Clinical Role of Carbohydrate Antigen 125 in Worsening Heart Failure:a BIOSTAT-CHF study sub-analysis

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 BIOSTAT risk score) were determined with the Royston-Parmar method (n=2356). In a sensitivity analysis, the prognostic implications of CA125 were also adjusted for a clinical congestion score (CCS). Data were validated in the BIOSTAT-CHF validation cohort (n=1630).Results. Surrogates of congestion, such as NT-proBNP and a 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. n 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