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

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.

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.

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).

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.

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.