Abstract
BACKGROUND: The Cardiovascular-Kidney-Metabolic (CKM) syndrome underscores the complex interactions among metabolic disorders, kidney disease, and cardiovascular conditions. Insulin resistance (IR) and inflammation are crucial in CKM syndrome development, but their combined effect in stages 0-3 remains unclear. METHODS: Using data from the National Health and Nutrition Examination Survey (NHANES), we included 18,295 participants with CKM syndrome stages 0-3 from 10 cycles between 1999 and 2018. IR was assessed using the estimated glucose disposal rate (eGDR), and systemic inflammation was evaluated using the Systemic Inflammation Response Index (SIRI). The primary endpoint was all-cause mortality, and the secondary endpoint was cardiovascular disease (CVD) mortality. RESULTS: Over an average follow-up period of 121 months, we recorded 1,998 all-cause deaths and 539 CVD deaths. Both eGDR and SIRI were independent risk factors for mortality. The hazard ratios (HR) for eGDR were 0.90 (0.86, 0.94) for all-cause mortality and 0.85 (0.78, 0.93) for CVD mortality, per unit increase in eGDR. For SIRI, the HRs were 1.16 (1.11, 1.21) for all-cause mortality and 1.33 (1.19, 1.46) for CVD mortality, per unit increase in SIRI. Compared to individuals with high eGDR and low SIRI levels, those with low eGDR and high SIRI levels exhibited significantly higher mortality risks, with HRs of 1.97 (1.58, 2.44) for all-cause mortality and 2.35 (1.48, 3.73) for CVD mortality. Subgroup analysis revealed that the combined impact of eGDR and SIRI was particularly significant in patients under 60 years old. CONCLUSION: In CKM syndrome stages 0-3, eGDR and SIRI have joint effect on mortality. Combining these markers can help identify high-risk individuals early, enabling timely monitoring and intervention to improve outcomes.