Serum Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand and the Cardiovascular Disease Continuum: Insights from Hypertensive Urgencies and Acute Heart Failure Events

Background: Although TRAIL is a potent propapoptotic factor, its role in cardiovascular disease (CVD) remains unclear. This pilot exploratory study investigated serum TRAIL changes along the CVD continuum. We focused on two successive phases of this spectrum (systemic arterial hypertension and heart failure), with emphasis on acute cardiac events due to their immediate clinical significance. Methods: The study population included 90 age- and sex-matched patients hospitalized with hypertensive urgencies (HTUs) or acute decompensation episodes (ADHF). Key echocardiographic, endothelial, cardiometabolic, renal, and liver markers were assessed alongside TRAIL levels. Results: ADHF patients showed significantly elevated TRAIL concentrations, suggesting a progressive rise in TRAIL levels along the CVD continuum. They exhibited worse cardiac, hematologic, and renal profiles, with longer hospital stays and the cachexic phenotype. TRAIL correlated directly with asymmetric dimethylarginine, C-reactive protein, and admission potassium in ADHF patients. In hypertensive subjects, it correlated directly with asymmetric dimethylarginine and inversely with erythrocyte size variability. TRAIL may, thus, serve as a compensatory mechanism in HF, with potential as a biomarker for acute cardiovascular events. Conclusions: TRAIL dynamics provide valuable insights into CVD pathophysiology, particularly in acute settings, warranting further investigation to clarify its role in the broader context of apoptosis and cardiovascular health.