Determinants of CA125 elevation and the comparative prognostic value of the NTproBNP/CA125 ratio in heart failure
D Gruson, A Khatib, A C PouleurAbstract
Objective
Carbohydrate Antigen 125 (CA125) is a key biomarker reflecting congestion and inflammation in heart failure (HF). This study aimed to first, identify the independent determinants of CA125 elevation in heart failure with reduced ejection fraction (HFrEF) and second, compare the prognostic performance of the NTproBNP/CA125 ratio against its powerful individual components (NT-proBNP and CA125) for all-cause mortality.
Methods
We analyzed data from 108 consecutive HFrEF patients. Independent determinants of log-transformed CA125 were identified using multiple linear regression, including age, sex, ejection fraction (EF), estimated glomerular filtration rate (eGFR), NT-proBNP, and soluble Suppression of Tumorigenicity 2 (sST2). The prognostic value of the NTproBNP/CA125 ratio and individual markers was assessed using Cox regression.
Results
CA125 concentrations were strongly associated with clinical severity, as reflected by New York Heart Association (NYHA) functional class (p < 0.001). In multivariate linear regression analysis, CA125 elevation was independently predicted by higher sST2 levels (p < 0.001), indicating the contribution of myocardial stress, inflammation, and fibrotic activity, as well as by higher NT-proBNP concentrations (p = 0.013), reflecting neurohormonal activation and increased myocardial wall stress. In addition, lower left ventricular ejection fraction was independently associated with increased CA125 levels (p = 0.044), highlighting the link between CA125 elevation and advanced ventricular dysfunction. Regarding prognosis, both CA125 (hazard ratio [HR] = 1.0010, p < 0.001) and NT-proBNP (HR = 1.000066, p < 0.001) emerged as strong univariate predictors of all-cause mortality. In contrast, the NT-proBNP/CA125 ratio did not demonstrate significant prognostic value (HR = 1.0004, p = 0.420), suggesting that the combination of these biomarkers into a simple ratio does not provide incremental prognostic information beyond that offered by each marker individually.
Conclusion
CA125 acts as an integrated biomarker, with its elevation independently driven by the convergence of inflammation/fibrosis (sST2) and neurohormonal activation (NT-proBNP), alongside ventricular dysfunction (EF). While the simple NTproBNP/CA125 ratio does not offer superior prognostic information over its individual components, the strong and distinct predictive power of CA125 and NT-proBNP underscores the necessity of a multi-marker approach to capture the diverse pathophysiological pathways contributing to risk stratification in HFrEF. The ratio's lack of added value suggests that the prognostic information of these two markers is best utilized separately.