Carbohydrate antigen 125 and clinical outcomes in heart failure: systematic review and meta-analysis.

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; I = 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; I = 39.6%) and chronic heart failure (CHF) (HR based on seven studies: 2.52, 95% CI 1.69-3.77; p < 0.01; I = 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; I = 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.