What Is the Main Cause of Pulmonary Hypertension?

Pulmonary hypertension, or high blood pressure in the blood vessels that feed the lungs, can be deadly.

Pulmonary hypertension, also called pulmonary arterial hypertension (PAH), is a rare form of abnormally high blood pressure that affects the arteries of the lungs and the right side of the heart. Pulmonary hypertension can be life-threatening if it is left untreated.

Symptoms of pulmonary arterial hypertension include: 

• Shortness of breath upon exertion 
• Fatigue 
• Chest pain 
• Lethargy 
• Lightheadedness/fainting with exertion 
• Loss of appetite 
• Right upper quadrant pain 
• Palpitations
• Swelling of feet and ankles (edema)
• Blue lips and fingers
• Cough
• Vomiting blood
• Hoarseness 

The cause of pulmonary arterial hypertension is unknown. It is believed the disease may be caused by damage to the cells that line the arteries of the lungs. If there is no known cause for the damaged cells, it is called idiopathic pulmonary arterial hypertension. In some cases, the damaged cells are believed to be caused by a genetic mutation, and it is called heritable pulmonary arterial hypertension.

Some medical conditions are associated with the development of pulmonary arterial hypertension, including:

• Autoimmune disorders such as scleroderma, lupus, rheumatoid arthritis, and others
• Lung diseases such as chronic bronchitis, emphysema, and pulmonary fibrosis
• Blood clots in the lungs
• Exposure to certain toxins and drugs
• Illegal drug use, including methamphetamine and cocaine
• Infections, including HIV and schistosomiasis
• Cirrhosis of the liver
• Congenital heart abnormalities
• Congestive heart failure
• Sleep apnea

The diagnosis of pulmonary arterial hypertension is made with a history and physical examination. 

Lab studies that may be used to diagnose pulmonary arterial hypertension include:

• Complete blood (CBC) count
• Biochemistry panel
• Prothrombin time (PT)
• Activated partial thromboplastin time (aPTT) 
• Arterial blood gas determinations
• Antinuclear antibody (ANA) levels
• Rheumatoid factor (RF) 
• Antineutrophil cytoplasmic antibody (ANCA). 
• Anti-Scl-70, anticentromere, and anti-U1-RNP antibodies (if scleroderma is suspected)
• Liver function tests, as well as markers of synthetic function (i.e., albumin, international normalized ratio [INR])
• Platelet levels 
• Brain natriuretic peptide (BNP of NT-proBNP) 
• HIV testing
• Hepatitis serology tests
• Urine toxicology screening
• Screening for gene mutations such as BMPR2 if heritable pulmonary arterial hypertension is suspected
• Iron studies 

Imaging studies that may be used to diagnose pulmonary arterial hypertension include:

• Chest radiography 
• Computed tomography (CT) scan
• Heart studies that may be used to diagnose pulmonary arterial hypertension include:
• Electrocardiography (ECG)
• Echocardiography
• Doppler echocardiography

Other studies that may be used to diagnose pulmonary arterial hypertension include:

• Ventilation-perfusion scanning 
• Pulmonary function testing
• Polysomnography for sleep-disordered breathing
• Right-sided heart catheterization

Treatments for pulmonary arterial hypertension (PAH) are aimed at slowing the progression of the disease, relieving symptoms, and improving quality of life. 

Supportive treatments for pulmonary arterial hypertension include:

• Oxygen therapy
• Diuretics
  • Loop diuretics such as furosemide and bumetanide are first line
  • Aldosterone antagonists are considered as adjunctive agents
• Digoxin
• Exercise
• Anticoagulation
  • Warfarin remains the anticoagulant of choice
  • There is limited experience in PAH with the newer oral anticoagulants such as dabigatran, rivaroxaban, and apixaban
• Other medications 
  • Endothelin receptor antagonists (ambrisentan, bosentan, and macitentan)
  • Phosphodiesterase-5 (PDE-5) inhibitors (sildenafil, tadalafil, vardenafil) and guanylate cyclase stimulators (riociguat)
  • Prostacyclin analogues (beraprost, epoprostenol, iloprost, treprostinil) and prostacyclin receptor agonists (selexipag)

Other treatments for pulmonary arterial hypertension include:

• Vasodilatory therapies (used to help widen the blood vessels) 
• Balloon atrial septostomy 
• Lung transplantation (reserved for severe cases) 
• Heart-lung transplantation in patients with PAH due to congenital cardiac disease or severe left ventricular dysfunction
• Vaccinations against influenza and pneumococcal pneumonia to decrease the risk of developing pneumonia are recommended 

Long-term monitoring of pulmonary arterial hypertension is recommended following diagnosis.

• Six-minute walk distance (6MWD) testing should be performed at least twice yearly
• Transthoracic echocardiography may be performed at least once per year
• Right-sided heart catheterization may be considered in patients who have a change in clinical status

Complications of pulmonary arterial hypertension include:

• Right-sided heart failure
• Sudden cardiac death
• Pulmonary artery dissection and rupture, coughing up blood (massive hemoptysis), and left main compression syndrome
• Supraventricular and, less commonly ventricular, arrhythmias (irregular heart rates)

There is a high mortality rate associated with pregnancy in patients with PAH. Females of reproductive potential are advised to use birth control.

The life expectancy for patients with pulmonary arterial hypertension (PAH) varies and depends on the cause, severity, and treatment.

There is a 5-year survival rate for pulmonary arterial hypertension of 57% without treatment which means 57% of patients are alive 5 years following the time of diagnostic right-sided heart catheterization. For example, life expectancy for patients with right-sided heart failure is approximately 1 year following diagnosis without treatment.

Pneumonia is the cause of death in about 7% of patients with PAH, so vaccinations against influenza and pneumococcal pneumonia are recommended.

Factors that contribute to a poorer prognosis include:

• Male sex
• Age older than 50 years
• Worse WHO functional status
• Right ventricular dysfunction 

Most cases of pulmonary arterial hypertension (PAH) cannot be prevented. Avoiding certain risk factors may help reduce the risk of developing the disease in some cases.

• Avoid using appetite suppressants 
• Do not use illegal stimulants such as amphetamine-derivatives and cocaine
• Do not smoke
• Make sure obstructive sleep apnea or another lung disease is well-managed