Prevalence and Mortality Association of Different Stages of Cardiovascular-Kidney-Metabolic Syndrome

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.