Clinical Rheumatology

, Volume 38, Issue 4, pp 1117–1124 | Cite as

Pulmonary hypertension in Spanish patients with systemic sclerosis. Data from the RESCLE registry

  • Francisco J. García-HernándezEmail author
  • María J. Castillo-Palma
  • Carles Tolosa-Vilella
  • Alfredo Guillén-del Castillo
  • Manuel Rubio-Rivas
  • Mayka Freire
  • José A. Vargas-Hitos
  • José A. Todolí-Parra
  • Mónica Rodríguez-Carballeira
  • Gerard Espinosa-Garriga
  • Dolores Colunga-Argüelles
  • Norberto Ortego-Centeno
  • Luis Trapiella-Martínez
  • María M. Rodero-Roldán
  • Xavier Pla-Salas
  • Isabel Perales-Fraile
  • Isaac Pons-Martín del Campo
  • Antonio J. Chamorro
  • Rafael A. Fernández-de la Puebla Giménez
  • Ana B. Madroñero-Vuelta
  • Manuel Ruíz-Muñoz
  • Vicent Fonollosa-Pla
  • Carmen P. Simeón-Aznar
  • on behalf of the Spanish Scleroderma Study Group (SSSG)
  • Autoimmune Diseases Study Group (GEAS)
  • Spanish Society of Internal Medicine (SEMI)
Original Article



Our objective was to evaluate the pulmonary hypertension (PH) data for Spanish patients with systemic sclerosis (SSc), define the PH types and determine the associated factors.


Descriptive study of PH-related data from the multicentre RESCLE registry. Estimated systolic pulmonary artery pressure (esPAP), measured via echocardiogram was considered elevated if ≥ 35 mmHg. Left heart disease (LHD) and interstitial lung disease (ILD) were identified. When performed, data from right heart catheterisation (RHC) were collected.


esPAP was elevated in 350 of 808 patients (43.3%). One hundred and forty-four patients (17.8%) were considered to have PH (88 via RHC and the rest due to elevated esPAP along with evidence of significant LHD or ILD): PAH 3.7%, secondary to ILD 8.3%, secondary to LHD 2.8% and unclassified 3%. Prevalence of elevated esPAP was greater in diffuse SSc (dSSc) than in limited scleroderma (lSSc) (50.5 vs. 42.2%, p 0.046). In the group with elevated esPAP, a lower prevalence of anti-centromere antibodies (41.9% vs. 52.3%, p 0.006) and a greater prevalence of anti-topoisomerase-1 antibodies (ATA) (25.1% vs. 18.6%, p 0.04) were observed compared to the group with normal esPAP. Patients with elevated esPAP had a lower rate of digital ulcers (50.6% vs. 60.2%, p 0.007) and esophageal involvement (83.6% vs. 88.7%, p 0.07) and higher rate of renal crisis (4.6% vs. 1.8%, p 0.066).


Prevalence of PAH was lower than expected (3.7%). Probability of having elevated esPAP was higher among patients with dSSc and among those with ATA.


Anti-centromere antibodies Pulmonary hypertension Systemic sclerosis 



We gratefully acknowledge all investigators who form part of the RESCLE registry. This project was possible thanks to an educational unrestricted scholarship granted by Laboratorios Actelion. We also thank the RESCLE Registry Coordinating Center, S&H Medical Science Service, for their quality control data, logistic and administrative support, and Prof. Salvador Ortiz, Universidad Autónoma de Madrid and Statistical Advisor S&H Medical Science Service, for the statistical analysis of the data presented in this paper.

RESCLE Registry members: Argibay A, Boldova R, Callejas Moraga E, Carbonell C, Castillo MJ, Chamorro AJ, Colunga D, Espinosa G, Estévez M, Fernández de la Puebla RA, Fonollosa V, Freire M, García Hernández F, Guillén del Castillo A, Iniesta N, Madroñero AB, Ortego-Centeno N, Perales I, Pestaña M, Pla Salas X, Pons Martín del Campo I, Rodero Roldán MM, Rodríguez Carballeira M, Rubio Rivas M, Ruiz Muñoz M, Segovia P, Simeón CP, Tarí EV, Todolí JA, Tolosa C, Trapiella L, Vargas Hitos JA, Villalba N

Compliance with ethical standards




  1. 1.
    Galiè N, Humbert M, Vachiery JL, Gibbs S, Lang I, Torbicki A, Simonneau G, Peacock A, Vonk Noordegraaf A, Beghetti M, Ghofrani A, Gomez Sanchez MA, Hansmann G, Klepetko W, Lancellotti P, Matucci M, McDonagh T, Pierard LA, Trindade PT, Zompatori M, Hoeper M (2015) 2015 ESC/ERS guidelines for the diagnosis and treatment of pulmonary hypertension: the Joint Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS). Eur Respir J 46:903–975CrossRefGoogle Scholar
  2. 2.
    Kawut SM, Taichman DB, Archer-Chicko CL, Palevsky HI, Kimmel SE (2003) Hemodynamics and survival in patients with pulmonary arterial hypertension related to systemic sclerosis. Chest 123:344–350CrossRefGoogle Scholar
  3. 3.
    McLaughlin VV, Presberg KW, Doyle RL, Abman SH, McCrory DC, Fortin T, Ahearn G, American College of Chest Physicians (2004) Prognosis of pulmonary arterial hypertension: ACCP evidence-based clinical practice guidelines. Chest 126(1 Suppl):78S–92SCrossRefGoogle Scholar
  4. 4.
    Escribano-Subias P, Blanco I, López-Meseguer M, Lopez-Guarch CJ, Roman A, Morales P, Castillo-Palma MJ, Segovia J, Gómez-Sanchez MA, Barberà JA, REHAP investigators (2012) Survival in pulmonary hypertension in Spain: insights from the Spanish registry. Eur Respir J 40:596–603CrossRefGoogle Scholar
  5. 5.
    Sánchez Román J, Opitz C, Kowal-Bielecka O, García Hernández FJ, Castillo Palma MJ, Pittrow D (2008) Screening for PAH in patients with systemic sclerosis: focus on Doppler echocardiography. Rheumatology 47(Suppl 5):V33–V35CrossRefGoogle Scholar
  6. 6.
    García Hernández FJ, Castillo Palma MJ, Montero Mateos E, González León R, López Haldón JE, Sánchez Román J (2016) Screening of pulmonary hypertension in a Spanish cohort of patients with systemic sclerosis. Med Clin (Barc) 146:1–7CrossRefGoogle Scholar
  7. 7.
    (1980) Preliminary criteria for the classification of systemic sclerosis (scleroderma). Subcommittee for scleroderma criteria of the American Rheumatism Association Diagnostic and Therapeutic Criteria Committee. Arthritis Rheum 23:581–586Google Scholar
  8. 8.
    LeRoy EC, Black C, Fleischmajer R, Jablonska S, Krieg T, Medsger TA Jr, Rowell N, Wollheim F (1988) Scleroderma (systemic sclerosis): classification, subsets and pathogensis. J Rheumatol 15:202–205Google Scholar
  9. 9.
    Simeón-Aznar CP, Fonollosa-Plá V, Tolosa-Vilella C, Espinosa-Garriga G, Campillo-Grau M, Ramos-Casals M, García-Hernández FJ, Castillo-Palma MJ, Sánchez-Román J, Callejas-Rubio JL, Ortego-Centeno N, Egurbide-Arberas MV, Trapiellla-Martínez L, Caminal-Montero L, Sáez-Comet L, Velilla-Marco J, Camps-García MT, de Ramón-Garrido E, Esteban-Marcos EM, Pallarés-Ferreres L, Navarrete-Navarrete N, Vargas-Hitos JA, Gómez de la Torre R, Salvador-Cervello G, Rios-Blanco JJ, Vilardell-Tarrés M, Spanish Scleroderma Study Group (SSSG), Autoimmune Diseases Study Group (GEAS), Spanish Society of Internal Medicine (SEMI) (2015) Registry of the Spanish network for systemic sclerosis survival, prognostic factors, and causes of death. Medicine (Baltimore) 94(43):e1728CrossRefGoogle Scholar
  10. 10.
    Steen V (2003) Predictors of end stage lung disease in systemic sclerosis. Ann Rheum Dis 62:97–99CrossRefGoogle Scholar
  11. 11.
    Steen VD, Medsger TA (2007) Changes in causes of death in systemic sclerosis, 1972-2002. Ann Rheum Dis 66:940–944CrossRefGoogle Scholar
  12. 12.
    Hachulla E, Carpentier P, Gressin V, Diot E, Allanore Y, Sibilia J, Launay D, Mouthon L, Jego P, Cabane J, de Groote P, Chabrol A, Lazareth I, Guillevin L, Clerson P, Humbert M, ItinérAIR-Sclérodermie Study Investigators (2009) Risk factors for death and the 3-year survival of patients with systemic sclerosis: the French ItinérAIR-Sclérodermie study. Rheumatology (Oxford) 48:304–308CrossRefGoogle Scholar
  13. 13.
    Tyndall AJ, Bannert B, Vonk M, Airò P, Cozzi F, Carreira PE et al (2010) Causes and risk factors for death in systemic sclerosis: a study from the EULAR Scleroderma Trials and Research (EUSTAR) database. Ann Rheum Dis 69:1809–1815CrossRefGoogle Scholar
  14. 14.
    Hao Y, Hudson M, Baron M, Carreira P, Stevens W, Rabusa C, Tatibouet S, Carmona L, Joven BE, Huq M, Proudman S, Nikpour M, the Canadian Scleroderma Research Group, the Australian Scleroderma Interest Group (2017) Early mortality in a multinational systemic sclerosis inception cohort. Arthritis Rheumatol 69:1067–1077CrossRefGoogle Scholar
  15. 15.
    Elhai M, Meune C, Avouac J, Kahan A, Allanore Y (2012) Trends in mortality in patients with systemic sclerosis over 40 years: a systematic review and meta-analysis of cohort studies. Rheumatology (Oxford) 51:1017–1026CrossRefGoogle Scholar
  16. 16.
    Pope JE, Lee P, Baron M, Dunne J, Smith D, Docherty PS, Bookman A, Abu-Hakima M (2005) Prevalence of elevated pulmonary arterial pressures measured by echocardiography in a multicenter study of patients with systemic sclerosis. J Rheumatol 32:1273–1278Google Scholar
  17. 17.
    Wigley FM, Lima JA, Mayes M, McLain D, Chapin JL, Ward-Able C (2005) The prevalence of undiagnosed pulmonary arterial hypertension in subjects with connective tissue disease at the secondary health card level of community-based rheumatologists (the UNCOVER study). Arthritis Rheum 52:2125–2132CrossRefGoogle Scholar
  18. 18.
    MacGregor AJ, Canavan R, Knight C, Denton CP, Davar J, Coghlan J, Black CM (2001) Pulmonary hypertension in systemic sclerosis: risk factors for progression and consequences for survival. Rheumatology (Oxford) 40:453–459CrossRefGoogle Scholar
  19. 19.
    Mukerjee D, St George D, Coleiro B, Knight C, Denton CP, Davar J, Black CM, Coghlan JG (2003) Prevalence and outcome in systemic sclerosis associated pulmonary arterial hypertension: application of a registry approach. Ann Rheum Dis 62:1088–1093CrossRefGoogle Scholar
  20. 20.
    Vonk MC, Broers B, Heijdra YF, Ton E, Snijder R, van Dijk AP et al (2009) Systemic sclerosis and its pulmonary complications in The Netherlands: an epidemiological study. Ann Rheum Dis 68:961–965CrossRefGoogle Scholar
  21. 21.
    Avouac J, Airò P, Meune C, Beretta L, Dieude P, Caramaschi P et al (2010) Prevalence of pulmonary hypertension in systemic sclerosis in European Caucasians and metaanalysis of 5 studies. J Rheumatol 37:2290–2298CrossRefGoogle Scholar
  22. 22.
    Iudici M, Codullo V, Giuggioli D, Riccieri V, Cuomo G, Breda S et al (2013) Pulmonary hypertension in systemic sclerosis: prevalence, incidence and predictive factors in a large multicentric Italian cohort. Clin Exp Rheumatol 31(2 Suppl 76):31–36Google Scholar
  23. 23.
    Coghlan JG, Denton CP, Grünig E, Bonderman D, Distler O, Khanna D, Müller-Ladner U, Pope JE, Vonk MC, Doelberg M, Chadha-Boreham H, Heinzl H, Rosenberg DM, McLaughlin VV, Seibold JR, on behalf of the DETECT study group (2014) Evidence-based detection of pulmonary arterial hypertension in systemic sclerosis: the DETECT study. Ann Rheum Dis 73:1340–1349CrossRefGoogle Scholar
  24. 24.
    Morrisroe K, Stevens W, Sahhar J, Rabusa C, Nikpour M, Proudman S, Australian Scleroderma Interest Group (ASIG) (2017) Epidemiology and disease characteristics of systemic sclerosis-related pulmonary arterial hypertension: results from a real-life screening programme. Arthritis Res Ther 19:42. CrossRefGoogle Scholar
  25. 25.
    Hsu VM, Chung L, Hummers LK, Wigley F, Simms R, Bolster M, Silver R, Fischer A, Hinchcliff ME, Varga J, Goldberg AZ, Derk CT, Schiopu E, Khanna D, Shapiro LS, Domsic RT, Medsger T, Mayes MD, Furst D, Csuka ME, Molitor JA, Alkassab F, Steen VD (2014) Development of pulmonary hypertension in a high-risk population with systemic sclerosis in the Pulmonary Hypertension Assessment and Recognition of Outcomes in Scleroderma (PHAROS) cohort study. Semin Arthritis Rheum 44:55–62CrossRefGoogle Scholar
  26. 26.
    Simonneau G, Galiè N, Jansa P, Meyer GM, Al-Hiti H, Kusic-Pajic A, Lemarié JC, Hoeper MM, Rubin LJ (2014) Long-term results from the EARLY study of bosentan in WHO functional class II pulmonary arterial hypertension patients. Int J Cardiol 172:332–339CrossRefGoogle Scholar
  27. 27.
    Humbert M, Yaici A, de Groote P, Montani D, Sitbon O, Launay D, Gressin V, Guillevin L, Clerson P, Simonneau G, Hachulla E (2011) Screening for pulmonary arterial hypertension in patients with systemic sclerosis: clinical characteristics at diagnosis and long-term survival. Arthritis Rheum 63:3522–3530CrossRefGoogle Scholar
  28. 28.
    Denton CP, Khanna D (2017) Systemic sclerosis. Lancet 390:1685–1689CrossRefGoogle Scholar
  29. 29.
    Le Pavec J, Humbert M, Mouthon L, Hassoun PM (2010) Systemic sclerosis-associated pulmonary arterial hypertension. Am J Respir Crit Care Med 181:1285–1293CrossRefGoogle Scholar
  30. 30.
    Steen VD (2005) Autoantibodies in systemic sclerosis. Semin Arthritis Rheum 35:35–42CrossRefGoogle Scholar
  31. 31.
    Denton CP, Hachulla E (2011) Risk factors associated with pulmonary arterial hypertension in patients with systemic sclerosis and implications for screening. Eur Respir Rev 20:270–276CrossRefGoogle Scholar
  32. 32.
    Hesselstrand R, Ekman R, Eskilsson J, Isaksson A, Scheja A, Ohlin AK, Akesson A (2005) Screening for pulmonary hypertension in systemic sclerosis: the longitudinal development of tricuspid gradient in 227 consecutive patients, 1992-2001. Rheumatology 44:366–371CrossRefGoogle Scholar
  33. 33.
    Hunzelmann N, Genth E, Krieg T, Lehmacher W, Melchers I, Meurer M, Moinzadeh P, Müller-Ladner U, Pfeiffer C, Riemekasten G, Schulze-Lohoff E, Sunderkoetter C, Weber M, Worm M, Klaus P, Rubbert A, Steinbrink K, Grundt B, Hein R, Scharffetter-Kochanek K, Hinrichs R, Walker K, Szeimies RM, Karrer S, Müller A, Seitz C, Schmidt E, Lehmann P, Foeldvári I, Reichenberger F, Gross WL, Kuhn A, Haust M, Reich K, Böhm M, Saar P, Fierlbeck G, Kötter I, Lorenz HM, Blank N, Gräfenstein K, Juche A, Aberer E, Bali G, Fiehn C, Stadler R, Bartels V, Registry of the German Network for Systemic Scleroderma (2008) The registry of the German Network for Systemic Scleroderma: frequency of disease subsets and patterns of organ involvement. Rheumatology 47:1185–1192CrossRefGoogle Scholar
  34. 34.
    Morrisroe K, Huq M, Stevens W, Rabusa C, Proudman SM, Nikpour M, the Australian Scleroderma Interest Group (ASIG) (2016) Risk factors for development of pulmonary arterial hypertension in Australian systemic sclerosis patients: results from a large multicenter cohort study. BMC Pulm Med 16:134–141CrossRefGoogle Scholar
  35. 35.
    Badesch DB, Wynne KM, Bonvallet S, Voelkel NF, Ridgway C, Groves BM (1993) Hypothyroidism and primary pulmonary hypertension: an autoimmune pathogenetic link? Ann Intern Med 119:44–46CrossRefGoogle Scholar
  36. 36.
    Curnock AL, Dweik RA, Higgins BH, Saadi HF, Arroliga AC (1999) High prevalence of hypothyroidism in patients with primary pulmonary hypertension. Am J Med Sci 318:289–292CrossRefGoogle Scholar
  37. 37.
    Chu JW, Kao PN, Faul JL, Doyle RL (2002) High prevalence of autoimmune thyroid disease in pulmonary arterial hypertension. Chest 122:1668–1673CrossRefGoogle Scholar
  38. 38.
    Castillo Palma MJ, García Hernández FJ, Montero Benavides P, González León R, Ocaña Medina C, Sánchez Román J (2009) Thyroid dysfunction in patients with pulmonary arterial hypertension. A cohort study of 58 patients. Med Clin (Barc) 132:695–700CrossRefGoogle Scholar
  39. 39.
    Castillo-Palma MJ, García-Hernández FJ, Sánchez-Román J (2010) Epoprostenol and thyroid disease. Endocr Pract 16:133Google Scholar

Copyright information

© International League of Associations for Rheumatology (ILAR) 2018

Authors and Affiliations

  • Francisco J. García-Hernández
    • 1
    Email author
  • María J. Castillo-Palma
    • 1
  • Carles Tolosa-Vilella
    • 2
  • Alfredo Guillén-del Castillo
    • 3
  • Manuel Rubio-Rivas
    • 4
  • Mayka Freire
    • 5
  • José A. Vargas-Hitos
    • 6
  • José A. Todolí-Parra
    • 7
  • Mónica Rodríguez-Carballeira
    • 8
  • Gerard Espinosa-Garriga
    • 9
  • Dolores Colunga-Argüelles
    • 10
  • Norberto Ortego-Centeno
    • 11
  • Luis Trapiella-Martínez
    • 12
  • María M. Rodero-Roldán
    • 13
  • Xavier Pla-Salas
    • 14
  • Isabel Perales-Fraile
    • 15
  • Isaac Pons-Martín del Campo
    • 16
  • Antonio J. Chamorro
    • 17
  • Rafael A. Fernández-de la Puebla Giménez
    • 18
  • Ana B. Madroñero-Vuelta
    • 19
  • Manuel Ruíz-Muñoz
    • 20
  • Vicent Fonollosa-Pla
    • 3
  • Carmen P. Simeón-Aznar
    • 3
  • on behalf of the Spanish Scleroderma Study Group (SSSG)
  • Autoimmune Diseases Study Group (GEAS)
  • Spanish Society of Internal Medicine (SEMI)
  1. 1.Department of Internal MedicineHospital Universitario Virgen del RocíoSevilleSpain
  2. 2.Department of Internal MedicineCorporación Sanitaria Universitaria Parc TaulíSabadellSpain
  3. 3.Autoimmune Diseases Unit, Department of Internal MedicineHospital Universitario Vall d’HebronBarcelonaSpain
  4. 4.Department of Internal MedicineHospital Universitario de BellvitgeL’Hospitalet de LlobregatSpain
  5. 5.Systemic Autoimmune Diseases and Thrombosis Unit, Department of Internal MedicineComplejo Hospitalario Universitario de VigoPontevedraSpain
  6. 6.Department of Internal MedicineHospital Universitario Virgen de las NievesGranadaSpain
  7. 7.Department of Internal MedicineHospital Universitario y Politécnico La FeValenciaSpain
  8. 8.Department of Internal MedicineHospital Universitario Mútua TerrassaBarcelonaSpain
  9. 9.Systemic Autoimmune Diseases Unit, Instituto Clínic de Medicina y DermatologíaHospital Universitario ClínicBarcelonaSpain
  10. 10.Department of Internal MedicineHospital Universitario Central de AsturiasOviedoSpain
  11. 11.Systemic Autoimmune Diseases Unit, Department of Internal MedicineHospital Campus de la Salud, Complejo Universitario de GranadaGranadaSpain
  12. 12.Systemic Autoimmune Diseases Unit, Department of Internal MedicineHospital de CabueñesGijónSpain
  13. 13.Autoimmune Diseases Unit, Department of Internal MedicineHospital Clínico Universitario Lozano BlesaZaragozaSpain
  14. 14.Systemic Autoimmune Diseases Unit, Department of Internal MedicineConsorci Hospitalari de VicBarcelonaSpain
  15. 15.Department of Internal MedicineHospital Universitario Rey Juan CarlosMóstolesSpain
  16. 16.Autoimmune Diseases Unit, Department of Internal MedicineHospital de IgualadaBarcelonaSpain
  17. 17.Department of Internal MedicineComplejo Asistencial Universitario de SalamancaSalamancaSpain
  18. 18.Department of Internal MedicineHospital Universitario Reina SofíaCórdobaSpain
  19. 19.Department of Internal MedicineHospital General San JorgeHuescaSpain
  20. 20.Department of Internal MedicineHospital Universitario Fundación AlcorcónMadridSpain

Personalised recommendations