Clinical Role of CA125 in Worsening Heart Failure: A BIOSTAT-CHF Study Subanalysis

Objectives: The aim of this study was to evaluate the association between antigen carbohydrate 125 (CA125) and the risk of 1-year clinical outcomes in patients with worsening heart failure (HF). Background: CA125 is a widely available biomarker that is up-regulated in patients with acute HF and has been postulated as a useful marker of congestion and risk stratification. Methods: In a large multicenter cohort of patients with worsening HF, either in-hospital or in the outpatient setting, the independent associations between CA125 and 1-year death and the composite of death/HF readmission (adjusted for outcome-specific prognostic risk score [BIOSTAT risk score]) were determined by using the Royston-Parmar method (N = 2,356). In a sensitivity analysis, the prognostic implications of CA125 were also adjusted for a composite congestion score (CCS). Data were validated in the BIOSTAT-CHF (Biology Study to Tailored Treatment in Chronic Heart Failure validation) cohort (N = 1,630). Results: Surrogates of congestion, such as N-terminal pro–B-type natriuretic peptide and CCS, emerged as independent predictors of CA125. In multivariable survival analyses, higher CA125 was associated with an increased risk of mortality and the composite of death/HF readmission (p < 0.001 for both comparisons), even after adjustment for the CCS (p < 0.010 for both comparisons). The addition of CA125 to the BIOSTAT score led to a significant risk reclassification for both outcomes (category-free net reclassification improvement = 0.137 [p < 0.001] and 0.104 [p = 0.003] respectively). All outcomes were confirmed in an independent validation cohort. Conclusions: In patients with worsening HF, higher levels of CA125 were positively associated with parameters of congestion. Furthermore, CA125 remained independently associated with a higher risk of clinical outcomes, even beyond a predefined risk model and clinical surrogates of congestion.