In ACS patients, a number of novel biomarkers have been proposed in prognosis evaluation and risk stratification. CA125 is a well-known tumor marker for diagnosis, monitoring, and risk stratification in ovarian malignancy; it has become an increasingly promising biomarker in HF in the recent two decades [10, 20, 21].
In this study, the CA125 levels increased with the severity of HF in patients with Killip Ⅰ-Ⅲ, but the CA125 levels did not increased significantly in patients with Killip Ⅳ. This is probably because the Killip Ⅳ patients developed AHF several days after admission; however, the CA125 levels were measured only at admission. Hemodynamic changes after ACS resulted in an increase in congestion and hydrostatic pressure in the mesothelium, thereby provoking mesothelial cells to initiate CA125 synthesis [22]. The kinetics of CA125 release from mesothelial cells in ACS patients is not known; it may be similar to NT-proBNP. The values obtained after a few days after onset of symptoms may have superior prognostic value when compared with the measurements on admission [23].
In this study, 19.8% of total patients suffered from AHF, which was consistent with the incidence of post-myocardial infarction HF [24]. Patients with acute myocardial infarction are more likely to have higher CA125 levels compared with those with UA, whether STEMI or NSTEMI. The is probably because patients with myocardial infarction lose more functional cardiomyocytes due to myocardial stunning and necrosis compared to UA patients, increasing the risk of AHF. A retrospective cohort study of ACS patients also revealed that the incidence of HF among STEMI and NSTEMI was higher than UA patients during hospitalization and one-year follow-up [25].
So far, the relationship between echocardiographic parameters and CA125 is not conclusive due to the controversial results obtained from different studies. This study focused on the relationship between CA125 and LVEDD, and LVEF in female ACS patients. CA125 showed a weak positive correlation with LVEDD and negative correlation with LVEF. CA125 also demonstrated weak negative correlation with LVEF in CHF patients in another retrospective study [9]. However, in another study of ACS patients, CA125 was found to be related to LVEDD (r = 0.66, P < 0.001) and LVEF (r = –0.37, P < 0.01) [15]. CA125 levels were correlated with the deceleration time of early filling on transmitral Doppler (r = –0.63, p < 0.05), pulmonary artery pressure (r = 0.66, p < 0.05) and right atrial pressure (r = 0.69, p < 0.05). However, no significant correlation was observed between CA125 concentration and LVEF or LVEDD. In another study including 77 CHF patients, a weak correlation was observed between the CA125 levels and right ventricular systolic pressure, but no significant correlation was observed between CA125 and LVEDD, LVEF, or DT [9]. Hakki Yilmaz et al. analyzed the relationship between CA125 levels and left ventricular function in patients with end-stage renal disease on maintenance hemodialysis [26]. CA125 levels showed a significant positive correlation with LVEDD (r = 0.599, p < 0.001), left ventricular end-systolic diameter (LVESD, r = 0.750, p < 0.001), and left ventricular mass index (LVMI, r = 0.378, p < 0.05) and negative correlation with LVEF (r = –0.878, p < 0.001).
In contrast to previous studies, CA125, as shown in this study, is not related to BNP, but it is an excellent predictor of AHF in ACS patients during hospitalization, even better than BNP. Robust data showed that elevated BNP is highly predictive of AHF and all-cause mortality in ACS patients when compared with lower levels. Our results are also different from those of Azra Durak-Nalbantic1 et al., who found a significant although weak positive correlation of CA125 and BNP in CHF patients (r = 0.293, p < 0.05) [27]. Dursum Duman et al. studied the relationship between the CA125 and BNP concentrations in patients with advanced HF: LnCA125 was significantly correlated with LnBNP (r = 0.78, p < 0.001), and CA125 levels were independently associated with BNP (β = 0.58, p < 0.001) [11]. Luisa De Gennaro also revealed that elevated CA125 levels identified ACS patients with AHF with a higher specificity (97.1 vs. 31.4%), positive predictive value (83.3 vs. 33.3%), and accuracy (83.0 vs. 48.9%) when compared with BNP [15].
Many studies have already demonstrated that CA125 is a robust prognostic marker in both acute or chronic HF, and elevated CA125 level is associated with poor short-term and long-term outcomes, including mortality and rehospitalization rates. Julio Núñez et al. showed a positive trend between the quartile 1 to 4 of CA125 and 6 months’ mortality in patients with AHF [28]; similar results also obtained in the latest research in patients with decompensated HF [21]. In a retrospective study of 55 CHF patients who underwent cardiac transplantation, the survival was significantly inferior in the group with elevated CA125 level compared with normal group at two-, five-, and eight-years follow-up [29]. A recent systematic meta-analysis including 16 studies showed that elevated CA125 levels were associated with a 68% increase in all-cause mortality (eight studies, HRs: 1.68, 95% CI: 1.36 to 2.07; p < 0.001; I2: 74%) and 77% increase in HF-related readmissions (five studies, HRs: 1.77, 95% CI: 1.22 to 2.59; p < 0.01; I2: 73%) in AHF patients [30]. In this study, we also confirm that elevated CA125 levels are associated with higher mortality in female ACS patients both during hospitalization and mid-term follow-up. Similar results were obtained by Felipe Falcão et al.; patients with high CA125 values according to the optimal cutoff (11.48U/mL) had a higher rate of mortality at six months than those with low CA125 values in STEMI cohort [31].
Some limitations of this study should be highlighted. First, this is a relatively small-sized retrospective study of only female ACS patients conducted in a single center, which may limit the extrapolation of our results to all populations. The results of this study should be validated in larger trials and male crowd. Second, CA125 concentrations were determined only at hospital admission. The level might depend on the time elapsed from the onset of chest pain; serial measurement may provide more accurate prognostic value. Third, we cannot ignore the fact that factors that influence mortality were not been considered in our analysis (e.g., treatment during hospitalization and follow-up).