• Julio Núñez, Antoni Bayés-Genís, Elena Revuelta-López, Jozine M Ter Maaten, Gema Miñana, Jaume Barallat, Adriana Cserkóová, Vicent Bodi, Agustín Fernández-Cisnal, Eduardo Núñez, Juan Sanchis, Chim Lang, Leong L Ng, Marco Metra, and Adriaan A Voors.
• Cardiology Department, Hospital Clínico Universitario de Valencia, Universitat de Valencia, INCLIVA, Valencia, Spain; CIBER Cardiovascular, Madrid-Spain.
• JACC Heart Fail. 2020 May 1; 8 (5): 386-397.

ObjectivesThe 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).BackgroundCA125 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.MethodsIn 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).ResultsSurrogates 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.ConclusionsIn 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.Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

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