Key Points

Cardiovascular–kidney–metabolic (CKM) syndrome stages 1–4 were associated with a graded risk of cardiovascular mortality in a nationally representative sample of US adults.Risk was similar between stages 0 and 1, suggesting that stage 1 represents a prime opportunity for prevention and risk mitigation.CKM staging is specific to cardiovascular mortality, given lack of a strong association with either noncardiovascular or cancer mortality.

Background

It is imperative to critically evaluate the prognostic implications of cardiovascular–kidney–metabolic (CKM) syndrome staging to inform clinical practice. The primary aims of this study were to define the risk of mortality associated with each CKM syndrome stage and to determine the corresponding restricted mean survival time over a 15-year period.

Methods

This was a longitudinal study of 50,678 community-dwelling US adults aged 20 years and older with baseline data for CKM stage determination participating in the 1999–2018 National Health and Nutrition Examination Survey. CKM stages were defined according to the American Heart Association presidential advisory. Fifteen-year adjusted cumulative incidences of cardiovascular mortality were calculated for each stage from confounder-adjusted survival curves using the G-formula.

Results

Over a median 9.5-year follow-up, 2564 participants experienced cardiovascular death. The 15-year adjusted cumulative incidences of cardiovascular mortality were stage 0, 5.5% (95% confidence interval [CI], 1.8 to 9.3); stage 1, 5.7% (95% CI, 3.2 to 8.2); stage 2, 7.9% (95% CI, 6.8 to 9.1); stage 3, 8.7% (95% CI, 6.7 to 10.8); and stage 4, 15.2% (95% CI, 13.6 to 16.8). The absolute risk difference between CKM stage 4 and stage 0 at 15 years was 9.6% (95% CI, 5.6 to 13.6). The survival difference between CKM stage 0 and stage 4 at 15 years was 8.1 (95% CI, 8.0 to 8.2) months.

Conclusions

Our findings reveal a graded risk of cardiovascular mortality associated with higher CKM syndrome stage.