A metabolic-to-inflammatory pattern in cardiovascular-kidney-metabolic syndrome staging: a comparative...

Amid the cardiovascular-kidney-metabolic (CKM) syndrome public health crisis, this study aimed to explore differential pathological associations with established versus advanced CKM status and assess its consistency across Chinese and U.S. adults.

This cross-sectional study analyzed data from two independent sources: a community survey in Shaanxi, China (n=2, 100) and the U.S. National Health and Nutrition Examination Survey (NHANES) (2011-2018; n=5, 359). Associations between three pathological axes-visceral adiposity (VA), insulin resistance/dyslipidemia pathological score (IRD-PS), and systemic low-grade inflammation pathological score (SLI-PS)-and two key CKM outcomes (established: Stages 2-4 vs. 0-1; advanced: Stages 3-4 vs. 0-2) were evaluated using Firth's penalized logistic regression to address potential quasi-complete separation in the outcome data.

IRD-PS exhibited the strongest association with established CKM status in both populations (Shaanxi: OR = 2.49, 95% CI 2.18, 2.86; NHANES: OR = 2.52, 95% CI 2.24, 2.82). In contrast, SLI-PS was significantly and consistently correlated with advanced CKM status (Shaanxi: OR = 1.11, 95% CI 1.03, 1.19; NHANES: OR = 1.07, 95% CI 1.01, 1.14). Statistical exploratory decomposition analysis revealed IRD-PS largely attenuated the association between VA and established CKM status, statistically accounting for 67.1% of the effect in Shaanxi and 64.5% in NHANES. In the NHANES, significant racial/ethnic heterogeneity was observed in the IRD-PS-established CKM status association (P for interaction < 0.001), with the strongest association in non-Hispanic Asian people (OR = 3.96) and the weakest in non-Hispanic Black people (OR = 2.03). These cross-sectional associations should be interpreted with caution.

Our findings support a conceptual model of CKM syndrome in which metabolic dysregulation is the primary correlate of the established (Stage 2+) CKM status and in which systemic inflammation is a more prominent correlate of advanced (Stage 3+) CKM status. These findings may primarily generalize to the analyzed subsamples rather than broader general populations. Given the cross-sectional design, all findings are strictly hypothesis-generating, and the proposed stage-specific pathological pattern requires formal validation in future longitudinal cohorts.