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Abstract Number: 0387

Altered Iron Homeostasis and Pulmonary Haemodynamics in Systemic Sclerosis Associated Pulmonary Arterial Hypertension

Alper Sari1, Christopher Denton2, Svetlana Nihtyanova3, Benjamin Schreiber4 and Voon Ong3, 1Hacettepe University, Division of Rheumatology, Department of Internal Medicine, Faculty of Medicine, Ankara, Turkey, 2University College London, London, United Kingdom, 3Centre for Rheumatology, Royal Free Campus, UCL Division of Medicine, UK, London, United Kingdom, 4UCL, London, United Kingdom

Meeting: ACR Convergence 2020

Keywords: Biomarkers, Mortality, pulmonary, Scleroderma, Systemic sclerosis

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Session Information

Date: Friday, November 6, 2020

Session Title: Systemic Sclerosis & Related Disorders – Clinical Poster I

Session Type: Poster Session A

Session Time: 9:00AM-11:00AM

Background/Purpose: Iron deficiency (ID) is more frequent in systemic sclerosis (SSc) patients with pulmonary hypertension (PH) than those without and associated with worse prognosis. There is paucity of data on the relationship between serum iron parameters and pulmonary haemodynamics.

Methods: Right heart catheterisation (RHC) reports of SSc patients were retrospectively reviewed. Subjects were included in the study if they had serum iron studies done within 12 months of RHC and were either diagnosed as 1) pulmonary arteral hypertension (PAH, group 1 PH), defined as mean pulmonary artery pressure (mPAP)≥25 mmHg at rest with pulmonary artery wedge pressure ≤15 mmHg; or 2) no PH.  Patients with gastrointestinal disorders that may cause low iron levels and glomerular filtration rate below 60 ml/min/1.73m2 were excluded. We recorded serum iron concentration (µmol/L), total iron-binding capacity (TIBC, µmol/L), transferrin saturation (TS, %), ferritin (µg/L), red cell distribution width (RDW, %), as well as mPAP (mmHg) and pulmonary vascular resistance (PVR, dynes/sec/cm-5). Univariable assocıatıons were assessed using Mann-Whitney test and Spearman’s correlation as appropriate. Multiple regression of log-transformed mPAP and PVR and Cox regression were used to compare iron and RDW association with haemodynamics and survival.    

Results: We included 122 subjects in the analysis, 84% were female and mean age at RHC was 57 years. The majority (73%) had limited cutaneous SSc and 34% carried anti-centromere antibodies, followed by 18% with anti-Scl70 and 8% with anti-U3RNP.

At RHC, 53/122 (43%) of the patients were diagnosed with PAH. Among them we observed substantially lower levels of serum iron (8.7 vs. 12.1 µmol/L, p< 0.001), TS (15.3% vs. 22.5%, p< 0.001), ferritin (68.1 vs. 112.5 µg/L, p=0.07), significantly higher RDW (16.4% vs. 14.8%, p< 0.001) and no difference in TIBC (57.4 vs. 54.3 µmol/L, p=0.163), compared to subjects in whom PH was excluded.  

mPAP showed moderately strong negative correlation with iron concentration (Spearman’s rho=-0.35, p< 0.001) and TS (Spearman's rho=-0.39, p< 0.001) and positive correlation with RDW (Spearman's rho=0.46, p< 0.001).

PVR was significantly inversely correlated with iron concentration (Spearman’s rho=-0.30, p=0.001), TS (Spearman’s rho=-0.37, p< 0.001 and ferritin (Spearman's rho=-0.22, p=0.016), while it showed positive correlation with TIBC (Spearman's rho=0.28, p=0.003) and RDW (Spearman's rho=0.37, p< 0.001).

Compared to serum iron indices, RDW is a better predictor of mPAP and PVR. In addition, iron levels did not demonstrate any association with survival, while risk of death was significantly higher for patients with higher RDW (HR=1.18, p=0.002) and the association remained after adjusting for presence of PH (HR=1.16, p=0.013).

Conclusion: To our knowledge, this is the first study to demonstrate a significant relationship between ID state and  haemodynamic measures of SSc-PAH. Our data also support RDW, as an indicator for functional iron deficiency, may serve as a biomarker for severity of pulmonary vasculopathy in SSc.


Disclosure: A. Sari, None; C. Denton, Janssen, 1, GlaxoSmithKline, 1, 2, Bayer, 1, Sanofi, 1, Inventiva, 1, 2, Boehringer Ingelheim, 1, Roche, 1, Bristol-Myers Squibb, 1, CSL Behring, 1, 2, UCB, 1, Leadiant Biosciences, 1, Corbus Pharmaceuticals, 1, Acceleron Pharma, 1, Horizon Therapeutics, 1, Forbius, 1, Servier, 1; S. Nihtyanova, GlaxoSmithKline, 3; B. Schreiber, None; V. Ong, None.

To cite this abstract in AMA style:

Sari A, Denton C, Nihtyanova S, Schreiber B, Ong V. Altered Iron Homeostasis and Pulmonary Haemodynamics in Systemic Sclerosis Associated Pulmonary Arterial Hypertension [abstract]. Arthritis Rheumatol. 2020; 72 (suppl 10). https://acrabstracts.org/abstract/altered-iron-homeostasis-and-pulmonary-haemodynamics-in-systemic-sclerosis-associated-pulmonary-arterial-hypertension/. Accessed April 11, 2021.
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