Circulating Pin1 Levels in Patients With Chronic Thromboembolic Pulmonary Hypertension: A Case‐Control Study

Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare but severe complication of pulmonary embolism (PE), yet its underlying mechanisms remain poorly understood. Peptidyl-prolyl cis/trans isomerase (Pin1), a regulatory enzyme involved in thrombosis, inflammation, and vascular remodeling, may contribute to pulmonary vascular disease. We investigated whether circulating Pin1 levels are associated with the risk of CTEPH and its severity. In this case-control study, we measured circulating Pin1 levels by ELISA and compared them across 329 patients with CTEPH, 350 patients after acute PE, and 350 healthy individuals. Associations between Pin1 levels and clinical parameters were assessed with multivariable regression, stratified by sex. Overall, circulating Pin1 levels did not differ between patients with CTEPH, patients after acute PE, and healthy individuals. However, male patients with CTEPH had higher Pin1 levels than the two control groups, while female patients with CTEPH had slightly lower levels than female healthy individuals. Elevated Pin1 levels were associated with improved hemodynamics and exercise capacity, lower N-terminal prohormone of brain natriuretic peptide, and increased probability of CTEPH in men. Among healthy individuals, circulating Pin1 levels varied based on age, sex, and history of cancer. In conclusion, circulating Pin1 did not distinguish between patients with CTEPH, acute PE or healthy individuals. Nonetheless, our results suggest a possible sex-specific association between circulating Pin1 levels and CTEPH. Although Pin1 is unlikely to serve as a standalone biomarker, it may reflect underlying sex-specific pathological mechanisms, and further investigation on its utility within multimodal strategies for early risk stratification of CTEPH is warranted.