Pulmonary arterial hypertension (PAH) is a progressive disease caused by narrowing or tightening (constriction) of the pulmonary arteries, which connect the right side of the heart to the lungs. Untreated, PAH is a disease with a very poor prognosis.

By definition, PAH is characterized by an increase in mean pulmonary arterial pressure (PAP) to ≥25mmHg at rest, and a mean primary capillary wedge pressure of ≤15 mmHg.

WORLD HEALTH ORGANIZATION PULMONARY HYPERTENSION CLASSIFICATION

Pulmonary arterial hypertension (PAH) represents Group 1 within the Pulmonary Hypertension World Health Organisation (WHO) clinical classification system (Dana Point 2008) and is one of five such groups. The groups are divided based on etiology as shown in the following table.

   

Group 1

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Pulmonary Arterial Hypertension (PAH)

  • Idiopathic (IPAH)
  • Heritable (HPAH)
    • Bone morphogenetic protein receptor type 2 (BMPR2)
    • Activin receptor-like kinase 1 gene (ALK1), endoglin (with or without haemorrhagic telangiectasia)
    • Unknown
  • Drug- and toxin-induced
  • Associated with (APAH):
    • Connective tissue diseases
    • Human immunodeficiency virus (HIV) infection
    • Portal hypertension
    • Congenital heart disease (CHD)
    • Schistosomiasis
    • Chronic haemolytic anaemia
  • Persistent pulmonary hypertension of the newborn (PPHN) 
Group 1' 

Pulmonary veno-occlusive disease (PVOD) and/or pulmonary capillary haemangiomatosis (PCH) 

Group 2 

  

 

Pulmonary hypertension due to left heart diseases

  • Systolic dysfunction
  • Diastolic dysfunction
  • Valvular disease 

Group 3  

 

 

 

 

 

 

 

 

 

Pulmonary hypertension due to lung diseases and/or hypoxemia

  • Chronic obstructive pulmonary disease (COPD)
  • Interstitial lung disease (ILD)
  • Other pulmonary diseases with mixed restrictive and obstructive pattern
  • Sleep-disordered breathing
  • Alveolar hypoventilation disorders
  • Chronic exposure to high altitude
  • Developmental abnormalities 
Group 4 

Chronic thromboembolic pulmonary hypertension (CTEPH) 

Group 5  

 

 

 

 

 

 

 

 

PH with unclear multifactorial mechanisms

  • Haematological disorders: myeloproliferative disorders, splenectomy
  • Systemic disorders: sarcoidosis, pulmonary Langerhans cell histiocytosis, lymphangioleiomyomatosis, neurofibromatosis, vasculitis
  • Metabolic disorders: glycogen storage disease, Gaucher disease, thyroid disorders
  • Others: tumoral obstruction, fibrosing mediastinitis, chronic renal failure on dialysis 

Although Pulmonary arterial hypertension (PAH) is a rare disease, with an estimated prevalence of 
15-50 cases per million, the prevalence of PAH in certain at-risk groups is substantially higher. For example, in HIV-infected patients the prevalence is 0.5%, in patients with systemic sclerosis it has been reported to be 7-12%, and in patients with sickle cell disease the prevalence is around 2-3.75%.

Idiopathic PAH (IPAH), one of the more common forms of PAH, has an annual incidence of 1-2 cases per million people in the US and Europe and is 2-4 times as common in women as in men. The mean age at diagnosis is around 45 years, although the onset of symptoms can occur at any age. Despite the true relative prevalence of IPAH, heritable PAH (HPAH), and associated PAH (APAH) being unknown, it is likely that IPAH accounts for at least 40% of cases of PAH, with APAH accounting for the majority of the remaining cases.