CALLY Index as a Comprehensive Biomarker for Heart Failure Risk: Findings from NHANES 1999–2010

Background Heart failure (HF) is a critical global health issue characterized by high morbidity, mortality, and economic burden. The interplay of chronic inflammation, malnutrition, and immune dysregulation is central to HF pathogenesis. The C-reactive protein-Albumin-Lymphocyte (CALLY) index, a composite biomarker that integrates inflammatory, nutritional, and immune parameters, offers a novel, holistic approach to HF risk prediction. However, its association with HF prevalence and potential clinical utility remains underexplored. Methods This study utilized data from the NHANES 1999–2010 cohort, encompassing 14,900 participants after stringent inclusion criteria. The CALLY index was computed as albumin (g/L) × lymphocyte count (10⁹/L) / C-reactive protein (CRP, mg/L). Logistic regression models were utilized to assess the relationship between CALLY index quartiles and HF prevalence, with adjustments made for demographic, socioeconomic, and clinical factors. Nonlinear associations were examined using restricted cubic spline analysis, while subgroup analyses evaluated differences across age, gender, and ethnicity. Results Participants with HF (n = 659, 4.4%) exhibited significantly lower CALLY index values compared to those without HF. Multivariate analyses revealed a robust, dose-dependent association between higher CALLY index quartiles and HF risk (Q4 vs. Q1: adjusted OR = 7.49, 95% CI: 5.89–9.52, P < 0.001). Restricted cubic spline analysis identified a threshold value of 692, above which HF risk sharply increased. Subgroup analyses highlighted significant heterogeneity, with stronger associations observed among older adults (≥ 60 years), males, and non-Hispanic Black populations, suggesting demographic-specific predictive utility. Conclusions The CALLY index serves as a low-cost, readily accessible biomarker for HF risk stratification, integrating critical dimensions of inflammation, nutrition, and immune function. Its nonlinear association with HF risk and identified threshold offer practical insights for early detection and intervention. Tailored strategies for high-risk demographic groups, such as older adults and non-Hispanic Black individuals, could enhance its clinical application. Further longitudinal studies and interventional trials are required to confirm these findings and evaluate the broader applicability of the CALLY index in cardiovascular risk management.