C-reactive protein-albumin-lymphocyte (CALLY) index and all-cause and cardiovascular mortality in the general population: a national health and nutrition examination survey analysis.

backgroundThe C-reactive protein-albumin-lymphocyte (CALLY) index is a composite biomarker integrating systemic inflammation (elevated C-reactive protein), nutritional status (decreased albumin), and immune function (reduced lymphocyte count). Its prognostic significance for mortality in the general population remains insufficiently characterized.

methodsWe analyzed data from the National Health and Nutrition Examination Survey (NHANES, 1999-2010), comprising 11,797 adults (5,671 men [weighted 48.4%] and 6,126 women [weighted 51.6%]; median age, 45 years). The CALLY index was calculated for each participant. Associations between the CALLY index and all-cause and cardiovascular mortality were evaluated using Kaplan-Meier analysis (for descriptive visualization), weighted multivariable Cox proportional hazards regression, Fine-Gray competing risk models, and restricted cubic spline (RCS) regression. Predictive performance was assessed using time-dependent receiver operating characteristic (ROC) analysis. The incremental predictive value beyond established risk factors was quantified using the integrated discrimination improvement (IDI) and category-free net reclassification improvement (NRI).

resultsCompared with the lowest quartile, the highest CALLY quartile was associated with lower risks of all-cause mortality (multivariable-adjusted hazard ratio [HR], 0.61; 95% confidence interval [CI], 0.51-0.74; P < 0.001) and cardiovascular mortality (HR, 0.51; 95% CI, 0.39-0.68; P < 0.001). In Fine-Gray competing risk models, the subdistribution hazard ratio for cardiovascular mortality was 0.55 (95% CI, 0.39-0.76; P < 0.001), with a lower cumulative incidence of cardiovascular death in quartile 4 versus quartile 1 (Gray's test, P < 0.001). RCS analyses revealed significant non-linear associations: an approximately L-shaped relationship for all-cause mortality and a monotonically decreasing non-linear pattern for cardiovascular mortality (both P for non-linearity < 0.001). The CALLY index provided modest incremental predictive value beyond established risk factors for all-cause mortality (IDI, 0.4%; P = 0.007), but individual-level risk reclassification was limited (continuous NRI, 2.7%; P = 0.272). Significant effect modification for all-cause mortality was observed only for alcohol use (P for interaction = 0.005).

conclusionHigher CALLY index values were significantly associated with lower mortality risk. The CALLY index demonstrated a significant, independent, and non-linear inverse association with all-cause and cardiovascular mortality in US adults. Its standalone predictive discrimination was modest (time-dependent AUC < 0.70), but its integration into multivariable risk models provided modest yet statistically significant incremental prognostic information (IDI, 0.4%; P = 0.007). Individual-level risk reclassification was limited (continuous NRI, 2.7%; P = 0.272). These findings suggest that CALLY may serve as a complementary biomarker for risk stratification when integrated with conventional risk factors rather than as a standalone prediction tool.