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Carbohydrate antigen-125 is a mirror of both left and right sides of the heart.

To the Editor: 
 
We read with great interest Ordu and colleagues' recent comparison, for purposes of heart-failure prognostication, of carbohydrate antigen-125 (CA-125) and N-terminal pro-brain natriuretic peptide (NT-proBNP).1 They found that CA-125 level significantly correlated with New York Heart Association functional class, pulmonary artery pressure, microalbuminuria, and creatine kinase-MB fraction, and with levels of hemoglobin, albumin, and NT-proBNP. They also showed that CA-125 levels greater than 32 U/mL and NT-proBNP levels greater than 5,300 μg/mL had independent prognostic value for major adverse events and death. They conclude that baseline CA-125 and NT-proBNP levels are comparably reliable as heart-failure markers and that CA-125 can be used for prognostication in cases of heart failure. 
 
Carbohydrate antigen-125 is produced by ovarian tumors and by normal cells derived from celomic epithelium in response to various stimuli. The first study investigating possible clinical and hemodynamic associations of tumor markers with chronic heart failure was published by Nagele and associates.2 D'Aloia and colleagues3 showed that elevations in CA-125 were related not only to elevations in right atrial pressure, systolic pulmonary artery pressure, and pulmonary artery capillary wedge pressure, but also to left ventricular diastolic dysfunction. 
 
Fluid overload and high venous pressure due to heart failure increase the congestion and pressure in mesothelial cells. Inflammatory markers such as interleukin-6, interleukin-10, and tumor necrosis factora are all elevated in heart failure. Serosal irritation due to inflammation, mechanical stress, or fluid congestion might stimulate mesothelial cells to release CA-125.4,5 
 
In a previous study performed by Yilmaz and coworkers,6 the authors searched for factors associated with elevated CA-125 levels and its impact on some clinical endpoints. One hundred fifty patients who had detailed transthoracic echocardiographic examination within ±1 week of CA-125 sampling were enrolled in the final study. When patients were monitored, CA-125 levels correlated negatively with ejection fraction (EF) and correlated positively with systolic pulmonary artery pressure. In the whole group, patients with right ventricular (RV) dilation had significantly higher CA-125 levels than did those without RV dilation. This study revealed that depressed EF, RV dilation, and pericar-dial effusion were independent predictors of high CA-125 levels. Patients with high CA-125 levels experienced more frequent hospitalization, atrial fibrillation, and death.6 The authors included not only systolic heart-failure patients but all study patients with available results and found that CA-125 levels correlated with left ventricular EF and systolic pulmonary artery pressure; further, high CA-125 level was associated with pericardial effusion and with RV and right atrial dilation. The CA-125 level was associated not only with systolic heart failure but with poor right-sided heart function. 
 
Yilmaz and associates also performed a study of the role of CA-125 in the identification of RV failure in chronic obstructive pulmonary disease (COPD).7 Patients with COPD had significantly higher CA-125 levels than did control subjects. Levels of CA-125 correlated with systolic pulmonary artery pressure, tricuspid annular plane systolic excursion, and tricuspid lateral annulus S velocity. They concluded that CA-125 can be used as a biomarker of RV failure in COPD patients. 
 
In summary, CA-125 is related to many measures of systolic and diastolic function. Also, it is a useful marker of heart-failure prognosis. The CA-125 level is independently influenced by left ventricular EF, RV dilation, and pericardial effusion. We believe that plasma CA-125 is a marker of conditions on both sides of the heart. 
 
 
Taner Sen, MD 
 
Department of Cardiology, Kutahya Evliya Celebi Education & Research Hospital, Kutahya, Turkey 
 
 
 
Tolga Aksu, MD 
 
Department of Cardiology, Kocaeli Derince Education & Research Hospital, Kocaeli, Turkey 
 
 
 
Mehmet Birhan Yilmaz, MD 
 
Department of Cardiology, Cumhuriyet University, Sivas, Turkey