Higher CKM syndrome stages were associated with increased all-cause mortality risk; stage 4 had a 4.77-fold higher risk compared to stage 0 in U.S. adults over median 7.25 years.
Cross-Sectional (n=38,397)
Yes
Does advanced Cardiovascular-Kidney-Metabolic (CKM) syndrome stage increase the risk of all-cause mortality in U.S. adults?
Higher stages of Cardiovascular-Kidney-Metabolic (CKM) syndrome are progressively associated with a significantly increased risk of all-cause mortality in U.S. adults.
Effect estimate: HR 1.05 (stage 1), HR 1.98 (stage 2), HR 3.09 (stage 3), HR 4.77 (stage 4) compared to stage 0 (95% CI 95% CI: stage 1 (0.81–1.44), stage 2 (1.54–2.56), stage 3 (2.36–4.06), stage 4 (3.47–5.76))
p-value: p=<0.001
Cardiovascular-Kidney-Metabolic (CKM) syndrome became the leading cause of death among U.S. adults in 2021. However, the relationship between different stages of CKM and the risk of all-cause mortality in the U.S. population remains unclear. Data from NHANES 2005–2018 and the Public-use Linked Mortality Files (LMF) were utilized in this study. Kaplan–Meier survival curves were generated to estimate survival probabilities across five CKM stages (stages 0 to 4) and compared using the log-rank test. Hazard ratio (HR) and 95% confidence interval (95%CI) for all-cause mortality were estimated using Cox proportional hazards regression models. Stratified analyses were conducted to explore potential effect modifications by age, sex, education, smoking status, drinking status and the Poverty Income Ratio (PIR). A total of 4,376 all-cause deaths were recorded during a median follow-up period of 7.25 years (IQR: 6.92–7.67). The risk of all-cause mortality increased progressively with higher CKM syndrome stages (P < 0.001). After multivariate adjustment, the risk of all-cause mortality for CKM stages 1 through 4 was 1.05 (95% CI: 0.81–1.44), 1.98 (95% CI: 1.54–2.56), 3.09 (95% CI: 2.36–4.06), and 4.47 (95% CI: 3.47–5.76) times higher than that for CKM stage 0, respectively. Additionally, subgroup analyses revealed that the risk of all-cause mortality in CKM stage 4 was higher among individuals under 60 years of age, females, current smokers, current drinkers, those with less than a high school education, and those with a household poverty index below1.3. Studies have found that populations with more advanced CKM staging have a higher risk of all-cause mortality. These findings underscore the need for targeted public health strategies to reduce mortality risk associated with CKM syndrome.
Du et al. (2026) conducted a cross-sectional in U.S. adults aged 20 years and older with varying stages of Cardiovascular-Kidney-Metabolic (CKM) syndrome (n=38,397). CKM syndrome stage classification (stages 0 to 4) vs. CKM stage 0 (reference) was evaluated on All-cause mortality (HR 1.05 (stage 1), HR 1.98 (stage 2), HR 3.09 (stage 3), HR 4.77 (stage 4) compared to stage 0, 95% CI 95% CI: stage 1 (0.81–1.44), stage 2 (1.54–2.56), stage 3 (2.36–4.06), stage 4 (3.47–5.76), p=<0.001). Higher CKM syndrome stages were associated with increased all-cause mortality risk; stage 4 had a 4.77-fold higher risk compared to stage 0 in U.S. adults over median 7.25 years.