Background: Upregulation of the immune system is regarded to play an important role in the etiopathobiology of pulmonary arterial hypertension (PAH) and inoperable chronic thromboembolic pulmonary hypertension (CTEPH). To the best of our knowledge, neopterin (NP) has never been investigated in patients with PAH and CTEPH. Objectives: The aim of the study was to evaluate the concentration of NP in blood in order to examine its impact on outcome and relationship with disease severity in that population. Methods: Serum concentration of NP was analysed prospectively in 50 patients (36 with PAH and 14 with CTEPH vs. 31 healthy controls) and assessed in relation to clinical parameters and outcome. Results: NP concentration in the PAH and CTEPH groups combined was significantly higher than in the control group (8.68, 6.39-15.03 vs. 5.14, 4.16-5.98 nmol/L, p < 0.0000001). During 9 months of follow-up, clinical deterioration occurred in 18 patients (including 8 deaths), and NP concentration in this group was higher when compared to stable patients (15.6, 8.52-25.13 vs. 7.87, 6.18-9.89, p = 0.002). The cutoff value of NP derived from ROC curve analysis was 15.3 nmol/L (p = 0.002, AUC 0.77, p = 0.0004, HR = 4.35, 95% CI 1.43-13.18, log-rank test). On Cox regression analysis, NP predicted clinical deterioration (p = 0.009, 95% CI 1.01-1.06). NP correlated positively with NT-proBNP (p < 0.001), red blood cell distribution width (p < 0.001), and right atrium area (p = 0.002) and inversely with 6-min walking test (p = 0.002) and peak oxygen consumption (p = 0.001). Conclusions: NP concentration is increased in patients with PAH and inoperable CTEPH. Elevated NP concentration is associated with adverse clinical outcomes and correlates with clinical parameters.
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Smukowska-Gorynia, A., Marcinkowska, J., Chmara, E., Malaczynska-Rajpold, K., Slawek-Szmyt, S., Cieslewicz, A., … Mularek-Kubzdela, T. (2018). Neopterin as a biomarker in patients with pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension. Respiration, 96(3), 222–230. https://doi.org/10.1159/000488908
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