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RESEARCH PRODUCT

Antigen carbohydrate 125 in heart failure: Not just a surrogate for serosal effusions?

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Wehave readwith interest the letter CA-125andheart failure:Deja vu or “still to be seen” by Topatan B and Basaran A [1] where the authors concisely reviewed the current pathophysiological knowledgeof CA125 in heart failure (HF). As discussed by these authors, the pathogenesis of this biomarker's elevation inHF is complex andmultifactorial,with apparently different driven forces. For instances, a proinflammatory stimulus (IL-1, tumour necrosis factor-α, lipopolysaccharide) and mesothelial-induced stress appear thekeymechanisms related to the increaseof this biomarker in HF [1–5]. However, no clear evidence exists in regard to how these two mechanisms differentially participate in CA-125 elevation in individual patients with HF. Therefore, despite the fact that the presence of serosal effusion has shown to be importantly correlated to higher CA125 values [1], considering this biomarker just a simple surrogate for serosal effusion seems quite unfair. Along this line, we have new evidence pointing-out against the fact that CA125elevation represents justmerely a surrogate for mesothelial irritation. Since July 2008 to the end of July 2010we included in an ambulatory continuous peritoneal dialysis program17 patientswith advanced congestive HF that meet the following criteria: a) NYHA III/IV despite standard pharmacological treatment; b) estimated glomerular filtration rate b60 ml/min/1.73 m; c) clinical evidence of systemic congestion and; d) at least two admissions for acute HF. Clinical characteristics of the sample are shown in the supplementary file. The peritoneal dialysis program consisted of 2 to 3-day time exchange with dialysate solution (1.36%–2.27% of glucose) with the aim to decrease the grade of systemic congestion. In these patients, and despite the peritoneal irritation induced by the presence of an osmotic solution into the peritoneum, we observed a sustained and sizable CA125 reduction at 45 [70.86 (46.14–206.7)U/ml vs 28.77 (22.09–38.6)U/ml, p=0.002] and 120 days after dialysis onset [70.86 UI/ml (46.14–206.7) vs 27.47 (16.7– 30.05)UI/ml, pb0.001] as shown in Fig. 1a. In fact, whereas only 11.8% (n=2) of patients showed CA125 serum values within normal ranges (CA125b35 U/ml) at the moment of peritoneal dialysis onset, 70.6% (n=12) and 82.3% (n=14) of the patients displayed CA125b35 U/ml at 45 and 120 days, respectively (pb0.05 for both comparisons). Paralleling to this decrease in CA125 values, an improvement in the NYHA functional class and an increase of the relative lymphocyte count (as a marker of improvement of the inflammatory state) were observed (Fig. 1b and c). With this data, we aim to stress the concept that CA125 is more than a simple surrogate for the presence of serosal effusions and mesothelial irritation, under the assumption that peritoneal dialysate is a well known irritator of the peritoneum [6,7]. Nevertheless, why most of the studies assessing the role of CA125 in HF have shown a close relationship with the presence of serosal effusions? Obviously, this question is still unsolved, although we hypothesize that CA125 is synthesized by mesothelial cells in response to certain mechanisms activated in the congestive states, and supported by recent evidence showing a pathogenic role of venous congestion in triggering a proinflammatory state [8,9], which at the end, would activate themesothelial cells to synthesize CA125. In this framework, CA125 increase and serosal effusion are parallel processes caused by the similar pathophysiological mechanisms although not necessarily a cause–effect phenomenon. No matter which pathophysiological mechanism is behind the kinetic of this biomarker, there are certain properties that make CA125 serum determination a promising tool for HF risk stratification: a) wide availability, b) additional prognostic utility beyond clinical and biochemical markers (including natriuretic peptides) [5] and; c) in contrast of cytokines and other inflammatory markers that exhibit high variability [10], CA125 changes over time are sustained (half-life higher than 1 week) and correlated with clinical status and prognosis [11,12]. Finally, we believe there is still much to be seen regarding this biomarker, and encourage researchers in HF field to focus into the pathophysiology, biological role and the clinical utility of this glycoprotein for monitoring and guiding therapy in HF setting. The following is the supplementary material related to this article. Table 1. Baseline characteristics of the study sample. Supplementary materials related to this article can be found online at doi:10.1016/j.ijcard.2010.12.027. This study was supported by unrestricted grants from the Ministerio de Sanidad y Consumo, Instituto de Salud Carlos III, RED HERACLES RD06/0009/1001 (Madrid, Spain), Ayuda para proyectos de grupos emergentes ano 2010 de la Conselleria de Sanitat de Valencia (DOCV 6.175, 30/12/2009-Annex III), Sociedad Espanola de Cardiologia (Beca Esteve 2009) and Fresenius Medical Care. The authors of this manuscript have certified that they comply with the Principles of Ethical Publishing in the International Journal of Cardiology [13].