Backgrounds Accurate risk stratification is crucial for guiding therapy in medically treated chronic thromboembolic pulmonary hypertension (CTEPH), where inflammation plays a key pathogenic role. This study aimed to identify and validate prognostic inflammatory biomarkers in medically treated CTEPH, with the goal of refining risk assessment and improving clinical management. Methods This dual-cohort study enrolled 576 medically treated CTEPH patients (discovery: 372; validation: 204) from 2009–2021. Plasma levels of inflammatory biomarkers, including soluble suppression tumorigenicity 2 (sST2), Galectin-3, and a panel of cytokines were measured in all participants. The study endpoint was all-cause mortality. The prognostic significance of inflammatory markers was evaluated using Kaplan-Meier survival analysis, Cox regression models, C-index, net reclassification improvement (NRI), and integrated discrimination improvement (IDI). Results Plasma sST2 and interleukin-6 (IL-6) were identified as predictors of survival, and remained robust predictors of mortality after comprehensive adjustment for clinical covariates in both cohorts. Risk stratification using the sST2/IL-6 panel revealed distinct 5-year survival gradients: high sST2/high IL-6 (34.4%), low sST2/high IL-6 (61.4%), high sST2/low IL-6 (78.3%), and low sST2/low IL-6 (90.5%) in the discovery cohort ( p <0.001), with consistent validation. Furthermore, integrating the sST2/IL-6 panel with existing risk models (COMPERA, COMPERA 2.0, FPHN invasive, FPHN noninvasive, and REVEAL2.0) significantly enhanced their prognostic discriminatory power, as evidenced by increased C-indexes, NRI and IDI in both cohorts. Conclusions sST2 and IL-6 are independent prognostic biomarkers in medically treated CTEPH. Their combined use enhances risk stratification and adds incremental value to existing risk models.
Liu et al. (Thu,) studied this question.