Age-related associations between the CALLY index and advanced cardiovascular-kidney-metabolic (CKM) syndrome: Insights from NHANES population data

Cardiovascular disease, chronic kidney disease, and metabolic syndrome often co-occur, forming a complex disorder known as cardiovascular-kidney-metabolic (CKM) syndrome. Identifying biomarkers that reflect inflammation, nutrition, and immune function is crucial for effective risk assessment. The C-reactive protein-albumin-lymphocyte (CALLY) index, which integrates these factors, has not been explored in the context of CKM syndrome. Data from 9 National Health and Nutrition Examination Survey cycles (2001-2018) were used, including 11,866 adults aged 20 years and older. The CALLY index was calculated as (albumin × lymphocyte count) ÷ C-reactive protein and then log-transformed. CKM syndrome was categorized into stages 0 to 4. Multivariable logistic regression and smoothing splines were used to assess associations between the CALLY index and advanced CKM (stages 3 and 4), with subgroup analyses by age and other variables. A higher log-transformed CALLY index was associated with a lower likelihood of advanced CKM (odds ratio per unit increase: 0.90; 95% confidence interval: 0.86-0.95). Individuals in the top tertile had a 21% lower odds of advanced CKM than those in the bottom tertile (odds ratio: 0.79; 95% confidence interval: 0.67-0.93). A threshold effect was observed in individuals under 60 years, with protective effects increasing below a CALLY value of 455 units. The CALLY index is inversely associated with advanced CKM syndrome, reflecting systemic inflammation, nutrition, and immune status. Its age-dependent associations suggest opportunities for early detection and targeted interventions, especially in younger adults. Validation in prospective studies is needed.