Blood based and imaging biomarkers in pulmonary hypertension: An endeavour for new diagnostic tools and insights in disease

Pulmonary hypertension (PH) is a progressive and life‐threatening condition characterized by elevated pulmonary arterial pressure and vascular remodeling, ultimately leading to right heart failure and death. Early diagnosis is essential, as treatment initiated in the early stages improves prognosis and quality of life. However, clinical recognition is often delayed due to nonspecific symptoms and the need for invasive right heart catheterization to confirm the diagnosis. Identifying reliable noninvasive biomarkers could therefore transform clinical care by enabling earlier detection, risk stratification, and monitoring of disease progression. This thesis explores circulating and microvascular biomarkers in PH, with a focus on their potential diagnostic and pathophysiological significance. The work comprises a systematic review of circulating biomarkers in various PH subtypes—pulmonary arterial hypertension (PAH), chronic thromboembolic PH (CTEPH), PH due to left heart disease (PH-LHDm), and pulmonary veno-occlusive disease (PVOD)—and original studies investigating circulating progenitor cells, platelet characteristics, and nailfold microvascular imaging. The systematic review identified multiple promising biomarkers related to inflammation, endothelial dysfunction, and remodeling. Yet, heterogeneity in study design, analytical methods, and patient selection limits direct clinical translation. Subsequent studies demonstrated altered numbers and phenotypes of circulating progenitor cells in PAH and CTEPH, suggesting impaired vascular repair mechanisms. Platelet function analysis revealed enhanced activation patterns, implicating platelets as active contributors to vascular injury rather than passive bystanders. Furthermore, nailfold videocapillaroscopy provided noninvasive visualization of microvascular abnormalities correlating with hemodynamic severity, pointing toward its potential as a bedside biomarker. Collectively, these findings support the concept that PH is a systemic vascular disease involving disturbed cellular cross‐talk between the endothelium, circulating progenitors, and platelets. Combining cellular and microvascular biomarkers may improve early recognition and individualized monitoring of patients at risk for PH. Future research should focus on longitudinal validation and integration of these markers into clinical risk models to optimize early intervention and therapeutic outcomes.