###### Abstract  
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 cache 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. Keywords:TRAIL; cardiovascular disease; TNFSF 10; heart failure; hypertension; acute cardiac events +
Footnote †: journal:specific clinical needs [4]. For example, blood pressure monitoring is routinely used to assess and manage SAH [5]. N-terminal pro b-type natriuretic peptide (NT-proBNP) is employed to monitor cardiac stress and fluid status, important in managing both SAH and HF [6]. Asymmetric dimethylarginine (ADMA) offers insights into endothelial dysfunction throughout the CVD spectrum [7]. The relationship between apoptosis--a regulated form of cell death--and CVD is, however, less explored. Altered apoptosis in SAH causes vascular remodeling [8]. These pathological changes promote arterial stiffness and resistance, thus elevating blood pressure and straining the heart [8]. Specifically, apoptosis has been reported in various hypertension models and is associated with cardiovascular remodeling processes like hypertrophy and hyperplasia [8; 9] As CVD progresses to HF, apoptosis is pivotal for the loss of cardiac myocytes, reducing cardiac output and inducing pathological remodeling and cardiac fibrosis [10; 11]. The tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is known as a major proapoptotic actor in cancer [12]. However, accumulating data provides evidence of its involvement in various non-cancerous diseases, including diabetes and CVD [13]. The interplay between TRAIL and the CVD spectrum involves complex interactions with vascular cells, inflammatory processes, and immune responses. Strong evidence supports the role of this protein in myocardial apoptosis [14]. There is also indication that TRAIL contributes to cardiac hypertrophy by promoting inflammatory pathways and apoptosis [15]. High levels appear to be protective in HF, whether with preserved or reduced ejection fraction [16; 17]. Low TRAIL, by contrast, is linked to increased risks of rehospitalization and mortality in HF patients over up to five years [18]. However, the role of TRAIL in CVD is still not fully understood, and data on TRAIL levels across the CVD spectrum are sparse and vary significantly across different patient studies and conditions [19]. Here, we focus on serum TRAIL concentrations in acute phases; more precisely, we investigate hypertensive urgencies (HTUs) for SAH and episodes of acute decompensation (ADHF) for HF. In these critical conditions, TRAIL measurements can provide immediate and pertinent information on acute inflammatory responses and cellular stress [18].