Current Hypertension Reports

, Volume 15, Issue 6, pp 638–649

Epidemiology of Pulmonary Arterial Hypertension

Pulmonary Hypertension (Z-C Jing, Section Editor)

Abstract

The epidemiology of pulmonary arterial hypertension (PAH) has changed over the last decade. Remarkable advances in understanding the pathobiology and clinical care required in PAH have resulted in improved quality of life and survival. Despite such important progress, the long-term rate of survival is still unacceptable. The epidemiology of PAH could not be easily generalized globally, due to the fact that nearly all of the present data has been gathered from Western, multicenter, prospective registries. There are potentially marked differences in PAH patients from Western and Eastern populations, and from developed and developing countries. Therefore, it is clear that more registry data will be needed to address novel questions emerging with improved knowledge of PAH.

Keywords

Pulmonary arterial hypertension PAH Epidemiology Prognosis Heritable PAH Connective tissue disease Congenital heart disease CHD Human immunodeficiency virus HIV Portopulmonary hypertension PoPH Drugs Toxins Schistosomiasis Pulmonary veno-occlusive disease PVOD 

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    Galiè N, Palazzini M, Manes A. Pulmonary arterial hypertension: from the kingdom of the near-dead to multiple clinical trial meta-analyses. Eur Heart J. 2010;31(17):2080–6.PubMedCrossRefGoogle Scholar
  2. 2.
    Rabinovitch M. Molecular pathogenesis of pulmonary arterial hypertension. J Clin Invest. 2012;122(12):4306–13.PubMedCrossRefGoogle Scholar
  3. 3.
    McLaughlin VV, Archer SL, Badesch DB, Barst RJ, Farber HW, Lindner JR, et al. ACCF/AHA expert consensus document on pulmonary hypertension a report of the American College of Cardiology Foundation Task Force on Expert Consensus Documents and the American Heart Association developed in collaboration with the American College of Chest Physicians; American Thoracic Society, Inc.; and the Pulmonary Hypertension Association. J Am Coll Cardiol. 2009;53(17):1573–619.PubMedCrossRefGoogle Scholar
  4. 4.
    • Galiè N, Hoeper MM, Humbert M, Torbicki A, Vachiery JL, Barbera JA, et al. Guidelines for the diagnosis and treatment of pulmonary hypertension: the Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS), endorsed by the International Society of Heart and Lung Transplantation (ISHLT). Eur Heart J. 2009;30(20):2493–537. ESC/ERS/ISHLT guidelines for the diagnosis and treatment of pulmonary hypertension.PubMedCrossRefGoogle Scholar
  5. 5.
    •• Galiè N, Manes A, Negro L, Palazzini M, Bacchi-Reggiani ML, Branzi A. A meta-analysis of randomized controlled trials in pulmonary arterial hypertension. Eur Heart J. 2009;30(4):394–403. The first meta-analysis of randomized controlled trials performed in patients with PAH suggesting an improvement of survival in the patients treated with the targeted therapies approved for PAH.PubMedCrossRefGoogle Scholar
  6. 6.
    •• Rich S, Dantzker DR, Ayres SM, Bergofsky EH, Brundage BH, Detre KM, et al. Primary pulmonary hypertension. A national prospective study. Ann Intern Med. 1987;107(2):216–23. This first prospective and nationwide registry demonstrated the baseline characteristics of primary pulmonary hypertension.PubMedCrossRefGoogle Scholar
  7. 7.
    •• D'Alonzo GE, Barst RJ, Ayres SM, Bergofsky EH, Brundage BH, Detre KM, et al. Survival in patients with primary pulmonary hypertension. Results from a national prospective registry. Ann Intern Med. 1991;115(5):343–9. The prognostic data in the primary NIH pulmonary hypertension cohort revealed a disastrous long-term survival rate when patients only received conventional therapies, with a median survival rate of only 2.8 years after diagnosis.PubMedCrossRefGoogle Scholar
  8. 8.
    •• Humbert M, Sitbon O, Chaouat A, Bertocchi M, Habib G, Gressin V, et al. Pulmonary arterial hypertension in France: results from a national registry. Am J Respir Crit Care Med. 2006;173(9):1023–30. This registry represents the largest population of patients with PAH since the availability of a novel diagnostic classification of the condition and the development of disease-specific therapies, allowing an updated description of this orphan disease in the Western world.PubMedCrossRefGoogle Scholar
  9. 9.
    • Humbert M, Sitbon O, Yaïci A, Montani D, O'Callaghan DS, Jaïs X, et al. French Pulmonary Arterial Hypertension Network. Survival in incident and prevalent cohorts of patients with pulmonary arterial hypertension. Eur Respir J. 2010;36(3):549–55. The first study to reveal a better survival in incident PAH patients compared with those having prevalent PAH.PubMedCrossRefGoogle Scholar
  10. 10.
    • Humbert M, Sitbon O, Chaouat A, Bertocchi M, Habib G, Gressin V, et al. Survival in patients with idiopathic, familial, and anorexigen-associated pulmonary arterial hypertension in the modern management era. Circulation. 2010;122(2):156–63. This study demonstrated that idiopathic, familial, and anorexigen-associated PAH remains a progressive, fatal disease in the modern management era, with a 3-year rate of survival of only 54.9 % in incident cases.PubMedCrossRefGoogle Scholar
  11. 11.
    • Badesch DB, Raskob GE, Elliott CG, Krichman AM, Farber HW, Frost AE, et al. Pulmonary arterial hypertension: baseline characteristics from the REVEAL Registry. Chest. 2010;137(2):376–87. Baseline characteristics that provided important information on WHO group 1 PAH in the largest PAH registry.PubMedCrossRefGoogle Scholar
  12. 12.
    Frost AE, Badesch DB, Barst RJ, Benza RL, Elliott CG, Farber HW, et al. The changing picture of patients with pulmonary arterial hypertension in the United States: how REVEAL differs from historic and non-US Contemporary Registries. Chest. 2011;139(1):128–37.PubMedCrossRefGoogle Scholar
  13. 13.
    Benza RL, Miller DP, Barst RJ, Badesch DB, Frost AE, McGoon MD. An evaluation of long-term survival from time of diagnosis in pulmonary arterial hypertension from the REVEAL Registry. Chest. 2012;142(2):448–56.PubMedCrossRefGoogle Scholar
  14. 14.
    Escribano-Subias P, Blanco I, López-Meseguer M, Lopez-Guarch CJ, Roman A, Morales P, et al. Survival in pulmonary hypertension in Spain: insights from the Spanish registry. Eur Respir J. 2012;40(3):596–603.PubMedCrossRefGoogle Scholar
  15. 15.
    Ling Y, Johnson MK, Kiely DG, Condliffe R, Elliot CA, Gibbs JS, et al. Changing demographics, epidemiology, and survival of incident pulmonary arterial hypertension: results from the pulmonary hypertension registry of the United Kingdom and Ireland. Am J Respir Crit Care Med. 2012;186(8):790–6.PubMedCrossRefGoogle Scholar
  16. 16.
    Hoeper MM, Huscher D, Ghofrani HA, Delcroix M, Distler O, Schweiger C, et al. Elderly patients diagnosed with idiopathic pulmonary arterial hypertension: results from the COMPERA registry. Int J Cardiol. 2012 Nov 16.Google Scholar
  17. 17.
    Dresdale DT, Schultz M, Michtom RJ. Primary pulmonary hypertension. I. Clinical and hemodynamic study. Am J Med. 1951;11(6):686–705.PubMedCrossRefGoogle Scholar
  18. 18.
    Loyd JE, Primm RK, Newman JH. Familial primary pulmonary hypertension: clinical patterns. Am Rev Respir Dis. 1984;129(1):194–7.PubMedGoogle Scholar
  19. 19.
    Loyd JE, Butler MG, Foroud TM, Conneally PM, Phillips 3rd JA, Newman JH. Genetic anticipation and abnormal gender ratio at birth in familial primary pulmonary hypertension. Am J Respir Crit Care Med. 1995;152(1):93–7.PubMedCrossRefGoogle Scholar
  20. 20.
    •• Nichols WC, Koller DL, Slovis B, Foroud T, Terry VH, Arnold ND, et al. Localization of the gene for familial primary pulmonary hypertension to chromosome 2q31-32. Nat Genet. 1997;15(3):277–80. One of the first studies that uncovered the localization of the gene for FPAH.PubMedCrossRefGoogle Scholar
  21. 21.
    •• Morse JH, Jones AC, Barst RJ, Hodge SE, Wilhelmsen KC, Nygaard TG. Mapping of familial primary pulmonary hypertension locus (PPH1) to chromosome 2q31-q32. Circulation. 1997;95(12):2603–6. One of the first studies that uncovered the localization of a gene for FPAH.PubMedCrossRefGoogle Scholar
  22. 22.
    Lane KB, Machado RD, Pauciulo MW, Thomson JR, Phillips III JA, Loyd JE, et al. Heterozygous germline mutations in BMPR2, encoding a TGF-b receptor, cause familial primary pulmonary hypertension. The International PPH Consortium. Nat Genet. 2000;26(1):81–4. The first study that confirmed that BMPR2 mutation could cause familial primary pulmonary hypertension.PubMedCrossRefGoogle Scholar
  23. 23.
    Deng Z, Morse JH, Slager SL, Cuervo N, Moore KJ, Venetos G, et al. Familial primary pulmonary hypertension (gene PPH1) is caused by mutations in the bone morphogenetic protein receptor-II gene. Am J Hum Genet. 2000;67(3):737–44.PubMedCrossRefGoogle Scholar
  24. 24.
    Machado RD, Eickelberg O, Elliott CG, Geraci MW, Hanaoka M, Loyd JE, et al. Genetics and genomics of pulmonary arterial hypertension. J Am Coll Cardiol. 2009;54(1 suppl):S32–42.PubMedCrossRefGoogle Scholar
  25. 25.
    • Sztrymf B, Coulet F, Girerd B, Yaici A, Jais X, Sitbon O, et al. Clinical outcomes of pulmonary arterial hypertension in carriers of BMPR2 mutation. Am J Respir Crit Care Med. 2008;177(12):1377–83. The first study to reveal that the BMPR2 mutation carriers with PAH present approximately 10 years earlier than noncarriers, with a more severe hemodynamic compromise at diagnosis.PubMedCrossRefGoogle Scholar
  26. 26.
    Rosenzweig EB, Morse JH, Knowles JA, Knowles JA, Chada KK, Khan AM, et al. Clinical implications of determining BMPR2 mutation status in a large cohort of children and adults with pulmonary arterial hypertension. J Heart Lung Transplant. 2008;27(6):668–74.PubMedCrossRefGoogle Scholar
  27. 27.
    Aldred MA, Machado RD, James V, Morrell NW, Trembath RC. Characterization of the BMPR2 5’-untranslated region and a novel mutation in pulmonary hypertension. Am J Respir Crit Care Med. 2007;176(8):819–24.PubMedCrossRefGoogle Scholar
  28. 28.
    Cogan JD, Pauciulo MW, Batchman AP, Prince MA, Robbins IM, Hedges LK, et al. High frequency of BMPR2 exonic deletions/duplications in familial pulmonary arterial hypertension. Am J Respir Crit Care Med. 2006;174(5):590–8.PubMedCrossRefGoogle Scholar
  29. 29.
    Machado RD, Aldred MA, James V, Harrison RE, Patel B, Schwalbe EC, et al. Mutations of the TGF-beta type II receptor BMPR2 in pulmonary arterial hypertension. Hum Mutat. 2006;27(2):121–32.PubMedCrossRefGoogle Scholar
  30. 30.
    Girerd B, Montani D, Coulet F, Sztrymf B, Yaici A, Jaïs X, et al. Clinical outcomes of pulmonary arterial hypertension in patients carrying an ACVRL1 (ALK1) mutation. Am J Respir Crit Care Med. 2010;181(8):851–61.PubMedCrossRefGoogle Scholar
  31. 31.
    McAllister KA, Grogg KM, Johnson DW, Gallione CJ, Baldwin MA, Jackson CE, et al. Endoglin, a TGF-beta binding protein of endothelial cells, is the gene for hereditary haemorrhagic telangiectasia type 1. Nat Genet. 1994;8(4):345–51.PubMedCrossRefGoogle Scholar
  32. 32.
    Johnson DW, Berg JN, Baldwin MA, Gallione CJ, Marondel I, Yoon SJ, et al. Mutations in the activin receptorlike kinase 1 gene in hereditary haemorrhagic telangiectasia type 2. Nat Genet. 1996;13(2):189–95.PubMedCrossRefGoogle Scholar
  33. 33.
    Chen YJ, Yang QH, Liu D, Liu QQ, Eyries M, Wen L, et al. Clinical and genetic characteristics of Chinese patients with hereditary haemorrhagic telangiectasia-associated pulmonary hypertension. Eur J Clin Invest. 2013 Jul 10.Google Scholar
  34. 34.
    Shintani M, Yagi H, Nakayama T, Saji T, Matsuoka R. A new nonsense mutation of SMAD8 associated with pulmonary arterial hypertension. J Med Genet. 2009;46(5):331–7.PubMedCrossRefGoogle Scholar
  35. 35.
    Austin ED, Ma L, LeDuc C, Berman Rosenzweig E, Borczuk A, Phillips 3rd JA, et al. Whole exome sequencing to identify a novel gene (caveolin-1) associated with human pulmonary arterial hypertension. Circ Cardiovasc Genet. 2012;5(3):336–43.PubMedCrossRefGoogle Scholar
  36. 36.
    • Ma L, Roman-Campos D, Austin ED, Eyries M, Sampson KS, Soubrier F, et al. A novel channelopathy in pulmonary arterial hypertension. N Engl J Med. 2013;369(4):351–61. The results of this study indicated that in some patients, the KCNK3 mutation might be regarded as a kind of channelopathy.PubMedCrossRefGoogle Scholar
  37. 37.
    Liu D, Wu WH, Mao YM, Yuan P, Zhang R, Ju FL, et al. BMPR2 mutations influence phenotype more obviously in male patients with pulmonary arterial hypertension. Circ Cardiovasc Genet. 2012;5(5):511–8.PubMedCrossRefGoogle Scholar
  38. 38.
    • Condliffe R, Kiely DG, Peacock AJ, Corris PA, Gibbs JS, Vrapi F, et al. Connective tissue disease-associated pulmonary arterial hypertension in the modern treatment era. Am J Respir Crit Care Med. 2009;179(2):151–7. The first prospective, large-scale registry of CTD-PAH in the modern therapeutic era demonstrated that the survival of patients with SSc-PAH in the modern treatment era is better than in the historical series, and that SLE-PAH has a better prognosis than SSc-PAH.PubMedCrossRefGoogle Scholar
  39. 39.
    Chang B, Schachna L, White B, Wigley FM, Wise RA. Natural history of mild- moderate pulmonary hypertension and the risk factors for severe pulmonary hypertension in scleroderma. J Rheumatol. 2006;33(2):269–74.PubMedGoogle Scholar
  40. 40.
    Cox SR, Walker JG, Coleman M, Rischmueller M, Proudman S, Smith MD, et al. Isolated pulmonary hypertension in scleroderma. Intern Med J. 2005;35(1):28–33.PubMedCrossRefGoogle Scholar
  41. 41.
    Hachulla E, Launay D, Mouthon L, Sitbon O, Berezne A, Guillevin L, et al. French PAH-SSc Network. Is pulmonary arterial hypertension really a late complication of systemic sclerosis? Chest. 2009;136(5):1211–9.PubMedCrossRefGoogle Scholar
  42. 42.
    • Chung L, Liu J, Parsons L, Hassoun PM, McGoon M, Badesch DB, et al. Characterization of connective tissue disease-associated pulmonary arterial hypertension from REVEAL: identifying systemic sclerosis as a unique phenotype. Chest. 2010;138(6):1383–94. SSc-PAH was further identified as a unique phenotype due to much worse long-term prognosis compared with other forms of CTD-PAH.PubMedCrossRefGoogle Scholar
  43. 43.
    Fisher MR, Mathai SC, Champion HC, Girgis RE, Housten-Harris T, Hummers L, et al. Clinical differences between idiopathic and scleroderma-related pulmonary hypertension. Arthritis Rheum. 2006;54(9):3043–50.PubMedCrossRefGoogle Scholar
  44. 44.
    Mukerjee D, St George D, Coleiro B, Knight C, Denton CP, Davar J, et al. Prevalence and outcome in systemic sclerosis associated pulmonary arterial hypertension: application of a registry approach. Ann Rheum Dis. 2003;62(11):1088–93.PubMedCrossRefGoogle Scholar
  45. 45.
    Kawut SM, Taichman DB, Archer-Chicko CL, Palevsky HI, Kimmel SE. Hemodynamics and survival in patients with pulmonary arterial hypertension related to systemic sclerosis. Chest. 2003;123(2):344–50.PubMedCrossRefGoogle Scholar
  46. 46.
    Mathai SC, Hassoun PM. Pulmonary arterial hypertension in connective tissue diseases. Heart Fail Clin. 2012;8(3):413–25.PubMedCrossRefGoogle Scholar
  47. 47.
    Yang X, Mardekian J, Sanders KN, Mychaskiw MA, Thomas J 3rd. Prevalence of pulmonary arterial hypertension in patients with connective tissue diseases: a systematic review of the literature. Clin Rheumatol. 2013 Jun 20.Google Scholar
  48. 48.
    Prabu A, Patel K, Yee CS, Nightingale P, Situnayake RD, Thickett DR, et al. Prevalence and risk factors for pulmonary arterial hypertension in patients with lupus. Rheumatology (Oxford). 2009;48(12):1506–11.CrossRefGoogle Scholar
  49. 49.
    Lau CS, Yin G, Mok MY. Ethnic and geographical differences in systemic lupus erythematosus: an overview. Lupus. 2006;15(11):715–9.PubMedCrossRefGoogle Scholar
  50. 50.
    •• Jiang X, Humbert M, Jing ZC. Idiopathic pulmonary arterial hypertension and its prognosis in the modern management era in developed and developing countries. In: Humbert M, Souza R, Simonneau G, editors. Pulmonary Vascular Disorders. Prog Respir Res. Basel: Karger; 2012;85–93. The first description of the similarities and differences of baseline characteristics in Chinese PAH patients compared with those data from Western registries. Google Scholar
  51. 51.
    Jeon CH, Chai JY, Seo YI, Jun JB, Koh EM, Lee SK. Pulmonary hypertension study group of Korean College of Rheumatology. Pulmonary hypertension associated with rheumatic diseases: baseline characteristics from the Korean registry. Int J Rheum Dis. 2012;15(5):e80–9.PubMedCrossRefGoogle Scholar
  52. 52.
    Gunnarsson R, Andreassen AK, Molberg Ø, Lexberg ÅS, Time K, Dhainaut AS, et al. Prevalence of pulmonary hypertension in an unselected, mixed connective tissue disease cohort: results of a nationwide, Norwegian cross-sectional multicentre study and review of current literature. Rheumatology (Oxford). 2013;52(7):1208–13.CrossRefGoogle Scholar
  53. 53.
    Jais X, Launay D, Yaici A, Le Pavec J, Tchérakian C, Sitbon O, et al. Immunosuppressive therapy in lupus-and mixed connective tissue disease associated pulmonary arterial hypertension: a retrospective analysis of twenty-three cases. Arthritis Rheum. 2008;58(2):521–31.PubMedCrossRefGoogle Scholar
  54. 54.
    Launay D, Hachulla E, Hatron PY, Jais X, Simonneau G, Humbert M. Pulmonary arterial hypertension: a rare complication of primary Sjögren syndrome: report of 9 new cases and review of the literature. Medicine (Baltimore). 2007;86(5):299–315.CrossRefGoogle Scholar
  55. 55.
    van Loon RL, Roofthooft MT, Hillege HL, ten Harkel AD, van Osch-Gevers M, Delhaas T, et al. Pediatric pulmonary hypertension in the Netherlands. Epidemiology and characterization during the period 1991 to 2005. Circulation. 2011;124(16):1755–64.PubMedCrossRefGoogle Scholar
  56. 56.
    •• Berger RM, Beghetti M, Humpl T, Raskob GE, Ivy DD, Jing ZC, et al. Clinical features of paediatric pulmonary hypertension: a registry study. Lancet. 2012;379(9815):537–46. Baseline data from the TOPP registry, the first international, observational study that focused on pediatric pulmonary hypertension.PubMedCrossRefGoogle Scholar
  57. 57.
    Diller GP, Gatzoulis MA. Pulmonary vascular disease in adults with congenital heart disease. Circulation. 2007;115(8):1039–50.PubMedCrossRefGoogle Scholar
  58. 58.
    Mulder BJ. Changing demographics of pulmonary arterial hypertension in congenital heart disease. Eur Respir Rev. 2010;19(118):308–13.PubMedCrossRefGoogle Scholar
  59. 59.
    •• Duffels MG, Engelfriet PM, Berger RM, van Loon RL, Hoendermis E, Vriend JW, et al. Pulmonary arterial hypertension in congenital heart disease: an epidemiologic perspective from a Dutch registry. Int J Cardiol. 2007;120(2):198–204. This national registry gave us some new insights on the changing epidemiology of PAH related to congenital heart disease in Western countries.PubMedCrossRefGoogle Scholar
  60. 60.
    Vongpatanasin W, Brickner ME, Hillis LD, Lange RA. The Eisenmenger syndrome in adults. Ann Intern Med. 1998;128(9):745–55.PubMedCrossRefGoogle Scholar
  61. 61.
    Diller GP, Dimopoulos K, Broberg CS, Kaya MG, Naghotra US, Uebing A, et al. Presentation, survival prospects, and predictors of death in Eisenmenger syndrome: a combined retrospective and case-control study. Eur Heart J. 2006;27(14):1737–42.PubMedCrossRefGoogle Scholar
  62. 62.
    Lowe BS, Therrien J, Ionescu-Ittu R, Pilote L, Martucci G, Marelli AJ. Diagnosis of pulmonary hypertension in the congenital heart disease adult population impact on outcomes. J Am Coll Cardiol. 2011;58(5):538–46.PubMedCrossRefGoogle Scholar
  63. 63.
    Verheugt CL, Uiterwaal CS, van der Velde ET, Meijboom FJ, Pieper PG, van Dijk AP, et al. Mortality in adult congenital heart disease. Eur Heart J. 2010;31(10):1220–9.PubMedCrossRefGoogle Scholar
  64. 64.
    •• Dimopoulos K, Inuzuka R, Goletto S, et al. Improved survival among patients with Eisenmenger syndrome receiving advanced therapy for pulmonary arterial hypertension. Circulation. 2010;121(1):20–5. The first study identified the long-term benefits in patients with Eisenmenger’s syndrome from the PAH specific therapies.PubMedCrossRefGoogle Scholar
  65. 65.
    •• Manes A, Palazzini M, Leci E, Bacchi Reggiani ML, Branzi A, Galiè N. Current era survival of patients with pulmonary arterial hypertension associated with congenital heart disease: a comparison between clinical subgroups. Eur Heart J. 2013 Mar 1. The first study to compare the long-term survival among four types of PAH related to congenital heart disease. Interestingly, patients with left to right shunts and Eisenmenger’s syndrome have a much better 20-year rate of survival compared to that of patients with repaired congenital heart disease. Google Scholar
  66. 66.
    Speich R, Jenni R, Opravil M, Pfab M, Russi EW. Primary pulmonary hypertension in HIV infection. Chest. 1991;100(80):1268–71.PubMedCrossRefGoogle Scholar
  67. 67.
    Sitbon O, Lascoux-Combe C, Delfraissy JF, Yeni PG, Raffi F, De Zuttere D, et al. Prevalence of HIV-related pulmonary arterial hypertension in the current antiretroviral therapy era. Am J Respir Crit Care Med. 2008;177(1):108–13.PubMedCrossRefGoogle Scholar
  68. 68.
    Opravil M, Sereni D. Natural history of HIV-associated pulmonary arterial hypertension: trends in the HAART era. AIDS. 2008;22 suppl 3:S35–40.PubMedCrossRefGoogle Scholar
  69. 69.
    Opravil M, Pechere M, Speich R, Joller-Jemelka HI, Jenni R, Russi EW, et al. Natural history of HIV-associated pulmonary arterial hypertension: trends in the HAART era. Am J Respir Crit Care Med. 1997;155(3):990–5.PubMedCrossRefGoogle Scholar
  70. 70.
    Degano B, Guillaume M, Savale L, Montani D, Jais X, Yaici A, et al. HIV-associated pulmonary arterial hypertension: survival and prognostic factors in the modern therapeutic era. AIDS. 2010;24(1):67–75.PubMedCrossRefGoogle Scholar
  71. 71.
    McDonnell PJ, Toye PA, Hutchins GM. Primary pulmonary hypertension and cirrhosis: are they related? Am Rev Respir Dis. 1983;127(4):437–41.PubMedGoogle Scholar
  72. 72.
    Hadengue A, Benhayoun MK, Lebrec D, Benhamou JP. Pulmonary hypertension complicating portal hypertension: prevalence and relation to splanchnic hemodynamics. Gastroenterology. 1991;100(2):520–8.PubMedGoogle Scholar
  73. 73.
    Le Pavec J, Souza R, Herve P, Lebrec D, Savale L, Tcherakian C, et al. Portopulmonary hypertension: survival and prognostic factors. Am J Respir Crit Care Med. 2008;178(6):637–43.PubMedCrossRefGoogle Scholar
  74. 74.
    Krowka MJ, Swanson KL, Frantz RP, McGoon MD, Wiesner RH. Portopulmonary hypertension: results from a 10-year screening algorithm. Hepatology. 2006;44(6):1502–10.PubMedCrossRefGoogle Scholar
  75. 75.
    Ramsay MA, Simpson BR, Nguyen AT, Ramsay KJ, East C, Klintmalm GB. Severe pulmonary hypertension in liver transplant candidates. Liver Transpl Surg. 1997;3(5):494–500.PubMedCrossRefGoogle Scholar
  76. 76.
    Colle IO, Moreau R, Godinho E, Belghiti J, Ettori F, Cohen-Solal A, et al. Diagnosis of portopulmnonary hypertension in candidates for liver transplantation: a prospective study. Hepatology. 2003;37(2):401–9.PubMedCrossRefGoogle Scholar
  77. 77.
    • Krowka MJ, Miller DP, Barst RJ, Taichman D, Dweik RA, Badesch DB, et al. Portopulmonary hypertension: results from the US-based REVEAL Registry. Chest. 2012;141(4):906–15. Important clinical and prognostic information on PoPH in the modern management era was obtained from this prospective, multicenter registry.PubMedCrossRefGoogle Scholar
  78. 78.
    Krowka MJ, Plevak DJ, Findlay JY, Rosen CB, Wiesner RH, Krom RA. Pulmonary hemodynamics and perioperative cardiopulmonary-related mortality in patients with portopulmonary hypertension undergoing liver transplantation. Liver Transpl. 2000;6(4):443–50.PubMedCrossRefGoogle Scholar
  79. 79.
    Greiser E. Epidemiologic studies on the relation between use of appetite depressants and primary vascular pulmonary hypertension (in German). Internist (Berl). 1973;14(9):437–42.Google Scholar
  80. 80.
    Loogen F, Worth H, Schwan G, Goeckenjan G, Losse B, Horstkotte D. Long-term follow-up of pulmonary hypertension in patients with and without anorectic drug intake. Cor Vasa. 1985;27(2–3):111–24.PubMedGoogle Scholar
  81. 81.
    Brenot F, Hervé P, Petitpretz P, Parent F, Duroux P, Simonneau G. Primary pulmonary hypertension and fenfluramine use. Br Heart J. 1993;70(6):537–41.PubMedCrossRefGoogle Scholar
  82. 82.
    • Abenhaim L, Moride Y, Brenot F, Rich S, Benichou J, Kurz X, et al. Appetite-suppressant drugs and the risk of primary pulmonary hypertension. International Primary Pulmonary Hypertension Study Group. N Engl J Med. 1996;335(9):609–16. One of the most important studies that investigated the potential risk of primary pulmonary hypertension after exposure to appetite-suppressant drugs.PubMedCrossRefGoogle Scholar
  83. 83.
    Rich S, Rubin L, Walker AM, Schneeweiss S, Abenhaim L. Anorexigens and pulmonary hypertension in the United States: results from the surveillance of North American pulmonary hypertension. Chest. 2000;117(3):870–4.PubMedCrossRefGoogle Scholar
  84. 84.
    Souza R, Humbert M, Sztrymf B, Jaïs X, Yaïci A, Le Pavec J, et al. Pulmonary arterial hypertension associated with fenfluramine exposure: report of 109 cases. Eur Respir J. 2008;31(2):343–8.PubMedCrossRefGoogle Scholar
  85. 85.
    Rich S, Shillington A, McLaughlin V. Comparison of survival in patients with pulmonary hypertension associated with fenfluramine to patients with primary pulmonary hypertension. Am J Cardiol. 2003;92(11):1366–8.PubMedCrossRefGoogle Scholar
  86. 86.
    Montani D, Bergot E, Günther S, Savale L, Bergeron A, Bourdin A, et al. Pulmonary arterial hypertension in patients treated by dasatinib. Circulation. 2012;125(17):2128–37.PubMedCrossRefGoogle Scholar
  87. 87.
    Seferian A, Chaumais MC, Savale L, Günther S, Tubert-Bitter P, Humbert M, et al.. Drugs induced pulmonary arterial hypertension. Presse Med. 2013 Aug 21.Google Scholar
  88. 88.
    Lapa MDB, Jardim C, Fernandes CJ, Dourado PM, Figueiredo M, Farias A, et al. Cardiopulmonary manifestations of hepatosplenic schistosomiasis. Circulation. 2009;119(11):1518–23.PubMedCrossRefGoogle Scholar
  89. 89.
    Lapa MSFE, Jardim C, Martins Bdo C, Arakaki JS, Souza R. Clinical characteristics of pulmonary hypertension patients in two reference centers in the city of Sao Paulo (in Portuguese). Rev Assoc Med Bras. 2006;52(3):139–43.PubMedCrossRefGoogle Scholar
  90. 90.
    dos Santos Fernandes CJ, Jardim CV, Hovnanian A, Hoette S, Dias BA, Souza S, et al. Survival in schistosomiasis-associated pulmonary arterial hypertension. J Am Coll Cardiol. 2010;56(9):715–20.PubMedCrossRefGoogle Scholar
  91. 91.
    Wagenvoort CA, Beetstra A, Spijker J. Capillary haemangiomatosis of the lungs. Histopathology. 1978;2(6):401–6.PubMedCrossRefGoogle Scholar
  92. 92.
    Montani D, Price LC, Dorfmuller P, Achouh L, Jaïs X, Yaïci A, et al. Pulmonary veno-occlusive disease. Eur Respir J. 2009;33(1):189–200.PubMedCrossRefGoogle Scholar
  93. 93.
    Montani D, Achouh L, Dorfmüller P, Le Pavec J, Sztrymf B, Tchérakian C, et al. Pulmonary veno-occlusive disease: clinical, functional, radiologic, and hemodynamic characteristics and outcome of 24 cases confirmed by histology. Medicine (Baltimore). 2008;87(4):220–33.CrossRefGoogle Scholar
  94. 94.
    Jing ZC, Xu XQ, Han ZY, Wu Y, Deng KW, Wang H, et al. Registry and survival study in chinese patients with idiopathic and familial pulmonary arterial hypertension. Chest. 2007;132(2):373–9.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  1. 1.Thrombosis Medicine Center, State Key Laboratory of Cardiovascular Disease, Fu Wai HospitalPeking Union Medical College and Chinese Academy of Medical SciencesBeijingChina

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