Aim: Idiopathic myelofibrosis (IMF) is associated with an increased risk of pulmonary arterial hypertension (PAH). We investigated the prevalence of PAH in a large cohort of IMF patients and its possible association with some mechanisms known to be involved in PAH generation.

Materials and methods: Systolic pulmonary arterial pressure (sPAP) was evaluated by transthoracic doppler echocardiography in 37 IMF patients (20 males and 17 females; median age 65.1 years, range 37–83). The patients with sPAP ≥35 mmHg were further evaluated by high-resolution lung CT, lung perfusion scintigraphy, arterial blood gas analysis and pulmonary function tests (PFT), including lung carbon monoxide diffusing capacity. The patients’ circulating endothelial cells (CECs: CD45, CD146+, CD31+) and endothelial progenitor cells (EPCs: CD45, CD133+, CD34+) were evaluated using 4-parameter 3-colour flow cytometry and compared with those of 11 age-matched healthy controls. Serum VEGF, ET-1, TGFβ, PDGF-AB and sE-selectin levels were also determined.

Results: PAH (sPAP ≥35 mmHg) was documented in 13 patients (35%), six of whom (16% of the whole series) had mild PAH (sPAP ≥45 mmHg); three of the patients with PAH were symptomatic. No case of pulmonary hypertension was due to cardiac or lung disease, or thromboembolic events. Median EPC levels were higher in the IMF patients than controls (0.78/μL [range 0–4.3] vs 0.32/μL [range 0.11–0.65]; p=0.003), and lower in the IMF patients with PAH than in those with sPAP <35 mmHg (0.44/μL [range 0–2.73] vs 0.94/μL [range 0.13–4.3]; p=0.02). Additionally, EPC levels in the patients with PAH inversely correlated with SPAP (p=0.02). There were no significant differences in cytokine (ET1, PDGF-AB, TGFβ, sE-selectin) or CEC levels between the IMF patients and controls, or between the IMF patients with or without PAH. Median VEGF levels were higher in the IMF patients than in controls (1449 pg/L [range 266.9–2369.4] vs 281.2 pg/L [range 68.8–1151.7]; p=0.008) and higher in the patients with PAH than in those without (1782.8 pg/L [range 406.8–2306] vs 1037.6 pg/L [range 266.9–2369.4]; p<0.05).

Conclusion: This study shows that PAH is frequent in IMF patients without any known pulmonary or heart complications, being moderate in a subset in whom close follow-up is advisable. IMF and PAH have abnormal angiogenesis in common, and the patients with IMF complicated by PAH had markedly high VEGF levels together with relatively low EPC levels. Our findings suggest that PAH in this setting is associated with abnormalities in angiogenic status rather than the direct endothelial damage expressed by the increased CEC shedding found in other diseases associated with PAH. These results support the hypothesis that common mechanism(s) may be involved in the pathogenesis of IMF and PAH, thus warranting studies of CEP clonality.

Disclosure: No relevant conflicts of interest to declare.

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