Prognostic impact of hypochromic erythrocytes in patients with pulmonary arterial hypertension

Abstract

Background Iron deficiency affects up to 50% of patients with pulmonary arterial hypertension (PAH) but iron markers such as ferritin and serum iron are confounded by several non-disease related factors like acute inflammation and diet. The aim of this study was to identify a new marker for iron deficiency and clinical outcome in PAH patients. Methods In this single-center, retrospective study we assessed indicators of iron status and clinical parameters specifying the time to clinical worsening (TTCW) and survival in PAH patients at time of initial diagnosis and at 1-year follow-up using univariable and multivariable analysis. Results In total, 150 patients were included with an invasively confirmed PAH and complete data on iron metabolism. The proportion of hypochromic erythrocytes > 2% at initial diagnosis was identified as an independent predictor for a shorter TTCW (p = 0.0001) and worse survival (p = 0.002) at initial diagnosis as well as worse survival (p = 0.016) at 1-year follow-up. Only a subset of these patients (64%) suffered from iron deficiency. Low ferritin or low serum iron neither correlated with TTCW nor survival. Severe hemoglobin deficiency at baseline was significantly associated with a shorter TTCW (p = 0.001). Conclusions The presence of hypochromic erythrocytes > 2% was a strong and independent predictor of mortality and shorter TTCW in this cohort of PAH patients. Thus, it can serve as a valuable indicator of iron homeostasis and prognosis even in patients without iron deficiency or anemia. Further studies are needed to confirm the results and to investigate therapeutic implications.

Low-frequency ultrasound for pulmonary hypertension therapy

“…Chronic heart failure develops because of cardiac energy depletion due to oxygen deprivation at the mitochondrial level of cardiomyocytes. Almost 50% of patients with PH develop iron deficiency [ 24 ]. Iron deficiency, due to chronic blood loss or inadequate dietary iron absorption, causes iron deficiency anaemia, while inflammation-induced iron retention in innate immune cells and iron uptake blockade cause anaemia of chronic disease.…”

Hypochromic red cells as a prognostic indicator of survival among patients with systemic sclerosis screened for pulmonary hypertension

“…8 Department of Rheumatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland. 9 Laboratory for Molecular Genetic Diagnostics, Institute of Human Genetics, Heidelberg University, Heidelberg, Germany.…”

“…It was successfully used for the observation of functional ID in rheumatoid arthritis [7] and for monitoring of therapeutic response to iron supplementation in advanced chronic kidney disease [8]. Furthermore, previous data indicate that HRC > 2% could be relevant for the prognosis of patients with pulmonary arterial hypertension (PAH) [9].…”

No genetic causal association between iron status and pulmonary artery hypertension: Insights from a two‐sample Mendelian randomization

“…Iron availability influences pulmonary hemodynamics, modifying basal pulmonary artery pressure and the pulmonary vasoconstrictor response to hypoxia in humans. 2 , 3 Iron deficiency may affect up to 50% of patients with PAH. 4 , 5 Additionally, iron deficiency in PAH patients correlates with more severe disease manifestations, including reduced exercise capacity and poorer survival rates.…”

“…In recent years, the role of iron status in PAH has garnered considerable attention. Iron availability influences pulmonary hemodynamics, modifying basal pulmonary artery pressure and the pulmonary vasoconstrictor response to hypoxia in humans 2,3 . Iron deficiency may affect up to 50% of patients with PAH 4,5 .…”