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.
The BIOSTAT-CHF was funded by the European Commission (FP7-242209-BIOSTAT-CHF; EudraCT 2010-020808-29) and CIBER Cardiovascular (16/11/00420 and 16/11/00403). Dr. Metra has received consulting honoraria as a committee member for clinical trials from Amgen, Fresenius, and Vifor Pharma; has received consulting honoraria as advisory board member from Bayer; and has received honoraria for speeches from Abbott and Edwards. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
The authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the JACC: Heart Failureauthor instructions page.
