Hypoalbuminemia and Mortality in Acute Heart Failure: Mediating Role of Systemic Inflammation and Congestion

AIMS Hypoalbuminemia (HA) is increasingly recognized as a strong predictor of all–cause mortality in patients with acute heart failure (AHF). Because serum albumin correlates with other prognostic factors (e.g., congestion and inflammation), we investigated whether these pathways mediate the association between HA and outcomes. Methods In this retrospective cohort study of patients admitted for AHF, HA was defined as serum albumin ≤3.5 g/dL. We assessed length of hospital stay and 180–day post–discharge mortality. An inflammation score (0–2) was computed from high–sensitivity C–reactive protein and neutrophil–to–lymphocyte ratio (1 point for each biomarker above the median value). A congestion score (0–2) was computed from B–type natriuretic peptide and peripheral hydration assessed by bioimpedance (1 point for each biomarker above the median value). Results Among 400 patients (79±10 years; 51% male), HA was present in 210 (52%) and was associated with more severe presentation and longer hospital stay. In 32% of patients, HA co–occurred with an elevated inflammation score. In–hospital mortality and 180–day mortality was higher in patients with HA than in those without HA (12% vs 3.6% and 47% vs 27%, respectively). At 180 days, HA was associated with mortality (hazard ratio [HR] 2.2, 95% CI 1.5–3.1; P‹0.0001). In multivariable Cox models, HA remained an independent predictor of mortality (HR 1.6, 95% CI 1.1–2.3; P=0.01) along with inflammation and congestion. Mediation analysis showed that inflammation mediated 15% and congestion 16% of the HA–mortality association (31% combined). Conclusions Hypoalbuminemia is common in AHF and is associated with longer hospitalization and higher in–hospital and 180–day mortality. Its prognostic impact is independent of, but partly explained by, systemic inflammation and congestion. These findings may help define a hypoalbuminemic phenotype that could benefit from nutritional support and/or albumin supplementation.