Julio Núñez1, Antoni Bayés-Genís2, Elena Revuelta-López3, Jozine M Ter Maaten4, Gema Miñana1, Jaume Barallat5, Adriana Cserkóová6, Vicent Bodi1, Agustín Fernández-Cisnal7, Eduardo Núñez7, Juan Sanchis1, Chim Lang8, Leong L Ng9, Marco Metra10, Adriaan A Voors11. 1. Cardiology Department, Hospital Clínico Universitario de Valencia, Universitat de Valencia, INCLIVA, Valencia, Spain; CIBER Cardiovascular, Madrid-Spain. 2. CIBER Cardiovascular, Madrid-Spain; Cardiology Department and Heart Failure Unit, Hospital Universitari Germans Trias i Pujol, Badalona, Department of Medicine, Autonomous University of Barcelona, Barcelona, Spain. 3. CIBER Cardiovascular, Madrid-Spain; ICREC Research Program, Germans Trias i Pujol Health Science Research Institute, Can Ruti Campus, Badalona, Spain. 4. Cardiology Department, University of Groningen, University Medical Centre Groningen, Groningen, the Netherlands. 5. Biochemistry Department, Hospital Universitari Germans Trias I Pujol, Badalona, Spain. 6. ICREC Research Program, Germans Trias i Pujol Health Science Research Institute, Can Ruti Campus, Badalona, Spain. 7. Cardiology Department, Hospital Clínico Universitario de Valencia, Universitat de Valencia, INCLIVA, Valencia, Spain. 8. Division of Molecular and Clinical Medicine, School of Medicine, University of Dundee, Dundee, United Kingdom. 9. Department of Cardiovascular Sciences University of Leicester, Clinical Sciences Wing Glenfield General Hospital Leicester, Leicester, United Kingdom. 10. Cardiology Department of Medical and Surgical Specialties, Radiologic Sciences, and Public Health, University of Brescia, Brescia, Italy. 11. Cardiology Department, University of Groningen, University Medical Centre Groningen, Groningen, the Netherlands. Electronic address: a.a.voors@umcg.nl.
Abstract
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.
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.
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