Modulating Effect of Carbohydrate Antigen 125 on the Prognostic Value of High-Sensitivity C-Reactive Protein in Heart Failure

Inflammation and congestion are key pathophysiological processes in heart failure (HF). Our aim was to evaluate the potential modulatory effect of carbohydrate antigen 125 (CA125) on inflammation, assessed by high-sensitivity C-reactive protein (hs-CRP). We analyzed a cohort of 4043 consecutive patients in whom hs-CRP and CA125 levels were measured during a hospitalization for acute HF. Multivariate Cox regression models were applied to assess the association between the biomarkers and all-cause mortality and death/HF rehospitalization at 6 months. In multivariable analysis, a significant interaction between hs-CRP and CA125 was observed for both outcomes (<i>p</i>-value for interaction = 0.036 and <0.001, respectively). hs-CRP was significantly associated with an increased risk of death (HR = 1.27; 95% CI 1.16-1.41; <i>p</i> < 0.001) and death/HF rehospitalization (HR = 1.18; 95% CI 1.09-1.28; <i>p</i> < 0.001) if CA125 > 35 U/mL. In contrast, hs-CRP was not predictive of events when CA125 ≤ 35 U/mL. In conclusion, in patients with acute HF, the association between hs-CRP and clinical outcomes was modulated by CA125 levels. hs-CRP was associated with a higher risk of events only in patients with elevated CA125. These findings support a potential modulatory and amplifying role for CA125 in the inflammatory response in HF.