Unlocking the Prognostic Power of the m-CALLY Index in Cardiovascular-Kidney-Metabolic Syndrome

Introduction: Cardiovascular-Kidney-Metabolic (CKM) syndrome is a multi- -system disorder driven by chronic inflammation and immune-nutritional imbalances. This study aimed to evaluate the prognostic value of the modified C-reactive protein-- to-albumin-to-lymphocyte (m-CALLY) index within the integrative CKM framework. Methods: Data from 9,135 adults with CKM syndrome (weighted population: 76,768,947) were extracted from NHANES (2001-2010). Participants were stratified into Stages 0-4 based on the 2023 AHA scientific statement. The m-CALLY index was calculated and log-transformed, with mortality assessed via National Death Index linkage. Predictive performance was compared against the Prognostic Nutritional Index (PNI) using log-likelihood ratio tests. Results: During follow-up, 1,881 all-cause and 494 cardiovascular deaths were identified. Multivariable Cox analysis demonstrated that the m-CALLY index was inversely associated with mortality risk. After full adjustment, each 1-SD increase in m-CALLY was associated with a 13% lower risk of all-cause mortality (HR: 0.87, 95% CI: 0.83-0.90). Compared to the lowest quartile (Q1), the highest quartile (Q4) exhibited a 39% reduction in all-cause mortality (HR: 0.61, 95% CI: 0.49-0.75) and a 17% reduction in cardiovascular mortality (HR: 0.83, 95% CI: 0.76-0.90). Notably, m-CALLY demonstrated superior predictive accuracy over the PNI index (log-likelihood: −4288.45 vs. −4333.92). These associations remained consistent across all CKM stages (P-interaction > 0.05). discussion: This study investigated the association between the modified C-reactive protein-to-albumin-to-lymphocyte (m-CALLY) index and all-cause and cardiovascular mortality in individuals with CKM syndrome, using data from the National Health and Nutrition Examination Survey (NHANES). The researchers hypothesized that lower m-CALLY levels, reflecting elevated inflammation and compromised immunonutritional status, would independently predict higher mortality risks, especially in advanced CKM stages. The findings of this study have the potential to establish the m-CALLY index as a practical and cost-efficient tool for identifying high-risk CKM patients who might benefit from targeted anti-inflammatory or nutritional interventions Discussion: The study’s findings suggest that integrating inflammation, nutrition, and immunity via the m-CALLY index offers a more comprehensive assessment of the CKM pathophysiological burden than traditional indices. As a routine laboratory-based tool, it provides a cost-effective strategy for risk stratification across the entire CKM spectrum Conclusion: Elevated m-CALLY levels are independently associated with significantly reduced risks of all-cause and cardiovascular mortality in the CKM population. This index may facilitate integrated risk stratification and personalized management in clinical practice.