Pulmonary arterial hypertension (PAH) is a type of pulmonary hypertension that causes high blood pressure in the small arteries of the lungs. It is a serious condition that can impair blood flow, causing symptoms like shortness of breath, chest pain, and light-headedness that affect daily life.

In some cases, the cause of PAH is unclear, or it is caused by heart or lung diseases or by certain drugs and infections.

1. Idiopathic PAH

About half of PAH cases have no known cause. When a condition’s cause is unknown, it’s called idiopathic. Idiopathic PAH is the most common type of PAH. While the exact cause of idiopathic PAH is not known, experts believe environmental triggers and genetics may play a role.

2. Connective Tissue Disease

The second most common type of PAH is caused by connective tissue disease. These conditions are autoimmune, meaning the body’s immune system attacks itself. Researchers believe that the inflammatory response of these autoimmune conditions affects the arteries in the lungs.

The following conditions are linked to PAH:

• Systemic sclerosis: A type of scleroderma that causes a hardening and tightening of skin connective tissue within the body
• Systemic lupus erythematosus (SLE): The most common type of lupus (an autoimmune disease) that causes inflammation that damages connective tissues (cartilage and the lining of the blood vessels)
• Mixed connective tissue disease: A rare condition that overlaps with other connective tissue diseases

3. Congenital Heart Disease

Congenital heart disease is an abnormality of the heart that is present from birth. When the heart does not form properly, it can lead to abnormal blood flow in the heart and lungs.

The following congenital heart conditions can cause PAH:

• Atrial septal defect (ASD): Hole connecting the upper chambers of the heart
• Anomalous pulmonary venous return: Abnormal connection of the veins that bring blood back from the lungs to the heart
• Ventricular septal defect (VSD): Hole connecting the bottom chambers of the heart
• Atrioventricular septal defect: A hole involving both the upper and lower chambers and the valves between them
• Transposition of the great arteries (TGA): The aorta and main pulmonary artery are switched and connected to the wrong side of the heart

4. Inherited PAH

Up to 20% of people with PAH have an inherited form of the disease. For example, changes in the BMPR2 gene can be passed down in families. When one parent has the mutation, the child has a 50% chance of inheriting it. However, even with the mutation, the children will not necessarily have PAH.

Only 20% of people with a known genetic mutation in the BMPR2 gene will show signs of PAH, suggesting that other factors are involved.

5. PAH Due to Drugs or Toxins

Drugs and toxins can damage the arteries in the lungs, leading to PAH. The following may cause PH:

• Appetite suppressants: Propan (phenylpropanolamine), Apiquel (aminorex), Redux (dexfenfluramine) (no longer prescribed due to safety concerns)
• Fenfluramine: Previously used as an appetite suppressant, now only approved in restricted cases for the treatment of certain seizure disorders
• Amphetamines, methamphetamines, and cocaine: Increases heart rate to dangerous levels and lead to heart disease
• Certain cancer drugs: Sprycel (dasatinib), Bosulif (bosutinib), and alkylating agents
• Immune-modulating drugs: lnterferon-alpha and interferon-beta and leflunomide
• Herbs and supplements: Saint-John’s-wort and L-tryptophan
• Hepatitis C treatments: Sofosbuvir-based therapy

6. PAH Due to Liver Disease

Certain types of liver disease, like cirrhosis, can cause high blood pressure in the blood vessels to the liver, known as portal hypertension. This can, in turn, lead to a type of PAH called portopulmonary hypertension. While the exact cause is unclear, researchers suggest that certain harmful compounds typically filtered in the liver bypass the liver and reach the lungs.

7. PAH Due to Infection

Less commonly, infections from viruses and parasites can affect the pulmonary arteries, leading to PAH. These include:

• Human immunodeficiency virus (HIV): For every 200 people with HIV, an estimated 1 to 10 will have PAH
• Parasitic infection, such as schistosomiasis: Researchers believe the worm eggs go to the lungs, causing inflammation and scarring
• Hepatitis B and C viruses: Less common cause of PAH
• Human herpesvirus 8: A type of herpesvirus

Who Is More Likely to Develop PAH? 

In addition to the causes listed above, PAH is more likely to affect people:

• Ages 30 to 60
• With a family history of PAH
• With genetic conditions, such as BMPR2 gene mutation, Down syndrome (trisomy 21) and Gaucher disease
• Who use drugs like cocaine and methamphetamines
• Living at high altitudes

What Causes Life-Threatening Complications? 

PAH is a serious and life-threatening condition that can worsen over time. When the blood pressure in the lungs is elevated, it strains the heart and alters blood flow. This can lead to issues like:

• Low blood counts (anemia) due to poor iron absorption
• Abnormal heart rhythms (arrhythmias) due to abnormal heart pressures
• Blood clots in the lungs due to impaired blood flow
• Bleeding in the lungs due to the high pressure
• Heart failure due to strain on the heart and abnormal blood flow

Summary

Pulmonary arterial hypertension (PAH) is a subtype of pulmonary hypertension (PH) that causes high blood pressure in the small arteries of the lungs. Often, the cause of PAH is unknown (idiopathic). However, other causes of PAH include conditions such as connective tissue disease, liver disease, congenital heart disease, genes, drugs and toxins, or infection.