Description

• Pulmonary arterial hypertension (PAH) is a category of pulmonary hypertension (PH) characterized by abnormalities in the small pulmonary arteries (pre-capillary PH) that produce increased pulmonary arterial pressure (PAP) and vascular resistance, eventually resulting in right-sided heart failure. PAH is a progressive disorder associated with increased mortality:
  • PAH is defined by (1):
    • Mean PAP ≥25 mm Hg at rest
    • Pulmonary capillary wedge pressure ≤15 mm Hg
  • Classified as primary [without cause: Now idiopathic pulmonary arterial hypertension (IPAH)] or secondary [with cause or associated condition]
  • Also classified into 5 main categories:
    • Idiopathic: Sporadic, with no family history or risk factors
    • Heritable: IPAH with mutations or familial cases with or without mutations
    • Drug or toxin induced: Mostly associated with anorectics
    • Associated: Connective tissue diseases (e.g., systemic lupus erythematosus, rheumatoid arthritis, scleroderma); HIV infection; portal hypertension; congenital heart disease; schistosomiasis; chronic hemolytic anemia (e.g., sickle cell disease)
    • Persistent PH of the newborn
• System(s) affected: Pulmonary; Cardiovascular

Epidemiology

• Age: Can occur at any age; mean age, 37 years
• Sex (IPAH): Female > Male (~2:1)

• IPAH: Low, ~2–6 per million
• Drug-induced PAH: 1/25,000 with >3 months of anorectic use
• HIV associated: 0.5/100
• Portal hypertension associated: 1–6/100
• Scleroderma associated: 6–60%

• PAH: ~15–50 cases per million
• IPAH: ~6 cases per million

Risk Factors

• Female sex
• Previous anorectic drug use
• Recent acute pulmonary embolism
• Commonly associated conditions
• 1st-degree relatives of patient with familial PAH

• 75% of heritable pulmonary arterial hypertension (HPAH) cases and 25% of IPAH cases have mutations in BMPR2 (autosomal dominant)
• Mutations in ALK1 and endoglin (autosomal dominant) also are associated with PAH.

Pathophysiology

• Pulmonary: Inflammation, vasoconstriction, endothelial dysfunction, and remodeling of pulmonary arteries produced by increased cell proliferation and reduced rates of apoptosis lead to obstruction.
• Cardiovascular: Right ventricular hypertrophy (RVH), eventually leading to right-sided heart failure

Etiology

• IPAH: By definition, unknown. True IPAH is mostly sporadic or sometimes familial in nature.
• Pulmonary arteriolar hyperactivity and vasoconstriction, occult thromboembolism, or autoimmune (high frequency of antinuclear antibodies)

Commonly Associated Conditions

See Associated PAH, above.