title: Iron deficiency in systemic sclerosis patients with and without pulmonary hypertension.
abstract: OBJECTIVE
  SSc-associated pulmonary hypertension (SSc-PH) has a worse prognosis compared with SSc without PH (SSc-nonPH). Iron deficiency (ID) was previously associated with worse clinical outcome and survival in other types of PH, but ID effects in SSc-PH are unknown. Therefore we investigated the prevalence and clinical significance of ID in systemic sclerosis patients with and without PH.
  
  
  METHODS
  Body iron status was determined in SSc-PH (n = 47) and SSc-nonPH patients (n = 122). ID was defined by circulating soluble transferrin receptor (sTfR) levels >28.1 nmol/l. Clinical and exercise parameters were compared between the groups. Four-year survival after iron measurements was determined.
  
  
  RESULTS
  ID prevalence was 46.1% in SSc-PH compared with 16.4% in SSc-nonPH patients (P < 0.001). Overall hepcidin levels were high compared with reference values and related to sTfR, but not with IL-6 (P = 0.82). Six-minute walking distance and maximal achieved work at ergometry was lower in SSc-PH compared with SSc-nonPH patients (P < 0.001 and P < 0.01, respectively) and was even further reduced in case of ID (P(interaction) < 0.05). In addition, ID SSc-PH patients had a poorer survival compared with non-ID patients [hazard ratio (HR) 0.34, 95% CI 0.14, 0.82, P < 0.05) and a similar trend was observed in SSc-nonPH patients (HR 0.16, 95% CI 0.02, 1.11, P = 0.06).
  
  
  CONCLUSIONS
  ID is more prevalent in SSc-PH than in SSc-nonPH patients and is associated with exercise impairment in both SSc-PH and SSc-nonPH. In addition, ID SSc-PH patients have a significantly worse survival compared with non-ID patients.
authors.affiliation: Department of Pulmonology, Institute for Cardiovascular Research, VU University Medical Center, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands. a.vonk@vumc.nl.
authors.forename: Gerrina
authors.initials: G
authors.lastname: Ruiter
authors.forename: Irene J
authors.initials: IJ
authors.lastname: Lanser
authors.forename: Frances S
authors.initials: FS
authors.lastname: de Man
authors.forename: Willem J
authors.initials: WJ
authors.lastname: van der Laarse
authors.forename: John
authors.initials: J
authors.lastname: Wharton
authors.forename: Martin R
authors.initials: MR
authors.lastname: Wilkins
authors.forename: Luke S
authors.initials: LS
authors.lastname: Howard
authors.forename: Anton
authors.initials: A
authors.lastname: Vonk-Noordegraaf
authors.forename: Alexandre E
authors.initials: AE
authors.lastname: Voskuyl
mesh_terms: D000328:Adult; D000368:Aged; D018798:Anemia, Iron-Deficiency / Q000453:epidemiology* / Q000401:mortality / Q000503:physiopathology; D015897:Comorbidity; D015444:Exercise / Q000502:physiology; D005260:Female; D064451:Hepcidins / Q000097:blood; D006801:Humans; D006976:Hypertension, Pulmonary / Q000453:epidemiology* / Q000401:mortality / Q000503:physiopathology; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015995:Prevalence; D011990:Receptors, Transferrin / Q000097:blood; D012044:Regression Analysis; D012595:Scleroderma, Systemic / Q000453:epidemiology* / Q000401:mortality / Q000503:physiopathology; D015996:Survival Rate
chemical_list: D064451:Hepcidins; D011990:Receptors, Transferrin
keywords: exercise capacity; hepcidin; iron metabolism