Reduced gastrointestinal iron uptake in pulmonary arterial hypertension: A prospective cross-sectional study

L. Repsold (Heidelberg)¹, S. Harutyunova (Heidelberg)², E. Grünig (Heidelberg)², N. Benjamin (Heidelberg)², P. Xanthouli (Heidelberg)¹, B. Egenlauf (Heidelberg)¹, A. Florea (Heidelberg)¹, M. Shaukat (Heidelberg)¹, R. Sparla (Heidelberg)³, C. Mertens (Heidelberg)⁴, M. Muckenthaler (Heidelberg)⁵, C. Eichstaedt (Heidelberg)^2
1Thoraxklinik - Heidelberg gGmbH Pneumologie und Beatmungsmedizin / Zentrum für Pulmonale Hypertonie Heidelberg, Deutschland; ²Universitätsklinikum Heidelberg Thoraxklinik Heidelberg, Deutschland; ³Universitätsklinikum Heidelberg Otto-Meyerhof-Zentrum - Medizinische Klinik III Heidelberg, Deutschland; ⁴Universitätsklinik Heidelberg Department of Pediatric Oncology, Hematology, Immunology and Pulmonology, Molecular Medicine Partnership Unit (MMPU) Heidelberg, Deutschland; ⁵EMBL und Universität Heidelberg Department of Pediatric Oncology, Hematology, Immunology and Pulmonology, Molecular Medicine Partnership Unit (MMPU) Heidelberg, Deutschland

Background: Iron deficiency (ID) is common in patients with pulmonary arterial hypertension (PAH) and is associated with worse clinical outcomes. The etiology of ID in PAH is poorly understood. The aim of this study was to systematically determine whether differences in oral iron absorption exist between PAH patients with and without chronic ID compared with healthy controls.

Methods: This single-center prospective, cross-sectional cohort study enrolled 45 subjects: 15 PAH patients with chronic ID, 15 PAH patients without ID and 15 healthy age and sex matched controls. Chronic ID was defined by either recorded ID anemia or clinical indication for i.v. iron supplementation in the past 3 years. Plasma iron levels and transferrin saturation (TSAT) were measured before and after a standardized oral iron absorption test with 200 mg ferrous iron. Additional iron and inflammation laboratory parameters were determined. Hepcidin and erythroferrone levels were measured using enzyme-linked immunosorbent assay, and tumor necrosis factor alpha and ferroportin expression were determined by quantitative polymerase chain reaction.

Results: Both PAH groups showed a similar increase of plasma iron and TSAT after 3 h. The increase in plasma iron and TSAT was significantly lower in both PAH groups (with chronic ID: 71.5 (IQR 44.1–188.8) µg/dl; 22 (IQR 14–49) %; without ID: 86.0 (IQR 27.9–105.6) µg/dl; 26 (IQR 11–42) %) compared to healthy controls (154.1 (IQR 129.0–181.5) µg/dl; 45 (IQR 34–54) %, p=0.015 and p=0.031, respectively).

Conclusions: This study is the first to demonstrate a significantly reduced gastrointestinal iron uptake in PAH patients compared to healthy age and sex matched controls. Interestingly, PAH patients with chronic ID showed similar iron uptake levels as those without, suggesting that factors other than iron stores, such as chronic inflammation, may impair iron absorption in this patient population.