Cumulative Incidence of Mortality Associated with Cardiovascular-Kidney-Metabolic Syndrome

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 paper 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 is a longitudinal study of 50,678 community-dwelling U.S. adults aged 20 and older with baseline data for CKM stage determination participating in the 1999-2018 National Health and Nutrition Examination Survey. CKM stages defined according to the American Heart Association presidential advisory. 15-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, 2,564 participants experienced cardiovascular death. The 15-year adjusted cumulative incidences of cardiovascular mortality were: Stage 0, 5.5% (95% CI, 1.8-9.3); Stage 1, 5.7% (95% CI, 3.2-8.2); Stage 2, 7.9% (95% CI, 6.8-9.1); Stage 3, 8.7% (95% CI 6.7-10.8); Stage 4, 15.2% (95% CI, 13.6-16.8). The absolute risk difference between CKM Stage 4 and Stage 0 at 15 years was 9.6% (95% CI, 5.6-13.6). The survival difference between CKM stage 0 and Stage 4 at 15 years was 5.6 (95% CI, 5.5-5.7 months. Conclusions: Our findings reveal a graded risk for cardiovascular mortality associated with higher CKM syndrome stage.