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Carbohydrate antigen 125 and clinical outcomes in heart failure: systematic review and meta-analysis
Seyed Morteza Pourfaraji1, Fatemeh Ojaghi Shirmard1, Dorsa Salabat1
1Cardiovascular Diseases Research Institute, Tehran Heart Center, Tehran University of Medical Sciences, Tehran, Iran.
Insights
Elevated Carbohydrate Antigen 125 (CA125) levels are linked to increased mortality and hospitalization risks in heart failure (HF) patients. CA125 serves as a valuable, non-invasive tool for assessing HF severity and treatment response.
Area of Science:
- Cardiology
- Biomarker Research
- Clinical Outcomes Analysis
Background:
- Carbohydrate Antigen 125 (CA125) is a potential biomarker for heart failure (HF).
- Existing research suggests an association between CA125 levels and HF prognosis.
- A comprehensive evaluation across diverse HF populations is needed.
Purpose of the Study:
- To conduct a meta-analysis evaluating the association between CA125 levels and clinical outcomes in heart failure patients.
- To assess CA125 as a prognostic factor for mortality and hospitalization in HF.
- To explore CA125's utility in disease severity assessment and therapy monitoring.
Main Methods:
- Systematic literature search of PubMed, Scopus, Web of Science, and Embase up to April 2025.
- Meta-analysis of 29 studies including 20,458 patients, using random-effects and Hartung-Knapp-Sidik-Jonkman models.
- PRISMA guidelines followed; study registered in PROSPERO (CRD420251023141).
Main Results:
- Higher CA125 levels significantly increased the risk of endpoint events (death or HF hospitalization) (HR 2.23).
- This increased risk was consistent in both acute (HR 1.88) and chronic (HR 2.52) heart failure subgroups.
- A significant direct correlation was found between CA125 and pro-BNP levels (r=0.42).
Conclusions:
- CA125 is a significant prognostic factor for mortality and hospitalization in heart failure.
- CA125 can serve as a non-invasive, operator-independent tool for evaluating disease severity and monitoring treatment response.
- Further research is recommended to establish optimal CA125 cut-off levels for HF management, particularly for guiding diuretic therapy.
Introduction:
Carbohydrate Antigen 125 (CA125) has emerged as a potential biomarker in patients with heart failure (HF). This meta-analysis comprehensively evaluates the association between CA125 levels and clinical outcomes across HF populations.
Methods:
We conducted this study based on the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA). We systematically searched PubMed, Scopus, Web of Science, and Embase libraries up to April 2025. We selected the original English-language investigations that reported the association between CA125 levels and clinical outcomes in cases with HF. The random-effects model and Hartung-Knapp-Sidik-Jonkman method were used to pool effect sizes and report summary statistics. The current review was registered in PROSPERO (CRD420251023141).
Results:
A total of 20,458 cases were included from 29 studies, with an average age of 70.3 years, and 36.1% of cases were women. The average cut-off level was 37.78 U/mL, and 35 U/mL was mainly used as the CA125 cut-off level. A meta-analysis of nine studies that reported the risk of experiencing endpoint events (death or HF-related hospitalization) showed significantly higher risk (HR 2.23, 95% CI 1.69-2.93; p < 0.01; I2 = 75.0%) among the patients with higher CA125 levels compared to those with lower levels. The increased risk remained significant across the acute heart failure (AHF) (HR based on two studies: 1.88, 95% CI 1.54-2.30; p < 0.01; I2 = 39.6%) and chronic heart failure (CHF) (HR based on seven studies: 2.52, 95% CI 1.69-3.77; p < 0.01; I2 = 77.4%) subgroups. Furthermore, a correlation meta-analysis of 13 studies revealed a significant direct correlation between CA125 and pro-BNP levels (r = 0.42; 95% CI 0.30 to 0.54; p < 0.01; I2 = 96.9%).
Conclusion:
The current review findings revealed CA125 as a significant prognostic factor of mortality and hospitalization risks in HF population. Furthermore, CA125 could be a non-invasive and operator-independent tool for evaluating disease severity and monitoring response to therapy. We suggested CA125 for monitoring various treatments in individuals with HF, specifically diuretic therapy. Further prospective studies are needed to determine the optimal cut-off for CA125 levels in HF.
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