Evaluation of sST2 and sTWEAK levels in patients diagnosed with pulmonary arterial hypertension

Introduction and Objective: Pulmonary arterial hypertension (PAH) is a serious progressive cardiovascular disease that can lead to progressive right heart failure and death if left untreated. In PAH, inflammation, pulmonary vascular vasoconstriction, and pulmonary vascular remodeling play important roles in its pathophysiology. Extensive research has been conducted on biomarkers involved in the pathogenesis of PAH. Soluble tumor necrosis factor-like weak inducer of apoptosis (sTWEAK) is a cytokine belonging to the tumor necrosis factor superfamily and plays a role in apoptosis, inflammation, and cellular immune responses. It has been shown to be effective in modulating inflammatory processes and maintaining vascular integrity. Soluble suppression of tumorigenicity 2 (sST2) is a molecule belonging to the IL-33 receptor family and functions as a soluble receptor that antagonizes the inflammatory effects of IL-33. Both biomarkers have been shown to be associated with cardiovascular diseases and inflammatory processes and have been reported as potential prognostic markers. This study aimed to investigate the role of sTWEAK and sST2 in the pathophysiology of PAH and their potential use in clinical practice. Materials and Methods: This prospective study included 48 PAH patients and 40 healthy individuals who presented to the cardiology clinic. Baseline data of all participants were recorded, and detailed echocardiographic evaluations were performed. For the measurement of sST2 and sTWEAK using commercial kits, blood samples were centrifuged at 5000 rpm for 5 minutes and stored at -80°C. Results: Among the 48 PAH patients included in the study, 32 (66.6%) were female, and 16 (33.3%) were male. The demographic and baseline laboratory parameters of the patient and control groups were similar (p>0.05 for all). However, sST2 (p<0.001) and sTWEAK (p<0.001) levels were significantly higher in individuals with PAH compared to the control group. In the ROC analysis, the best cutoff value for predicting PAH was 9.63 for sST2 (AUC: 0.798, p<0.001), while it was 3.11 for sTWEAK (AUC: 0.797, p<0.001). To assess how sST2 and sTWEAK levels were affected by functional capacity (FC) in PAH patients, the patient group was divided into two classes based on their functional capacity (patients with FC I-II and those with FC III-IV). When comparing these two groups, sST2 levels were found to be significantly higher in FC III-IV patients (p=0.024), whereas no significant difference was detected for sTWEAK (p=0.182). Additionally, PAH patients were classified into three groups according to risk stratification: low, intermediate, and high risk. Accordingly, sST2 levels significantly increased as the risk level increased (p=0.004), whereas no significant difference was found for sTWEAK (p=0.188). Conclusion: In our study, sST2 and sTWEAK levels were found to be significantly higher in PAH patients compared to the control group. Additionally, sST2 provided more significant information for risk assessment in PAH patients compared to sTWEAK. These findings suggest that sST2 and sTWEAK may provide useful information in the diagnosis and prognosis of PAH patients.