Our study compared the risk prediction capacity of NTproBNP and CA125 in the setting of AHF. After multivariate adjustment, elevation of CA125 and NTproBNP had negative prognostic effect on event-free survival. Not only elevated NTproBNP but also CA125 remained independent predictors of poor outcomes by combined both biomarkers. Additionally, adding CA125 in the model including NTproBNP significantly improved predictive power.
Congestion as a strong predictor of heart failure-related readmission and death20, being responsible for most of heart failure decompensation, is an important therapeutic target in AHF17,18; however, evaluation of congestion remains a challenge in the routine management of AHF21. Perhaps the limited accuracy of signs and symptoms for quantifying fluid overload severity22,23, signs of congestion (peripheral oedema, pleural effusion and so on) are not routinely used for risk stratification. Suitable biomarkers would optimize risk prediction. CA125 levels correlate well with signs of fluid congestion9,10,16 and pulmonary artery wedge pressure10,16. In this study, the most important clinical predictor of serum CA125 levels was the presence of pleural effusion. As a marker of congestion, CA125 being related with adverse events in heart failure patients9,10, has been shown to be indicative as a heart failure severity surrogate. Elevated CA125 is an independent predictor with incremental prognostic value over traditional prognosticators and natriuretic peptides9, and thus, combining both biomarkers improved risk stratification in AHF10.
Interestingly, although CA125 has shown to be a potential tool for treatment guiding in AHF12,24, little support is available regarding the benefits of NP-guided therapy over usual care25. In the CHANCE-HF trial, compared to the standard of care, a CA125-guided therapy characterized by a higher frequency of furosemide equivalent dose adjustments and ambulatory intravenous furosemide administrations according to CA125 response and clinical profile indicated a significantly reduced risk of 1-year mortality or AHF readmission12. In a recent multicenter randomized study of 160 AHF subjects with renal dysfunction, a CA125-guided diuretic strategy with admission loop diuretics dose determined on the basis of CA125 levels significantly improved 72-h eGFR24. Briefly, in subjects with high CA125 levels, high-intensity diuretic treatment and/or closer follow-up were advocated. When CA125 was low or decreased, a down-titration was recommended in both trials which endorsed the role of CA125-guided decongestion treatment in AHF.
Given CA125's long half-life (around 5–12 days)16, and a shorter mean half-life of NTproBNP (60–120 min)26, CA125 potentially provides pathophysiological information several weeks prior and NTproBNP could provide acute haemodynamic information, being similar to glycated hemoglobin and serum glucose in diabetes. One study reported that levels of CA125 and NTproBNP represent distinct pathophysiological states related to heart failure severity10. The combined use of CA125 and NTproBNP improved risk stratification and this multi-marker approach hold promise in guiding depletive therapy, showing the need to incorporate CA125 into clinical daily practice. In addition, conversely to natriuretic peptides, age, gender, body weight and renal function did not significantly influence CA125 levels12,21. In current study, we found that NTproBNP strongly depended on serum creatinine, weight, and LVEF, while CA125 appeared not to be significantly influenced by other factors which are highly prevalent. Beyond these considerations, additional benefits for implementing CA125 testing in daily clinical practice arise from its standardized measurement, low cost, and wide availability.
Our study had some limitations. Firstly, its observational design makes it susceptible to confounding factors and bias. Secondly, it is a single-center study which precludes extrapolation of results. Thirdly, it is not possible to extrapolate findings to patients undergoing renal dialysis because this study included patients with baseline serum creatinine values ≤ 360 umol/L. Finally, we measured CA125 levels at onetime point after an overnight fast on the second day of admission; however, peak CA125 levels might better reflect fluid overload in patients with AHF.