A metabolic-to-inflammatory pattern in cardiovascular-kidney-metabolic syndrome staging: a comparative cross-sectional study

Background: 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. Methods: 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. Results: = 2.03). These cross-sectional associations should be interpreted with caution. Conclusions: 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.