Chronic heart failure (CHF) is the terminal manifestation of all cardiovascular diseases and the main cause of death. It is an increasingly serious public health problem facing the clinic and society. The incidence of chronic heart failure in China has been increasing year by year. Currently, the number of people suffering from heart failure in my country has reached 8.9 million, and the number of deaths from cardiovascular diseases accounts for 45.5% of the total number of deaths
[1]
.
B-type natriurctic peptide (BNP) is the most widely used biomarker of heart failure. It is related to the increase in ventricular pressure and load. Due to its limitations, its predictive effect on adverse cardiovascular events is unsatisfactory
[2]
. Antigen carbohydrate 125 (CA125) is highly expressed in ovarian and metastatic malignant tumors, it has been found to be associated with mechanical stress and inflammatory response caused by serous effusion, with a half-life of 4.8 days
[3]
. Studies have shown that CA125 is closely related to cardiac function and hemodynamic parameters, and plays an effective role in predicting adverse cardiovascular events
[4]
. Exploring the relationship between CA125, BNP and cardiac function can further enhance the prediction, treatment and prognosis of heart failure
[5]
.
This study mainly analyzed the expression of CA125 in the serum of CHF patients, the relationship between CA125 levels and the occurrence of adverse cardiovascular events, and explained the role of CA125 in predicting adverse cardiovascular events in patients with chronic heart failure.
2. Materials and Methods2.1. General Information
Clinical data of CHF patients admitted to our hospital from January 2023 to December 2023 were collected. 1) Inclusion criteria: The diagnostic criteria for heart failure refer to the fourth edition of Practical Cardiology edited by Chen Haozhu, using the modified Framingham heart failure diagnostic criteria, and the classification of heart failure uses the NYHA heart function classification standard of the New York Heart Association. 2) Exclusion criteria: Patients with acute coronary syndrome, acute infection, tuberculosis, tumors, severe liver and kidney diseases, and surgical trauma in the past three months.
A total of 132 CHF patients were included and divided into heart function II group (46 cases), heart function III group (42 cases), heart function IV group (44 cases) according to heart function. Another 44 healthy subjects who underwent physical examination during the same period were selected as the control group. The general information is no significant difference between the groups (P > 0.05), which was comparable (
Table 1
).
2.2. Method
The clinical baseline data of the patients were collected and fasting venous blood was collected to measure the levels of CA125, NT-proBNP, CA199, CEA, and
<xref ref-type="bibr" rid="scirp.135282-"></xref>Table 1. Comparison of general clinical data among different groups.
Control Group
NYHA II
NYHA III
NYHA IV
Quantity
44
46
42
44
Age
70.52 ± 8.92
69.13 ± 8.27
70.45 ± 9.33
69.25 ± 7.37
Gender (male/female)
20/24
24/22
21/21
21/23
Basic heart disease
coronary heart disease
30
22
25
Hypertensive heart disease
4
6
4
Valvular heart disease
6
8
4
Dilated cardiomyopathy
0
4
5
Restrictive cardiomyopathy
0
2
3
Other
6
2
3
Treatment
ACEI/ARB/ARNI
40/46 (87%)
35/42 (83%)
32/44 (73%)
MRA
40/46 (87%)
36/42 (86%)
40/44 (91%)
B-blocker
32/46 (70%)
36/42 (86%)
35/44 (80%)
SGLT-2inhibitor
30/46 (65%)
33/42 (79%)
39/44 (89%)
Diuretic
33/46 (72%)
40/42 (95%)
43/44 (98%)
AFP. Echocardiography was performed to measure LVEDD and LVEF. All CHF patients were discharged after receiving standardized drug treatment. After discharge, the two groups of patients were followed up for 12 months by telephone and outpatient visits to observe the incidence of major adverse cardiovascular events 12 months after treatment, with the main indicators being the rate of re-hospitalization and mortality.
Blood samples were collected from all patients or their families after informed consent, and the blood sample collection and experimental process were approved by the Medical Ethics Committee of Shizuishan Second People’s Hospital.
2.3. Statistical Method
SPSS 23.0 was used for statistical analysis. The measurement data were expressed as (mean ± standard deviation). The t test was used for comparison between groups, and the variance test was used for comparison between multiple groups. The count data were expressed as [n (%)] and compared with the χ2 test. The influencing factors were analyzed by multivariate logistic regression, and the test level was α = 0.05.
3. Result3.1. Comparison of Four Groups of CA125, CA199, CEA, AFP, LVEF, and LVEDD
Compared with the control group, the differences in CA125, NT-proBNP, LVEDD, and LVEF in the CHF group were statistically significant (P < 0.05), and were related to the cardiac function level of CHF patients. Among them, LVEF was negatively correlated with the cardiac function grade, and CA125, BNP and LVEDD levels were positively correlated with cardiac function classification, and the results were statistically significant (P < 0.05). There was no significant difference in CA199, CEA, and AFP levels (P > 0.05) (
Table 2
).
<xref ref-type="bibr" rid="scirp.135282-"></xref>Table 2. Comparison of four groups of CA125, CA199, CEA, AFP, LVEF, and LVEDD.
Control Group
NYHA II
NYHA III
NYHA IV
NT-proBNP
188.11 ± 152.59
983.46 ± 934.31a
4192.86 ± 1969.22ab
10,212.92 ± 5721.89abc
CA125
9.21 ± 2.64
16.96 ± 11.31a
60.04 ± 80.91ab
205.39 ± 171.15abc
CA199
8.43 ± 3.89
8.12 ± 2.97
8 ± 3.09
8.59 ± 3.22
AFP
3.27 ± 1.04
3.54 ± 2.03
4.4 ± 4.25
3.52 ± 1.82
CEA
2.17 ± 1.24
2.09 ± 1.38
2.13 ± 1.2
2.55 ± 1.18
LVEDD
45.47 ± 2.49
49.62 ± 3.9a
54.61 ± 6.53ab
70.56 ± 6.83abc
LVEF
67.45 ± 5.18
55.04 ± 10.87a
48.69 ± 7.81ab
40.07 ± 7.44abc
Note: aRepresents a statistically significant difference compared to the control group, P < 0.05; bRepresents a statistically significant difference compared to the NYHA II group, P < 0.05; cRepresents a statistically significant difference compared to the NYHA III group, P < 0.05.
3.2. Analysis of CA125 Serum Level and Rehospitalization Rate and Mortality Rate of Patients
All subjects were followed up for 12 months, and a total of 8 deaths and 20 readmissions were reported in the 132 patients. The patients were divided into two groups according to whether the serum CA125 concentration was greater than 35 U/ml. The mortality rate and readmission rate of the group with a serum concentration greater than 35 U/ml were significantly increased, with a statistically significant difference (P < 0.05), indicating that as the CA125 level increases, the readmission rate and mortality rate of CHF patients also increase (
Table 3
).
3.3. Correlation Analysis of CA125 with LVEDD, LVEF, NT proBNP
CA125 is positively correlated with NT proBNP (P < 0.001), positively correlated with LVEDD (P < 0.001), and negatively correlated with LVEF (P < 0.001) (
Figure 1
).
4. Discussion
CA125 is a membrane-associated mucin that is mainly synthesized in mesothelial cells and is often used for the detection, prognosis and recurrence monitoring of ovarian cancer
[6]
. In patients with heart failure, increased interstitial venous
<xref ref-type="bibr" rid="scirp.135282-"></xref>Table 3. Analysis of CA125 serum level and rehospitalization rate and mortality rate of patients.
CA125 serum level
Total
Number of deaths
mortality rate
Number of readmissions
re-hospitalization rate
>35
67
8
8/67 (11.9%)*
20
20/67 (29.9%)#
≤35
65
0
0 (0%)
6
6/65 (9.2%)
Note: *Indicates that the mortality rate was statistically different from that of the group with serum CA125 concentration < 35 U/ml, P < 0.05; #Indicates that the readmission rate was statistically different from that of the group with serum CA125 concentration < 35 U/ml, P < 0.05.
Figure 1. Correlation analysis of CA125 with LVEDD, LVEF, NT proBNP.
pressure and inflammatory stimulation cause mesothelial cell damage, which promotes the synthesis of CA125 in the pleural cavity. At the same time, macrophages are activated, which promotes the binding of CA125 to galectin 3 (Gal-3) pentamer, and acts on the fibroblast membrane through Gal-3 ligand, further leading to increased myocardial fibrosis and cardiac remodeling through inflammatory and fibrotic pathways
[4]
[7]
[8]
. In recent years, the inflammatory response associated with heart failure has gradually received attention
[2]
. It has been found that the levels of multiple inflammatory factors in the serum of CHF patients are increased
[9]
. Among them, the inflammatory factors IL-1β and TNF-α can promote the secretion of CA125. It is currently believed that CA125 is related to myocardial mechanical pressure and inflammatory factors in heart failure
[10]
[11]
.
Our study showed that serum CA125 was associated with the severity of heart failure. As heart failure worsened and cardiac function declined, the serum CA125 level increased, which was consistent with previous studies
[12]
[13]
, suggesting that CA125 can be used as an indicator to reflect the severity of heart failure.
Nunez et al. found that in AHF patients, CA125 was an independent predictor of mortality at 6 months, and high CA125 levels may be associated with increased all-cause mortality and re-hospitalization for heart failure
[4]
. This study followed up the patients for 12 months, and the results showed that CHF patients with CA125 > 35 U/ml had a higher mortality rate (11.9%) and re-hospi- talization rate (29.9%). This suggests that CA125 can be used as a prognostic monitoring indicator for CHF patients.
5. Conclusion
The results of this study showed that serum CA125 levels are related to the cardiac function level of patients with chronic heart failure, and increase with the worsening of cardiac function. It can be used as an indicator of the severity of heart failure. It is not related to the cause of CHF, and is positively correlated with NT-proBNP and LVEDD, and negatively correlated with LVEF. In the study of prognosis, although our results show the important role of CA125 in the diagnosis and treatment of heart failure and prognosis, a larger sample size and longer follow-up time are still needed to verify the results so that they are more reliable.
Funding
This work was supported by Ningxia Medical University University-level Scientific Research (No. XM2022174).
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