Plasma CA125 Levels as a Predictor of Major Adverse Cardiac Events in Patients With Acute Coronary Syndrome: A Six-month Follow-up Study

Abstract

Objectives

Carbohydrate antigen 125 (CA125) is associated with different cardiovascular conditions. This study aimed to determine CA125 levels in patients with acute coronary syndrome (ACS) and the potential relationship between major adverse cardiac events (MACE) in the short-term following.

Methods

This prospective cohort study was conducted in a coronary care unit between May and November 2022. Plasma CA125 levels were measured only once upon hospital admission. Patients were followed for six months. All-cause mortality, recurrent acute coronary syndrome, requirement for revascularization, decompensated heart failure, cardiogenic pulmonary edema, atrial fibrillation, and stroke were recorded as MACE.

Results

A total of 127 patients were included in this study. The mean left ventricular ejection fraction (LVEF) was 50.5 %. The median plasma CA125 level was 14.6 KU/L. There was a, significant positive relationship between CA125 and high-sensitivity cardiac troponin (hs-cTn) (r = 0.315, p < 0.001) and pro–B-type natriuretic peptide (proBNP) (r = 0.423, p < 0.001), and a weak negative relationship with LVEF (r = −0.186, p = 0.037) value.

Conclusions

Plasma CA125 levels were correlated with the pro-BNP and hs-cTn, established ACS biomarkers. An additional notable finding was the weak correlation with LVEF. Elevated plasma CA125 levels might be used to identify patients with ACS who are at higher risk of MACE at six months.

1. Introduction

Recently, biomarkers have become important in predicting cardiovascular (CV) risks [1–3]. Risk stratification of patients with cardiovascular disease (CVD), especially acute coronary syndrome (ACS), in terms of short- and long-term adverse events and the identification of high risk patients, is essential for optimal management. Because atherosclerosis is a multifactorial process, using several markers simultaneously can improve the performance of risk assessment strategies. Obstructive and inflammatory markers such as natriuretic peptides and high-sensitivity C reactive protein are prognostic markers. However, currently available biomarkers are imperfect, and their correct interpretation requires careful evaluation of the specific clinical scenario [4,5].

Carbohydrate antigen 125 (CA125), a glycoprotein belonging to the mucin family, has been accepted as a diagnostic and prognostic marker in CVD such as pericarditis, atrial fibrillation, heart failure and coronary artery disease (CAD), and other heart diseases [5–7]. Since mechanical stress and inflammation can induce CA125 synthesis from mesothelial cells of the peritoneum, pleura, and pericardium, it serves as a prognostic marker for mortality and rehospitalization in patients with heart failure [4]. In addition, a recent meta-analysis showed that high CA125 levels were also associated with hospital readmissions and all-cause mortality in patients presenting with acute heart failure, although none of the included studies evaluated patients with ACS [4,8].

Exacerbation of the inflammatory process leads to coronary atherosclerotic plaque instability and can result in arterial thrombotic occlusion in ACS [9,10]. Mechanical stress and inflammatory stimuli are transmitted to the cytoplasm, leading to morphological and membrane stability change that activates CA125 release from mesothelial cells [6,8]. Thus, congestion and inflammation occur simultaneously. Therefore, CA125 may be a marker for both [6]. The primary aim of this study was to investigate the potential relationship between CA125 levels and ACS. The secondary aim of this study was to evaluate its prognostic role in predicting short-term outcomes in patients with ACS.

2. Materials and methods

The study was conducted at the coronary care unit of a tertiary teaching and research hospital in Istanbul (Turkey).

Ethical approval for the study was obtained from the local ethics committee of the University of Health Sciences, Istanbul Teaching and Research Hospital, Clinical Studies Ethical Committee (Approval number: 146/Date: 06.05.2022). All participants provided written informed consent. The study protocol was conducted in accordance with the Declaration of Helsinki.

2.1. Study population

This observational cohort study was conducted and reported in accordance with the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement.

Patients aged 18–85 years who presented to the emergency department with a suspected ACS, with or without a previous history of ACS, were evaluated between 15 May 2022 and 30 November 2022. ACS was defined as unstable angina (UA) or myocardial infarction (MI) according to the fourth universal definition [11].

A total of 253 patients meeting the inclusion criteria were initially assessed. Among these, 53 patients were excluded because ACS was not angiographically confirmed (defined as the absence of ≥50 % stenosis in at least one coronary artery) and/or because a diagnosis of type 1 myocardial infarction was not established. An additional 73 patients were excluded due to missing pre–percutaneous coronary intervention (PCI) measurements of CA125, high-sensitivity cardiac troponin (hs-cTn), pro–B-type natriuretic peptide (proBNP), or left ventricular ejection fraction (LVEF). Ultimately, a total of 127 patients were included in the study and followed for six months. Figure 1 shows the patient flow diagram of the study.

Fig. 1.

Patient flow diagram.

2.2. Exclusion criteria

Patients aged <18 years, pregnant or breastfeeding, patients who did not undergo PCI, those who failed to provide written informed consent, and patients with cognitive impairment were excluded from the study.

2.3. Data collection

CA125, hs-cTn, proBNP, and LVEF levels were obtained once at hospital admission, prior to PCI, with LVEF derived from transthoracic echocardiography performed at the same time. Demographic characteristics, cardiovascular risk factors, and blood pressure measurements were recorded on the day of hospital discharge. Patients were followed for six months. The presence of major adverse cardiac events (MACE) (including all-cause mortality, recurrent ACS, requirement for revascularization, decompensated heart failure, cardiogenic pulmonary edema, atrial fibrillation, and stroke) in patients were recorded and the potential relationship between CA125 levels at hospitalization was evaluated [4,7,12].

To further evaluate the prognostic value of CA125, analyses were performed for both the composite MACE endpoint and its individual components. For this purpose, outcomes were categorized as any MACE, all-cause mortality, recurrent ACS, and other MACE.

The serum levels of CA125 were determined using a commercial electrochemiluminescence immunoassay kit (Roche® Diagnostics). The manufacturer’s cutoff value for CA125 is 35 KU/L.

2.4. Statistical analysis

Mean, standard deviation, frequency and percentage values were used in the descriptive statistics of the data. The distribution of variables was assessed using the Kolmogorov–Smirnov test. The independent samples t-test and Mann–Whitney U-test were used to analyze quantitative independent data. The chi-square test was used to analyze qualitative independent data, and the Fischer test was used when the chi-square test conditions were not met. The receiver operating characteristic (ROC) curve was used to determine the greatest area under the curve (AUC) and the optimal cutoff value in predicting MACE and related components. AUC values were compared using DeLong method. Univariable and multivariable regression analyses were used to identify potential independent predictors of MACE and related components. SPSS 28.0 software was used for the analyses. A p-value of less than 0.05 was considered statically significant.

3. Results

The mean age of the participants was 61.09 ± 10.87 years and 78.7 % of the patients were male. While 75.6 % of patients had at least one co-morbid disease, a family history of CVD was the most common cardiovascular (CV) risk factor (81.9 %). After six months of follow-up, 49 MACE (8 all-cause mortality, 28 recurrent ACS, 6 decompensated heart failure, 3 atrial fibrillation, 2 cardiogenic pulmonary edema, 1 requirement for revascularization, and 1 stroke) occurred in 33.9 % of the patients. No significant difference was detected in terms of systolic and diastolic blood pressure according to the presence of MACE (p > 0.05).

There was a statistically significant difference in age, number of comorbidities, number of CV risk factors, LVEF, CA125, hs-cTn, and proBNP according to the presence of MACE (p = 0.026, p < 0.001, p = 0.003, p = 0.004, p = 0.009, p = 0.014, p = 0.035, respectively). There was no statistically significant difference in MACE according to the type of ACS, hyperlipidemia (HL), obesity, diabetes mellitus (DM), smoking, alcohol use, family history of CVD, or the presence of stent (p > 0.05). There was a statistically significant difference in the occurrence of MACE according to gender, presence of comorbidity, and presence of hypertension (HT) (p = 0.007, p = 0.005, p = 0.001, respectively). The incidence of MACE was higher in females, patients with comorbidities, and patients with HT. Table 1 presents the clinical characteristics of the patients according to the presence of MACE.

Table 1.

Clinical characteristics of patients according to the presence of MACE.

	Total (n = 127)	Presence of MACE		a p
		No (n = 84)	Yes (n = 43)
	Mean ± SD	Mean ± SD	Mean ± SD
Age	61.09 ± 10.87	59.56 ± 11.29	64.09 ± 9.42	0.026*
Number of comorbidities	2.66 ± 2.1	2.20 ± 2.00	3.56 ± 2.03	<0.001*
Total number of CV risk factors	3.6 ± 1.43	3.33 ± 1.47	4.12 ± 1.22	0.003*
LVEF (%)	50.17 ± 10.84	52.12 ± 9.89	46.37 ± 11.69	0.004*
Systolic BP	146.93 ± 24.19	146.65 ± 25.17	147.47 ± 22.43	0.859
Diastolic BP	80.99 ± 14.75	80.79 ± 14.69	81.40 ± 15.03	0.827
CA125 (KU/L)	14.59 ± 20.28	10.03 ± 6.33	23.50 ± 32.12	0.009*
hs-cTn (ng/L)	316.69 ± 766.58	155.36 ± 271.33	631.83 ± 1209.85	0.014*
proBNP (ng/L)	2963.72 ± 6227.56	1927.72 ± 4048.78	4987.54 ± 8809.79	0.035*
	n (%)	n (%)	n (%)	b p
Gender				0.007*
Female	27 (21.3)	12 (44.4)	15 (55.6)
Male	100 (78.7)	72 (72)	28 (28)
Type of ACS				0.682
STEMI	38 (29.9)	23 (60.5)	15 (39.5)
NSTEMI	67 (52.8)	46 (68.7)	21 (31.3)
Unstable Angina	22 (17.3)	15 (68.2)	7 (31.8)
CV risk factors
Hypertension	79 (62.2)	44 (55.7)	35 (44.3)	0.001*
Hyperlipidemia	78 (61.4)	50 (64.1)	28 (35.9)	0.540
Obesity	32 (25.2)	19 (59.4)	13 (40.6)	0.350
Diabetes mellitus	42 (33.1)	23 (54.8)	19 (45.2)	0.057
Smoking	95 (74.8)	59 (62.1)	36 (37.9)	0.098
Alcohol use	28 (22)	19 (67.9)	9 (32.1)	0.828
Family history of CV disease	104 (81.9)	66 (63.5)	38 (36.5)	0.175

ACS: acute coronary syndrome, BP: blood pressure, CA125: carbohydrate antigen 125, CV: cardiovascular, hs-cTn: high sensitivity cardiac troponin, LVEF: left ventricular ejection fraction, MACE: major adverse cardiac events, NSTEMI: non-ST-elevation myocardial infarction, proBNP: pro–B-type natriuretic peptide, STEMI: ST-elevation myocardial infarction.

^*p < 0.05 statistically significant.

^aIndependent groups t test.

^bPearson chi-square test.

While the serum CA125 median value was 14.59 ± 20.28 in all patients, it was 23.50 ± 32.12 in the patients with MACE and was significantly higher (p = 0.009). No significant relationship was found between CA125 levels and age, number of comorbidities, number of CV risk factors, or systolic and diastolic blood pressure (p > 0.05). There was a positive, statistically significant relationship with CA125 and hs-cTn (r = 0.315, p < 0.001) and proBNP (r = 0.423, p < 0.001), and a negative relationship between LVEF (r = −0.186, p = 0.037) value. There was no statistically significant difference found in terms of CA125 levels according to gender, number of comorbidities, type of ACS, HT, HL, obesity, DM, smoking, alcohol use, family history of CVD, or the presence of a stent (p > 0.05). Table 2 presents the clinical characteristics of the patients according to CA125 levels.

Table 2.

Clinical characteristics of patients according to CA125 levels.

	CA125
	r	p
Age	0.118	0.185
Number of comorbidities	0.043	0.635
Total number of CV risk factors	0.085	0.344
LVEF (%)	−0.186	0.037*
Systolic BP	−0.109	0.221
Diastolic BP	−0.060	0.503
hs-cTn (ng/L)	0.315	<0.001*
proBNP (ng/L)	0.423	<0.001*
	Mean ± SD	a p
Gender		0.369
Female	19.67 ± 36.06
Male	13.22 ± 13.14
Comorbidity		0.795
No	15.42 ± 32.11
Yes	14.33 ± 14.81
Type of ACS		b0.401
STEMI	17.70 ± 30.33
NSTEMI	14.19 ± 15.49
Unstable Angina	10.44 ± 7.43
CV risk factor (Hypertension)		0.671
No	13.61 ± 26.04
Yes	15.19 ± 15.96
CV risk factor (Hyperlipidemia)		0.413
No	16.46 ± 27.24
Yes	13.42 ± 14.37
CV risk factor (Obesity)		0.455
No	13.81 ± 15.21
Yes	16.92 ± 31.01
CV risk factor (Diabetes mellitus)		0.821
No	14.30 ± 21.18
Yes	15.18 ± 18.55
CV risk factor (Smoking)		0.131
No	9.90 ± 5.83
Yes	16.17 ± 23.02
CV risk factor (Alcohol use)		0.569
No	14.04 ± 19.97
Yes	16.53 ± 21.57
CV risk factor (Family history of CV disease)		0.606
No	12.61 ± 9.18
Yes	15.03 ± 22.00
Presence of stent		0.963
No	14.49 ± 14.91
Yes	14.66 ± 23.29

ACS: acute coronary syndrome, BP: blood pressure, CA125: carbohydrate antigen 125, CV: cardiovascular, hs-cTn: high sensitivity cardiac troponin, LVEF: left ventricular ejection fraction, NSTEMI: non-ST-elevation myocardial infarction, proBNP: pro–B-type natriuretic peptide, SD: standard deviation, STEMI: ST-elevation myocardial infarction.

^*p < 0.05 statistically significant.

^aIndependent groups t test.

^bOne-way analysis of variance, r: Pearson correlation coefficient.

No statistically significant relationship was found between the number of CV risk factors and CA125, hs-cTn and proBNP (p > 0.05). A statistically significant but a weak negative relationship was found between the number of CV risk factors and LVEF (r = −0.194, p = 0.029) (Table 3).

Table 3.

Correlation of the study variables with the total number of cardiovascular risk factors.

	Total number of cardiovascular risk factors
	r	p
LVEF (%)	−0.194	0.029*
CA125 (KU/L)	0.085	0.344
hs-cTn (ng/L)	0.106	0.235
proBNP (ng/L)	0.024	0.786

CA125: carbohydrate antigen 125, hs-cTn: high sensitivity cardiac troponin, LVEF: left ventricular ejection fraction, proBNP: pro–B-type natriuretic peptide.

r: Pearson correlation coefficient,

^*p < 0.05 statistically significant.

In the ROC analysis performed to test the usability of CA125, hs-cTn, LVEF and proBNP values in predicting the presence of each individual component of MACE. CA125 had a statistically significant discriminatory ability for all individual MACE components except all-cause mortality. Table 4 presents the optimal cutoff values for the study variables and AUC, sensitivity, specificity, PPV, and NPV values with 95 % confidence intervals (CI).

Table 4.

AUC characteristics of the study variables.

	AUC (95% CI)	p	aCutoff	Sensitivity (95% CI)	Specificity (95% CI)	PPV (95% CI)	NPV (95% CI)
Any MACE
CA125	0.756 (0.667, 0.845)	<0.001*	>12.56	58.14 (42.1, 73.0)	84.52 (75.0, 91.5)	65.8 (48.6, 80.4)	79.8 (69.9, 87.6)
hs-cTn	0.674 (0.575, 0.774)	<0.001*	>0.2101	46.51 (31.2, 62.3)	80.95 (70.9, 88.7)	55.6 (42.0, 68.3)	74.7 (68.7, 79.9)
LVEF	0.644 (0.544, 0.745)	0.005*	≤59	74.42 (58.8, 86.5)	45.24 (34.3, 56.5)	41 (34.9, 47.5)	77.6 (66.3, 85.8)
proBNP	0.654 (0.551, 0.757)	0.003*	>1.735	51.16 (35.5, 66.7)	77.38 (67.0, 85.8)	53.7 (41.5, 65.4)	75.6 (69.1, 81.1)
All-cause mortality
CA125	0.684 (0.477, 0.892)	0.082	>15.5	62.5 (24.5, 91.5)	79.83 (71.5, 86.6)	17.2 (9.9, 28.4)	96.9 (92.8, 98.7)
hs-cTn	0.623 (0.402, 0.844)	0.246	>0.353	50 (15.7, 84.3)	82.35 (74.3, 88.7)	16 (7.9, 29.7)	96.1 (92.4, 98.0)
LVEF	0.600 (0.341, 0.859)	0.343	≤35	50 (15.7, 84.3)	86.55 (79.1, 92.1)	20 (9.8, 36.4)	96.3 (92.8, 98.1)
proBNP	0.686 (0.487, 0.885)	0.079	>3.342	62.5 (24.5, 91.5)	79.83 (71.5, 86.6)	17.2 (9.9, 28.4)	96.9 (92.8, 98.7)
Recurrent ACS
CA125	0.709 (0.621, 0.786)	<0.001*	>8.48	92.59 (75.7, 99.1)	48 (37.9, 58.2)	32.5 (27.9, 37.4)	96 (86.2, 98.9)
hs-cTn	0.620 (0.530, 0.705)	0.042*	>0.302	85.19 (66.3, 95.8)	37 (27.6, 47.2)	26.7 (22.7, 31.2)	90.2 (78.3, 95.9)
LVEF	0.552 (0.461, 0.640)	0.364	≤59	70.37 (49.8, 86.2)	41 (31.3, 51.3)	24.4 (19.4, 30.2)	83.7 (73.2, 90.6)
proBNP	0.565 (0.464, 0.643)	0.415	>2.024	44.44 (25.5, 64.7)	73 (63.2, 81.4)	30.8 (20.7, 43.0)	83 (77.3, 87.4)
Other MACE
CA125	0.677 (0.588, 0.757)	0.041*	>13.6	58.33 (27.7, 84.8)	76.52 (67.7, 83.9)	20.6 (12.7, 31.7)	94.6 (89.9, 97.2)
hs-cTn	0.726 (0.640, 0.801)	0.006*	>0.417	58.33 (27.7, 84.8)	87.83 (80.4, 93.2)	33.3 (20.1, 49.8)	95.3 (91.2, 97.5)
LVEF	0.708 (0.620, 0.785)	0.010*	≤45	75 (42.8, 94.5)	63.48 (54.0, 72.3)	17.6 (12.5, 24.3)	96.1 (90.0, 98.5)
proBNP	0.728 (0.641, 0.803)	<0.001*	>0.433	100 (73.5, 100.0)	45.22 (35.9, 54.8)	16 (13.9, 18.4)	100 (94.3, 100.0)

AUC: area under the curve, CI: confidence interval, CA125: carbohydrate antigen 125, hs-cTn: high sensitivity cardiac troponin, LVEF: left ventricular ejection fraction, MACE: major adverse cardiac events, NPV: negative predictive value, PPV: positive predictive value, proBNP: pro–B-type natriuretic peptide.

^*p < 0.05 is statistically significant.

^aCutoff values were determined according to the Youden index.

ROC curves for the biomarkers and LVEF were compared using the DeLong method. For the recurrent ACS outcome, the AUC for CA125 was statistically significantly greater than that for LVEF and proBNP (p = 0.023 and p = 0.010, respectively). No statistically significant differences were observed among the remaining AUCs (p > 0.05) (Table 5).

Table 5.

Comparison of ROC curves for biomarkers and LVEF.

	Any MACE	All-cause mortality	Recurrent ACS	Other MACE
CA125 vs hs-cTn	0.202	0.733	0.195	0.580
CA125 vs LVEF	0.063	0.493	0.023*	0.739
CA125 vs proBNP	0.061	0.987	0.010*	0.503

CA125: carbohydrate antigen 125, hs-cTn: high sensitivity cardiac troponin, LVEF: left ventricular ejection fraction, MACE: major adverse cardiac events, proBNP: pro–B-type natriuretic peptide.

DeLong method,

^*p < 0.05 is statistically significant.

To identify independent predictors of MACE and its components, univariable and multivariable logistic regression analyses were performed. Multivariable logistic regression analyses were conducted including variables that were significant in univariable analyses, along with CA125, hs-cTn, LVEF, and proBNP irrespective of their univariable significance. Backward elimination was used for model selection. CA125, hs-cTn, LVEF, and proBNP were entered as categorical variables based on predefined cutoff values for each MACE component, and results were expressed as odds ratios (ORs) with 95 % CI.

In univariable analysis, CA125 categorized by the predefined cutoff value was significantly associated with the occurrence of any MACE (OR 7.585, 95 % CI 3.253–17.686; p < 0.001). This association remained significant in multivariable logistic regression analysis after adjustment for relevant covariates (OR 8.527, 95 % CI 3.355–21.673; p < 0.001), indicating an independent association with the occurrence of any MACE. CA125 also remained independently associated with the occurrence of all individual MACE components in multivariable analyses, with statistically significant results across all outcomes (p < 0.05) (Supplementary Table 1 (https://www.j-saudi-heart.com/cgi/editor.cgi?window=additional_files&article=1478&context=jsha) and Supplementary Table 2 (https://www.j-saudi-heart.com/cgi/editor.cgi?window=additional_files&article=1478&context=jsha)).

4. Discussion

CA125 is a glycoprotein belonging to the mucin family. It is produced by mesothelial cells in the pericardium, pleura, peritoneum, and Müllerian epithelium, possibly in response to mechanical (occlusion) or inflammatory stress [6]. Numerous studies investigated the prognostic role of elevated CA125 levels in various heart diseases [5–7,12–23]. The breakdown of CA125 reveals the following characteristics that make it a promising prognostic tool in ACS: it is readily available and more cost-effective than other biomarkers, and it is a stable molecule with a prolonged half-life (>1 week). This extended half-life enables its association with the disease’s clinical status and prognosis, enhancing its value in predicting patients at high risk of adverse outcomes [7].

The average CA125 level in patients diagnosed with ACS was 12.56 U/mL. Previous studies have shown that CA125 levels range from 12 to 24 U/mL in patients with ACS [12,14,15]. Additionally, another study reported an average CA125 value of 13.85 U/mL in their investigation of the association between CA125 levels and mortality in female patients with ACS [18]. In a study that assessed the predictive value of CA125 levels for PCI outcomes after ACS in male patients, the reported CA125 level in ACS patients was 7.99 U/mL [7]. Although our study found higher CA125 levels in female patients than in male patients, this difference was not statistically significant (19.67 vs. 13.22 U/mL).

Falcao et al. [4] identified 11.48 IU/mL as the optimal CA125 cutoff value, whereas Luo et al. [18] reported it as 16.4 U/mL. In our study, the threshold for MACE development was determined to be 12.56 U/mL.

Separham et al. [7] demonstrated that patients with ACS who later developed MACE had significantly elevated CA125 and cardiac troponin I levels and a notably lower LVEF. Their study also confirmed the role of CA125 level as an independent predictor for MACE onset, with an average CA125 level of 18.92 U/mL in patients who experienced MACE. In another study, Falcao et al. [4] reported an average CA125 value of 9.2 U/mL among patients with high mortality rates, emphasizing the strong statistical correlation between CA125 and mortality. Additionally, we observed significantly increased levels of CA125, proBNP, and hs-cTn in the group that experienced MACE during the 6-month follow-up, with CA125 levels measured at 23.50 U/L in this cohort. These findings are aligned with the existing literature, which also suggests that patients experiencing MACE have higher CA125 levels.

Falcao et al. [4] found that HT (74.4 %), smoking (45.4 %), and DM (34.9 %) were significant risk factors for mortality in patients with ACS. However, our study observed a different order of prevalence for these factors in MACE cases: HT (44.3 %), DM (45.2 %), and obesity (40.6 %).

A previous study reported that CA125 demonstrated ROC performance comparable to NT-proBNP and hs-CRP in predicting all-cause mortality in patients with STEMI, suggesting its potential use alongside or as an alternative to established biomarkers [4]. In the present study, CA125, hs-cTn, and proBNP were associated with the occurrence of any MACE but not with all-cause mortality, and significant positive correlations were observed among these biomarkers. These findings suggest that CA125 may contribute to early risk stratification in patients with ACS. Nevertheless, further studies with more precise discrimination of individual MACE components are warranted.

Impaired left ventricular function often follows ACS and frequently leads to heart failure, resulting in subsequent hospital readmissions. Duman et al. [13] found elevated CA125 levels in patients with symptomatic advanced mitral stenosis, even when their LVEF and left ventricular dimensions were within the normal range. This discovery may offer insights into the physiological factors that trigger CA125 production in patients with ACS who later develop heart failure. Yalta et al. [14] reported a substantial increase in CA125 levels and an inverse relationship between CA125 and LVEF in patients with ACS with a LVEF below 55 %. Similarly, Luo et al. [18] identified higher CA125 levels in patients with ACS experiencing acute heart failure during hospitalization, with a weak negative correlation with LVEF values. In another study, Kouris et al. [24] found elevated CA125 levels in patients with ACS and decompensated heart failure, particularly in those with pulmonary congestion and peripheral edema. Our study also demonstrated a weak negative correlation between CA125 levels and LVEF values (r = −0.186) in patients with ACS. These findings may suggest that patients with ACS with elevated CA125 levels may have an increased risk of hospitalizations related to heart failure. However, differences in the magnitude of the correlation coefficients suggest the need for further investigations.

De Gennaro et al. [15] measured CA125 and BNP levels in patients with ACS within the first 24 h and 72 h after hospitalization and reported higher CA125 and BNP levels. In the same study, it was reported that CA125 levels alone have higher specificity and sensitivity than BNP levels in predicting the incidence of acute heart failure. In the present study, acute heart failure was not evaluated as an individual MACE component; however, CA125 and proBNP levels were significantly higher in patients who developed any MACE.

Female gender was found to be associated with an over fourfold higher risk of MACE compared with males. The first episode of ACS is reported to occur nearly 10 years later in women than in men, and women tend to have a higher burden of CV risk factors [25–27]. In our study population, despite a female-to-male ratio of approximately 1:4, the incidence of MACE was higher among women than men (56 % vs. 28 %, respectively). These findings are broadly consistent with existing evidence and further highlight gender-related differences in clinical outcomes after ACS.

4.1. Limitations

This prospective cohort study was conducted in a single center and included a small number of patients. This may limit the results’ adaptation to all populations. Additionally, the biomarkers evaluated in the study were measured only with samples obtained during hospitalization, and these values may vary from symptom onset to time. Therefore, serial measurements will allow more precise prognostic data to be provided. Other factors that may allow patients to develop MACE in the post-discharge period (e.g., type of stent, access to treatment, and patient adherence) are not included in our analyses and cannot be ignored. Finally, the follow-up period of our study was limited to 6 months. A longer follow-up of patients for MACE after discharge may also determine a more precise relationship with survival rates.

5. Conclusions

Our study results showed a potential association between increased CA125 levels in patients diagnosed with ACS and the risk of developing MACE at a 6-month follow-up after discharge. At the same time, it can be concluded that CA125 has a similar predictive value to other cardiac parameters (hs-cTn, LVEF, and proBNP) in terms of MACE development. The factors affecting the occurrence of MACE are CA125 levels, female gender, and number of CV risk factors.

Abbreviation list

ACS

Acute Coronary Syndrome

CA125

Carbohydrate Antigen 125

CAD

Coronary Artery Disease

CVD

Cardiovascular diseases

DM

Diabetes Mellitus

hs-CRP

High-sensitivity C Reactive Protein

hs-cTn

High-sensitivity Cardiac Troponin

HL

Hyperlipidemia

HT

Hypertension

LVEF

Left Ventricular Ejection Fraction

MACE

Major Adverse Cardiac Events

NSTEMI

Non-ST-Elevation Myocardial Infarction

PCI

Percutaneous Coronary Intervention

proBNP

Pro–B-type Natriuretic Peptide

STEMI

ST-Elevation Myocardial Infarction

UA

Unstable Angina

Data availability

Data is available from the corresponding author on a reasonable request.