Citokine networks and heart failure outcomes: CA125 as a bridge between congestion and inflammation
J Montiel Perez, E Santas, A Marti-Martinez, S Villar, R De La Espriella, E Rodriguez-Borja, E Revuelta-Lopez, A Gonzalez-Miqueo, A Bayes-Genis, J Sanchis, J NunezAbstract
Aims
Inflammation and congestion are key pathophysiological processes in heart failure (HF). Carbohydrate Antigen 125 (CA125) is a well-established biomarker in HF, primarily associated with congestion, but also it may act as a functional ligand amplifying the inflammatory response in HF. Our aim was to evaluate the potential modulatory effect of CA125 on inflammation, assessed by a set of cytokines (interleukin [IL]-6, IL-10, IL-1β, and tumor necrosis factor [TNF]-α).
Methods
We prospectively included 284 patients admitted for acute HF in which cytokines and CA125 were assessed at admission. Study endpoints were all-cause mortality and total HF rehospitalizations.
The association between biomarkers and all-cause mortality was evaluated using a Cox regression analysis. For the readmission endpoint, negative binomial regression models were employed to simultaneously analyze the number of HF readmissions (as counts) and all-cause mortality (as a terminal event).
Results
At a median follow-up of 4.2 years (interquartile range: 1.3 – 7.5), a total of 211 patients (74.3 %) died, and 117 patients (41.2 %) experienced 249 HF readmissions. In the multivariable analysis, a significant interaction between IL-6 and IL-10 and CA125 was observed for both outcomes (p-value for interactions < 0.05 for all comparisons). Among patients with CA125 > 35 U/mL, both IL-6 and IL-10 showed a positive, linear relationship with the risk of death or HF readmissions. In contrast, we did not find a significant association in patients with CA125 ≤ 35 U/mL.
Conclusions
In conclusion, the association between IL-6 and IL-10 with long-term adverse events was significantly modulated by CA125 status, being significantly associated with poor prognosis only when CA125 was upregulated. These findings support a potential modulatory role for CA125 in the inflammatory response in HF.Mortality risk modified by CA125For image description, please refer to the figure legend and surrounding text.HF readmissions modified by CA125For image description, please refer to the figure legend and surrounding text.