Interplay between cholestasis and venous congestion: prognostic impact of alkaline phosphatase and CA125 in acute heart failure

Background

Congestive hepatopathy is characterized by structural heart disease leading to impaired right ventricular function, accompanied by clinical and biochemical signs of systemic venous congestion and cholestasis, after exclusion of alternative causes of liver injury. The present study aimed to evaluate the prognostic impact of the interplay between biochemical cholestasis, assessed by alkaline phosphatase (AP), and systemic venous congestion, reflected by CA125 levels, in patients hospitalized for acute heart failure (AHF).

Methods

We conducted a retrospective observational study using data from the UICA Registry, including 1.305 patients hospitalized for AHF and followed for at least one year. Venous blood samples obtained at admission were used to measure CA125 and cholestatic biomarkers. Patients were classified according to serum AP and CA125 levels. AP values >141 U/L and CA125 levels >60 U/L were considered elevated. Based on these thresholds, patients were categorized into four mutually exclusive categories: (1) low AP and low CA125; (2) high AP with low CA125; (3) low AP with high CA125; and (4) concurrent elevation of both markers.

The primary outcome was all-cause mortality. Survival analyses were performed using Cox proportional hazards models, adjusting for age, B-type natriuretic peptide, presence of peripheral edema, total bilirubin, gamma-glutamyl transferase, heart rate, hemoglobin, systolic blood pressure, and the interaction between alkaline phosphatase and CA125. The interaction between AF and CA125, modeled categorically, and with restricted cubic splines.

Results

Median age was 87 years (IQR 84–91), 67% were women, and median (IQR) AP and CA125 were 88 (71 – 113) U/ml and 55.8 (26.6– 120.5) U/mL. Table 1 shows the differences between the four categories, highlighting category 4 shows markedly greater congestion, worse hepatic markers, more atrial fibrillation, and longer hospitalization, making it the most clinically severe group.

During a median follow-up of 365 days (120-601), 633 patients (45.5%) died and 465 (33.4%) were re hospitalized for heart failure (HF). In multivariable Cox models, a significant interaction was observed between AP and CA125 for mortality (p for interaction = 0.008). Patients with both elevated AP and CA125 had the highest mortality risk (HR: 2.21, 95% CI: 1.43-3.41; p < 0.001), while AP elevation alone was not associated with increased risk.

Conclusions

In elderly patients with acute heart failure, the prognostic impact of AF is influenced by CA125 levels. High levels of AF were associated with higher risk of death only when coexisted with high CA125. On the contrary, when CA125 was low, high AF lacked prognostic effect.

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