CVD-specific mortality, the adjusted HRs were 1.48 for stage 2, 1.99 for stage 3, and 3.46 for stage 4. CONCLUSIONS: Nearly 80% of individuals were classified into poor CKM stages (stages 2-4), which were strongly associated with significantly elevated risks of both all-cause and CVD-specific mortality. These findings emphasize the urgent need for early detection and targeted interventions in high-risk cardiometabolic populations.