The WHO classification system divides pulmonary hypertension into five clinical groups based on the underlying cause. Each group shares similar mechanisms of disease and responds to different treatment strategies, which is why getting the classification right matters so much for management. The system has been refined at multiple world symposia over the years, and the most recent major update came in the 2022 ESC/ERS guidelines, which lowered the pressure threshold used to define pulmonary hypertension from 25 mmHg to greater than 20 mmHg.
How the Five Groups Are Organized
The classification exists because “pulmonary hypertension” is not a single disease. It is a hemodynamic state, meaning abnormally high pressure in the blood vessels of the lungs, that can result from dozens of different conditions. Grouping those conditions by their shared biology helps clinicians choose the right treatment. A medication that works well for Group 1, for example, can be ineffective or even harmful in Group 2.
The five groups are:
- Group 1: Pulmonary arterial hypertension (PAH)
- Group 2: Pulmonary hypertension due to left heart disease
- Group 3: Pulmonary hypertension due to lung disease or chronic low oxygen levels
- Group 4: Chronic thromboembolic pulmonary hypertension (CTEPH)
- Group 5: Pulmonary hypertension with unclear or multifactorial causes
Group 1: Pulmonary Arterial Hypertension
Group 1 is what most people mean when they say “PAH.” The problem originates in the small arteries of the lungs themselves. These vessels narrow, stiffen, and sometimes develop scar-like changes that progressively increase resistance to blood flow. The right side of the heart has to pump harder and harder to push blood through, and over time it can weaken and fail.
Several distinct conditions fall under this umbrella. Idiopathic PAH has no identifiable cause. Heritable PAH runs in families, typically linked to specific gene mutations. PAH can also develop in association with connective tissue diseases like scleroderma, congenital heart defects that create abnormal blood flow between heart chambers, liver cirrhosis with portal hypertension, HIV infection, and exposure to certain drugs such as amphetamines or older appetite suppressants. Schistosomiasis, a parasitic infection common in parts of Africa and South America, is another recognized trigger.
Hemodynamically, Group 1 is defined as pre-capillary pulmonary hypertension: mean pulmonary artery pressure above 20 mmHg, a wedge pressure of 15 mmHg or below (indicating the left side of the heart is not the source of the problem), and pulmonary vascular resistance greater than 2 Wood units. Most of the targeted pulmonary hypertension therapies on the market today were developed specifically for this group.
Group 2: Left Heart Disease
Group 2 is the most common form of pulmonary hypertension in Western countries. The elevated lung pressures here are a downstream consequence of problems on the left side of the heart. When the left ventricle or the mitral and aortic valves are not working properly, blood backs up into the lungs and raises pressure in the pulmonary vessels.
Heart failure is the most frequent driver. This includes both heart failure with reduced pumping strength and heart failure with preserved pumping strength (sometimes called HFpEF). The prevalence of HFpEF has been rising significantly as the population ages and more people survive heart attacks and other cardiovascular events. Left-sided valvular disease, particularly involving the mitral valve, is another common cause.
Distinguishing Group 2 from Group 1 is one of the trickiest challenges in this field, especially in patients with HFpEF. Both can present with similar symptoms, including shortness of breath and exercise intolerance. The key difference shows up during right heart catheterization: in Group 2, the wedge pressure is above 15 mmHg, reflecting the backup of blood from the left heart. Treatment focuses on managing the underlying heart condition rather than using PAH-specific medications.
Group 3: Lung Disease and Low Oxygen
Chronic lung diseases are increasing in prevalence worldwide, and the pulmonary hypertension that accompanies them falls into Group 3. The mechanism involves chronic low oxygen levels and, in many cases, destruction or scarring of the lung’s blood vessel network.
COPD is the most common obstructive lung disease linked to Group 3 and ranks as the third leading cause of death in the United States. Restrictive lung diseases also contribute, particularly idiopathic pulmonary fibrosis, combined pulmonary fibrosis and emphysema, and interstitial lung diseases tied to connective tissue disorders or chronic hypersensitivity pneumonitis.
The group also covers conditions beyond classic lung disease. Sleep-disordered breathing, including obstructive sleep apnea and obesity hypoventilation syndrome, can raise pulmonary pressures over time. Chronic exposure to high altitude causes sustained low oxygen that remodels lung blood vessels. Developmental lung disorders like bronchopulmonary dysplasia, which affects premature infants, are included as well. There are limited approved therapies specifically for Group 3 PH, and treatment generally centers on managing the underlying lung condition and correcting oxygen levels.
Group 4: Chronic Blood Clots in the Lungs
Group 4, or CTEPH, develops when blood clots in the pulmonary arteries fail to dissolve completely after a pulmonary embolism. The leftover clot material organizes into scar tissue that physically obstructs blood flow, and the surrounding small vessels can develop secondary disease as well. The result is a progressive condition marked by worsening exercise intolerance.
What makes Group 4 stand apart from the other groups is that it is potentially curable. A surgical procedure called pulmonary endarterectomy can remove the organized clot material from the vessel walls. Not every patient is a candidate for surgery, depending on where the clots are located and other health factors, but for those who are, outcomes can be excellent.
Diagnosis requires specific hemodynamic criteria (mean pulmonary artery pressure above 20 mmHg, wedge pressure at or below 15 mmHg, and pulmonary vascular resistance above 2 Wood units) plus imaging evidence of chronic clot material. A ventilation/perfusion scan is the initial screening tool because a normal result essentially rules out CTEPH. Right heart catheterization with pulmonary angiography remains the gold standard for confirming the diagnosis, since a negative CT scan alone cannot exclude it.
Group 5: Unclear or Multifactorial Causes
Group 5 is a catch-all for conditions that cause pulmonary hypertension through mechanisms that do not fit neatly into the other four groups, often involving more than one pathway at once. It has been called “the orphan’s orphan disease” because these conditions are individually rare and collectively understudied.
The group is subdivided into three categories. Hematologic disorders include myeloproliferative diseases (such as polycythemia vera and primary myelofibrosis), chronic hemolytic anemias like sickle cell disease and thalassemia, and post-splenectomy states. Systemic disorders include sarcoidosis and pulmonary Langerhans cell histiocytosis, both of which can affect lung vessels through complex inflammatory and structural changes. Metabolic disorders round out the group, including thyroid disease, glycogen storage diseases, and Gaucher disease.
Because the mechanisms differ so much from one Group 5 condition to another, there is no unified treatment approach. Management targets the specific underlying disorder.
How Doctors Determine Your Group
Assigning a WHO group is not a single-test process. It involves a structured workup that systematically rules conditions in or out. An echocardiogram is typically the first step, estimating lung pressures and evaluating left heart function. If pulmonary hypertension is suspected, further testing branches out: pulmonary function tests and arterial blood gas analysis assess lung disease, a ventilation/perfusion scan screens for chronic clots, and CT imaging evaluates lung tissue and blood vessels.
Right heart catheterization is the definitive test. A thin catheter threaded through a vein into the right side of the heart directly measures mean pulmonary artery pressure, wedge pressure, and pulmonary vascular resistance. These three numbers separate pre-capillary PH (Groups 1, 3, 4, and 5) from post-capillary PH (Group 2) and help distinguish combined forms where both components are present. Blood tests, immunologic panels, liver ultrasound, HIV testing, and exercise capacity assessments fill in the clinical picture and narrow down the specific cause within a group.
The Updated Pressure Threshold
For decades, pulmonary hypertension was defined as a mean pulmonary artery pressure of 25 mmHg or higher. The 2022 ESC/ERS guidelines lowered this threshold to above 20 mmHg, reflecting evidence that pressures in the 21 to 24 mmHg range are already abnormal and carry prognostic significance. The previous cutoff of 25 mmHg was somewhat arbitrary, and data showed that patients with mildly elevated pressures already face increased risk.
Along with this change, the resistance threshold for pre-capillary pulmonary hypertension was adjusted from 3 Wood units down to greater than 2 Wood units. These shifts mean that some patients who would not have met the old definition now qualify for a pulmonary hypertension diagnosis, potentially allowing earlier identification and monitoring.