76a2b2158c7a4877a4d637f404b6a8d9 biomolecules-15-01260.pdf c76b6ed5ebd9d256179778d539f19b1bdacb6b8a biomolecules-15-01260.pdf 970f23019ed6d0c5cb19b0099e81c92553005d7a7aa78f3bd6a880c7547c92bd biomolecules-15-01260.pdf Title: Modulating Effect of Carbohydrate Antigen 125 on the Prognostic Value of High-Sensitivity C-Reactive Protein in Heart Failure Subject: Inflammation and congestion are key pathophysiological processes in heart failure (HF). Our aim was to evaluate the potential modulatory effect of carbohydrate antigen 125 (CA125) on inflammation, assessed by high-sensitivity C-reactive protein (hs-CRP). We analyzed a cohort of 4043 consecutive patients in whom hs-CRP and CA125 levels were measured during a hospitalization for acute HF. Multivariate Cox regression models were applied to assess the association between the biomarkers and all-cause mortality and death/HF rehospitalization at 6 months. In multivariable analysis, a significant interaction between hs-CRP and CA125 was observed for both outcomes (p-value for interaction = 0.036 and <0.001, respectively). hs-CRP was significantly associated with an increased risk of death (HR = 1.27; 95% CI 1.16–1.41; p < 0.001) and death/HF rehospitalization (HR = 1.18; 95% CI 1.09–1.28; p < 0.001) if CA125 > 35 U/mL. In contrast, hs-CRP was not predictive of events when CA125 35 U/mL. In conclusion, in patients with acute HF, the association between hs-CRP and clinical outcomes was modulated by CA125 levels. hs-CRP was associated with a higher risk of events only in patients with elevated CA125. These findings support a potential modulatory and amplifying role for CA125 in the inflammatory response in HF. Keywords: acute heart failure; CA125; hs-CRP; inflammatory modulator Author: Enrique Santas, Arancha Martí-Martínez, Elena Revuelta-López, Sandra Villar, Rafael de la Espriella, Patricia Palau, Pau Llàcer, Gema Miñana, Enrique Rodriguez-Borja, Arturo Carratalá, Arantxa Gonzalez, Antoni Bayés-Genís, Juan Sanchis and Julio Núñez Creator: LaTeX with hyperref Producer: pdfTeX-1.40.25; modified using OpenPDF 1.4.2 CreationDate: Sat Aug 30 10:58:47 2025 CEST ModDate: Sat Aug 30 11:02:43 2025 CEST Custom Metadata: yes Metadata Stream: no Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 15 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 941481 bytes Optimized: no PDF version: 1.5 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- TNBSFT+CMSY10 Type 1 Builtin yes yes yes 126 0 AIRHKL+VnURWPalladioL Type 1 Custom yes yes yes 127 0 WNWTFR+VnURWPalladioL-Bold Type 1 Custom yes yes yes 128 0 KHVNJB+URWPalladioL-Ital Type 1 Custom yes yes yes 129 0 NCFYMM+URWPalladioL-Bold Type 1 Custom yes yes yes 130 0 YWQQEX+URWPalladioL-Roma Type 1 Custom yes yes yes 131 0 XSVVIN+EURM10 Type 1 Builtin yes yes yes 180 0 QLBIEB+URWPalladioL-BoldItal Type 1 Custom yes yes yes 210 0 OOKBAN+PalatinoLinotype TrueType WinAnsi yes yes no 232 0 OOKBAN+PalatinoLinotype TrueType WinAnsi yes yes no 249 0 OOKBAN+PalatinoLinotype TrueType WinAnsi yes yes no 255 0 OOKBAL+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 256 0 Jhove (Rel. 1.28.0, 2023-05-18) Date: 2026-06-05 04:53:03 CEST RepresentationInformation: biomolecules-15-01260.pdf ReportingModule: PDF-hul, Rel. 1.12.4 (2023-03-16) LastModified: 2026-06-04 15:34:51 CEST Size: 941481 Format: PDF Version: 1.5 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 431 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: ViewerPreferences: HideToolbar: false HideMenubar: false HideWindowUI: false FitWindow: true CenterWindow: false DisplayDocTitle: false NonFullScreenPageMode: UseNone Direction: L2R ViewArea: CropBox ViewClip: CropBox PrintArea: CropBox PageClip: CropBox PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Item: Title: Materials and Methods Children: Item: Title: Study Group and Protocol Item: Title: Biomarkers Measurement Item: Title: Follow-Up and Endpoints Item: Title: Statistical Analysis Item: Title: Results Children: Item: Title: Baseline Characteristics Across hs-CRP/CA125 Categories Item: Title: hs-CRP and 6-Month Adverse Outcomes Item: Title: hs-CRP and Clinical Outcomes Across CA125 Item: Title: Discussion Children: Item: Title: Inflammation and Congestion: Two Converging Pathophysiological Axes in HF Item: Title: CA125 as a Biomarker Beyond Congestion, a Modulator of Inflammatory Pathways? Item: Title: Potential Clinical Implications Item: Title: Limitations Item: Title: Conclusions Item: Title: Appendix A Item: Title: References Info: Title: Modulating Effect of Carbohydrate Antigen 125 on the Prognostic Value of High-Sensitivity C-Reactive Protein in Heart Failure Author: Enrique Santas, Arancha Martí-Martínez, Elena Revuelta-López, Sandra Villar, Rafael de la Espriella, Patricia Palau, Pau Llàcer, Gema Miñana, Enrique Rodriguez-Borja, Arturo Carratalá, Arantxa Gonzalez, Antoni Bayés-Genís, Juan Sanchis and Julio Núñez Subject: Inflammation and congestion are key pathophysiological processes in heart failure (HF). Our aim was to evaluate the potential modulatory effect of carbohydrate antigen 125 (CA125) on inflammation, assessed by high-sensitivity C-reactive protein (hs-CRP). We analyzed a cohort of 4043 consecutive patients in whom hs-CRP and CA125 levels were measured during a hospitalization for acute HF. Multivariate Cox regression models were applied to assess the association between the biomarkers and all-cause mortality and death/HF rehospitalization at 6 months. In multivariable analysis, a significant interaction between hs-CRP and CA125 was observed for both outcomes (p-value for interaction = 0.036 and <0.001, respectively). hs-CRP was significantly associated with an increased risk of death (HR = 1.27; 95% CI 1.16–1.41; p < 0.001) and death/HF rehospitalization (HR = 1.18; 95% CI 1.09–1.28; p < 0.001) if CA125 > 35 U/mL. In contrast, hs-CRP was not predictive of events when CA125 35 U/mL. In conclusion, in patients with acute HF, the association between hs-CRP and clinical outcomes was modulated by CA125 levels. hs-CRP was associated with a higher risk of events only in patients with elevated CA125. These findings support a potential modulatory and amplifying role for CA125 in the inflammatory response in HF. 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