Joint association of the inflammatory marker and cardiovascular-kidney-metabolic syndrome stages with all-cause and cardiovascular disease mortality: a national prospective study.

Background: Cardiovascular-kidney-metabolic (CKM) syndrome and systemic inflammation significantly contribute to mortality. However, the joint associations of CKM stages and systemic inflammation with all-cause and cardiovascular disease (CVD) mortality remain unclear. This study aimed to evaluate the independent and joint associations of CKM stages and systemic inflammation with all-cause and CVD mortality in a representative cohort of United States adults.

Methods: We analyzed data from 29,459 adults aged ≥ 20 years from the National Health and Nutrition Examination Survey (1999-2018). CKM stages were classified based on metabolic risk factors, CVD, and chronic kidney disease. Systemic inflammation was assessed using multiple indicators, and time-dependent ROC analysis identified the systemic inflammatory response index (SIRI) as the most effective inflammatory marker. The associations of CKM stages and SIRI with mortality were evaluated.

Results: Over a median follow-up of 109 months, 5,583 all-cause deaths and 1,843 CVD-specific deaths occurred. Both advanced CKM stages and elevated SIRI were associated with higher risks of all-cause and CVD mortality. Individuals with advanced CKM stages (Stages 3-4) and elevated SIRI (> 0.81) had the highest risks of all-cause (HR: 1.84, 95% CI: 1.65-2.05) and CVD mortality (HR: 2.50, 95% CI: 2.00-3.12). These associations were particularly pronounced in adults aged < 60 years (P for interaction < 0.001).

Conclusions: Advanced CKM stages and elevated SIRI are associated with increased risks of all-cause and CVD mortality, particularly in younger adults. These findings highlight the significance of targeted interventions to address systemic inflammation and CKM progression, potentially improving long-term outcomes in high-risk populations.