Highlights
- Combining CA125 and NT-proBNP markedly improves risk prediction for cardiovascular mortality, all-cause mortality, and rehospitalization in acute heart failure (AHF).
- High levels of both biomarkers identify patients at substantially elevated risk, supporting their joint use in clinical decision-making.
- This prospective Vietnamese cohort provides region-specific evidence for biomarker-guided management in AHF.
Study Background and Disease Burden
Acute heart failure (AHF) remains a major driver of morbidity, mortality, and healthcare resource utilization worldwide, with Southeast Asia—Vietnam in particular—witnessing a rising burden due to demographic shifts and increased cardiovascular risk factors. Despite therapeutic advancements, early risk stratification to guide personalized management is a persistent unmet need. Biomarkers have become indispensable for diagnosis and prognosis in AHF, with N-terminal pro-B-type natriuretic peptide (NT-proBNP) established as a gold standard. However, its specificity and prognostic power are imperfect, prompting active research into complementary biomarkers.
Carbohydrate antigen 125 (CA125), long recognized as a tumor marker (particularly for ovarian carcinoma), has recently emerged as a potential marker for congestion and inflammatory activity in heart failure. Elevated CA125 levels reflect serosal inflammation and fluid overload, both central to AHF pathophysiology. Yet, data on its additive value to NT-proBNP, especially in Asian populations, remain limited.
Study Design
This prospective observational cohort study was conducted at multiple Vietnamese centers, enrolling 316 adult patients admitted with a diagnosis of AHF. At the time of first admission, blood samples were obtained for measurement of both CA125 and NT-proBNP. Patients were subsequently followed for 12 months, with outcomes including cardiovascular mortality, all-cause mortality, and a composite of all-cause mortality or rehospitalization due to heart failure systematically recorded. Multivariate Cox regression analyses adjusted for relevant clinical covariates were used to evaluate the prognostic significance of biomarker levels, both singly and in combination.
Key Findings
During the 12-month follow-up, 38 patients (12.0%) died of cardiovascular causes, 81 patients (25.6%) died from any cause, and 145 patients (45.9%) experienced the composite endpoint of all-cause death or heart failure rehospitalization. The study’s most compelling finding is the dramatic increase in adverse outcomes among patients with both high CA125 and high NT-proBNP levels at presentation:
- Cardiovascular mortality: adjusted Hazard Ratio (aHR) = 11.77 (95% CI: 3.73–37.09, p < 0.001)
- All-cause mortality: aHR = 4.53 (95% CI: 1.99–10.28, p < 0.001)
- Composite outcome: aHR = 6.02 (95% CI: 2.75–13.24, p < 0.001)
These effect sizes indicate that patients with elevated levels of both biomarkers face an 11-fold higher risk of cardiovascular death and a 6-fold higher risk of major adverse events compared with lower-risk counterparts. The incremental prognostic value of CA125, when added to NT-proBNP, was statistically significant, improving the model’s predictive accuracy beyond NT-proBNP alone.
Notably, this study did not identify significant safety concerns associated with biomarker testing, as both are non-invasive, widely available blood measurements. The relatively high event rates underscore the severity of AHF in this population and highlight the urgent need for improved risk stratification.
Expert Commentary
Current clinical guidelines (e.g., European Society of Cardiology, 2023; American Heart Association, 2022) endorse natriuretic peptides as central to AHF evaluation, but emphasize the need for multimodal risk assessment. The findings by Truong et al. align with emerging international evidence (see Núñez et al., J Am Coll Cardiol, 2016) supporting CA125 as a marker of congestion and inflammation, relevant to both pathophysiology and prognosis in heart failure.
The robust hazard ratios seen in this prospective Vietnamese cohort underscore the generalizability of CA125’s prognostic value across diverse populations. Mechanistically, CA125 is secreted by mesothelial cells in response to serosal irritation or volume overload, conditions prevalent in AHF. Combining CA125 with NT-proBNP—which reflects myocardial stretch and neurohormonal activation—yields a more holistic risk profile, potentially informing therapeutic escalation, discharge planning, and outpatient follow-up.
Limitations of this study include its single-country context (potentially affecting external validity), lack of granular detail on therapeutic interventions, and the absence of serial biomarker measurements. Nonetheless, these data fill an important regional evidence gap and may support broader adoption of CA125 in heart failure risk algorithms.
Conclusion
The combination of CA125 and NT-proBNP provides robust and clinically meaningful prognostic information in patients admitted with acute heart failure, effectively identifying individuals at highest risk for cardiovascular death, all-cause mortality, and rehospitalization. These findings support the integration of CA125 into routine risk assessment protocols alongside NT-proBNP, particularly in resource-constrained settings where maximizing the predictive value of available tests is essential. Future research should explore serial biomarker dynamics and assess whether biomarker-guided management can improve patient outcomes.
References
1. Truong CM, Do NHN, Chau HN, Thai TT. Prognostic value of carbohydrate antigen 125 combined with N-terminal pro B-type natriuretic peptide in patients with acute heart failure: a prospective cohort study in Vietnam. BMC Cardiovasc Disord. 2025 Jul 18;25(1):523. doi: 10.1186/s12872-025-04994-0. PMID: 40681999; PMCID: PMC12273334.
2. Núñez J, et al. CA125 and congestive heart failure: additional insights. J Am Coll Cardiol. 2016;68(20):2320-2331.
3. McDonagh TA, et al. 2023 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J. 2023;44(33):3227–3337.
4. American Heart Association. 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure. J Am Coll Cardiol. 2022;79(17):e263–e421.
