Pulmonary hypertension (PH) refers to the elevation of blood pressure in the pulmonary arteries. PAH is a subgroup of PH caused by the narrowing of these blood vessels.

PAH describes a subgroup of patients with PH due to increased pulmonary vascular resistance (PVR) caused by pathological changes to the blood vessels in the lungs. Most PH is not PAH, and in these cases PH is usually as a result of other diseases such as heart or lung disease which raise the pulmonary artery pressure (PAP) by other mechanisms.1



PH is categorised into five main groups, according to clinical presentation and aetiology:1

Group 1. PAH

  1. 1.1 Idiopathic (IPAH)
  2. 1.2 Heritable (HPAH)
    1. 1.2.1 Bone morphogenetic protein receptor type 2 (BMPR2) mutation
    2. 1.2.2 Other mutations
  3. 1.3 Drugs and toxins induced
  4. 1.4 Associated with:
    1. 1.4.1 Connective tissue disease (CTD)
    2. 1.4.2 Human immunodeficiency virus (HIV) infection
    3. 1.4.3 Portal hypertension (PoPH)
    4. 1.4.4 Congenital heart disease (CHD)
    5. 1.4.5 Schistosomiasis
  5. 1.' Pulmonary veno-occlusive disease (PVOD) and/or pulmonary capillary haemangiomatosis
  6. 1." Persistent PH of the newborn (PPHN)

Group 2. PH due to left heart disease

  1. 2.1 Left ventricular systolic dysfunction
  2. 2.2 Left ventricular diastolic dysfunction
  3. 2.3 Valvular disease
  4. 2.4 Congenital/acquired left heart inflow/outflow tract obstruction and congenital cardiomyopathies
  5. 2.5 Congenital/acquired pulmonary veins stenosis

Group 3. PH due to lung disease or hypoxia

  1. 3.1 Chronic obstructive pulmonary disease (COPD)
  2. 3.2 Interstitial lung disease (ILD)
  3. 3.3 Other pulmonary diseases with mixed restrictive and obstructive pattern
  4. 3.4 Sleep-disordered breathing
  5. 3.5 Alveolar hypoventilation disorders
  6. 3.6 Chronic exposure to high altitude
  7. 3.7 Developmental lung diseases

Group 4. Chronic thromboembolic pulmonary hypertension (CTEPH) and other pulmonary artery obstructions

  1. 4.1 Chronic thromboembolic pulmonary hypertension
  2. 4.2 Other pulmonary artery obstructions

Group 5. PH with unclear or multifactorial mechanisms

  1. 5.1 Haematological disorders
  2. 5.2 Systemic disorders
  3. 5.3 Metabolic disorders
  4. 5.4 Other

Comparative data on the prevalence of the different types of PH are not widely available; however, PH due to left heart disease (Group 2) is believed to be the most common.1 The different types of PAH (Group 1) are discussed below.




is one of the more common forms of PAH, accounting for 30–50% of all cases of PAH.2 IPAH describes sporadic disease in which there is neither a family history of PAH nor an identified risk factor.1


accounts for at least 6% of cases of PAH.3 Mutations in the bone morphogenetic protein receptor 2 (BMPR2) have been identified in the majority of cases.4


may develop as a rare side effect of certain drugs and toxins, notably anorexigenic agents, such as fenfluramine.1 As a result, some of these agents are no longer available and it is likely that the incidence of drug-induced PAH will decrease.5


is PAH accompanying a number of other conditions, which together account for most other cases. These conditions include CTD, HIV, CHD, portal hypertension and schistosomiasis – these are discussed below.1


Figure 1. Proportion of patients with different subcategories of PAH (US registry 2006–2007, n=2525).6 Adapted from Badesch, Chest 2010

In registries, around a third to a half of all PAH patients have idiopathic, heritable or drug-induced PAH. In the group of associated PAH conditions, the leading cause is CTD (most commonly systemic sclerosis [SSc]).1



  • CTDs are systemic autoimmune diseases that commonly cause the formation of scar tissue (fibrosis) within the connective tissue that surrounds, supports and protects organs, including vascular tissue. PAH is a well-recognised complication of CTDs, such as SSc and systemic lupus erythematosus (SLE), and is the second most prevalent type of PAH after IPAH in Western countries1
  • The prevalence of PAH in patients with CTDs has been well established only for patients with SSc.1 The prevalence of PAH in patients with SSc is between 5% and 40%, with a mean from several studies of 16%.7 PAH is a leading cause of death in these patients8
  • Patients with PAH associated with SSc have a particularly poor prognosis compared with patients with IPAH, with a three-fold increased risk of death.8 This may be due to difficulties in diagnosis alongside other comorbidities, and the relatively poor response to treatment compared with IPAH8,9
  • Click here to learn more about PAH in CTD and the different screening strategies that can be employed

Figure 2. Organ involvement in systemic sclerosis


  • CHD is relatively common and affects around 4–50 per thousand live births10
  • Approximately 5–10% of adults with CHD will go on to develop PAH11 and this subgroup represents around 10–23% of all cases of PAH2
  • The demographics of PAH-CHD are changing, with more patients with CHD surviving to adulthood due to advances in cardiovascular surgery12
  • PAH-CHD represents a heterogeneous patient population, and it is important to distinguish between the underlying cardiac defects12
  • The most severe form of PAH-CHD is Eisenmenger’s syndrome (ES), which is associated with the complete or partial reversal of an initial left-to-right shunt to a right-to-left shunt, causing cyanosis and limited exercise capacity. Not all patients with PAH-CHD develop ES
  • Patients with PAH associated with CHD also include those with mild to moderate systemic-to-pulmonary shunts with no cyanosis at rest, patients with small defects and those with residual PAH following corrective cardiac surgery1
  • Click here to learn about the challenges faced by physicians in the management of adult CHD patients in the UK


  • PAH is a rare but relatively well-documented complication of HIV infection (estimated prevalence in patients with HIV being 0.5%)13
  • Following the advent of highly active anti-retroviral therapy (HAART) and markedly improved survival rates in HIV patients, PAH and other non-infectious manifestations are increasingly responsible for HIV-associated morbidity and poor prognosis14
  • Although the reasons for the development of PAH in patients with HIV infection are not yet fully understood, histopathology suggests that an indirect action of viral infection on inflammation and growth factors may act as a trigger in a predisposed patient1
  • HIV-associated PAH shows a similar clinical picture to IPAH,1 although unlike IPAH, cases of reversible disease have been seen in a substantial number of patients following PAH therapy15


  • PAH is a well-recognised complication of portal hypertension, and cirrhotic liver disease is by far the most common cause of this1
  • PAH associated with portal hypertension (also called portopulmonary hypertension [PoPH]) occurs in approximately 1–5% of patients with portal hypertension1 and represents around 10% or less of the PAH population6,16
  • In general, the signs and symptoms of PAH associated with portal hypertension are similar or identical to other forms of PAH1


  • Schistosomiasis is a parasitic disease caused by trematode flatworms of the genus Schistosoma
  • It is estimated that over 200 million people are infected by species of Schistosoma17 and globally, schistosomiasis-associated PAH represent an important burden to mankind1
  • Patients with schistosomiasis and PAH can have the required specific clinical and pathological characteristics to be included in the APAH group. The prevalence of PAH in patients with schistosomiasis is estimated at 5%17
  • Africa is the geographic area most affected by Schistosomiasis18 and PAH-associated schistosomiasis is rare in Europe6

Click here for more information about the treatment and prognosis of these conditions.


  1. Galiè N, et al. Eur Heart J 2016;37:67–119
  2. Lau E, et al. Nat Rev Cardiol 2017;14:603–14
  3. Lane K, et al. Nature Genetics 2000;26:81–4
  4. Morrell NW. Biol Rep 2010;2.pii:22
  5. Jesus Perez VA, et al. Adv Pulmon Hypertens 2017;15:133–7
  6. Badesch DB, et al. Chest 2010;137:376–87
  7. McGoon M, et al. Chest 2014;126:14S–34S
  8. Chaisson N and Hassoun P. Chest 2013;144:1346–56
  9. Avouac J, et al. Ann Rheum Dis 2008;67:808–14
  10. Hoffman J, et al. J Am Coll Cardiol 2002;39:1890–900
  11. Diller G and Gatzoulis M. Circulation 2007;115:1039–50
  12. Van Dissel A, et al. J Clin Med 2017;6(4) pii:E40
  13. Sitbon O, et al. Am J Respir Crit Care Med 2008;177:108–13
  14. Sitbon O. AIDS 2008;22(Suppl 3):S55–62
  15. Simonneau G, et al. J Am Coll Cardiol 2013;62:D34–41
  16. Humbert M, et al. Am J Respir Crit Care Med 2006;173:1023–30
  17. Lapa M, et al. Circulation 2009;119:1518–23
  18. Demosthenes G, et al. Pulm Circ 2014;4:596–611

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