Pulmonary hypertension develops when the blood vessels in your lungs become narrowed, stiffened, or blocked, forcing your heart to pump harder to push blood through them. It’s diagnosed when the average pressure in the pulmonary arteries rises above 20 mmHg at rest, measured by a catheter placed in the right side of the heart. There isn’t one single cause. The condition has at least five distinct categories of triggers, ranging from heart failure to chronic lung disease to genetics.
Left Heart Disease Is the Most Common Cause
The single biggest driver of pulmonary hypertension is a problem on the left side of the heart. In a large population study from Ontario, Canada, left heart disease accounted for over 75% of all new pulmonary hypertension cases. When the left side of your heart can’t pump efficiently, or when a heart valve leaks or narrows, blood backs up into the lungs. That backup raises pressure in the pulmonary arteries over time.
This can happen with heart failure (whether the heart muscle is too weak or too stiff), diseased heart valves, or long-standing high blood pressure throughout the body. Many people who develop this form of pulmonary hypertension already know they have a heart condition. The pulmonary hypertension is a downstream consequence, not the original problem.
Chronic Lung Disease and Low Oxygen
The second most common category involves lung conditions that reduce your body’s oxygen supply. COPD, pulmonary fibrosis, sleep apnea, and even long-term exposure to high altitude can all trigger it. In the Ontario study, lung-related pulmonary hypertension was present in 47% of the overall pulmonary hypertension population, often overlapping with left heart disease.
Low oxygen is the central driver here. When oxygen levels drop, the blood vessels in your lungs reflexively tighten to redirect blood toward healthier lung tissue. That’s a useful short-term response. But when the low oxygen is chronic, the vessels stay constricted, and their walls begin to physically remodel, becoming thicker and stiffer. Inflammation from the underlying lung disease accelerates this process, and in some cases the lung tissue itself is destroyed, reducing the number of vessels available for blood to flow through.
What Happens Inside the Blood Vessels
Regardless of the initial trigger, pulmonary hypertension shares a common feature: the walls of the pulmonary arteries change in ways that make them narrower and less flexible. This process, called vascular remodeling, involves all three layers of the artery wall. The inner lining (endothelium) stops functioning properly. The muscle layer in the middle thickens as smooth muscle cells multiply and migrate. The outer layer stiffens as connective tissue cells become more active.
In a healthy lung, the inner lining of the arteries releases chemicals that keep vessels relaxed and open. Two of the most important are nitric oxide and prostacyclin, both of which dilate blood vessels and prevent the muscle layer from growing too thick. In pulmonary hypertension, levels of both are reduced. At the same time, levels of a powerful vessel-constricting chemical called endothelin-1 are elevated. This imbalance, less relaxation and more constriction, drives the progressive narrowing that defines the disease.
Blood Clots That Never Fully Dissolve
A distinct form called chronic thromboembolic pulmonary hypertension (CTEPH) develops only in people who have had blood clots travel to their lungs. Normally, the body breaks down these clots over time. In CTEPH, the clots don’t fully dissolve. Instead, they organize into scar-like tissue that narrows or blocks the affected vessels. The more vessels are compromised, the higher the pressure climbs. This form represented about 9% of pulmonary hypertension cases in the Ontario cohort.
Not everyone who has a pulmonary embolism goes on to develop CTEPH. But it’s an important cause to identify because, unlike many other forms of pulmonary hypertension, it can sometimes be treated with surgery to remove the scar tissue.
Genetic Causes and Inherited Risk
Some people develop pulmonary arterial hypertension, the rarer form that originates in the lung vessels themselves, because of a genetic mutation. The most well-known is a mutation in the BMPR2 gene, which provides instructions for a receptor involved in controlling cell growth in blood vessel walls. When this gene is faulty, the signaling that normally keeps vessel walls from thickening breaks down.
Over 300 different BMPR2 mutations have been identified. Among families with a known history of pulmonary arterial hypertension, about 82% carry a BMPR2 mutation. Among people diagnosed with no family history, about 17% still turn out to carry one. Having the mutation doesn’t guarantee you’ll develop the disease. Penetrance is only 20 to 30%, meaning most carriers never become symptomatic. But the risk is significant enough that genetic counseling and screening are recommended for close relatives of affected patients.
Drugs, Toxins, and Diet Pills
Certain substances can directly damage the pulmonary blood vessels and trigger pulmonary arterial hypertension. Methamphetamines are the most clearly established drug cause. The link between stimulants and pulmonary hypertension was first recognized in the 1960s when an amphetamine-like appetite suppressant called aminorex caused a spike in cases across Europe. Later, the diet drugs fenfluramine and dexfenfluramine (often combined with phentermine in the “fen-phen” combination) were linked to the same problem. Cocaine and other amphetamines are also considered possible triggers.
These drugs appear to cause the same kind of vascular remodeling seen in other forms of the disease. The risk generally increases with longer use, though individual susceptibility varies, likely influenced by underlying genetic factors.
Autoimmune and Connective Tissue Diseases
Autoimmune conditions that affect connective tissue carry a meaningful risk of pulmonary hypertension. Scleroderma (systemic sclerosis) is the most strongly associated. Estimates based on right heart catheterization, the gold standard measurement, put the prevalence of pulmonary hypertension in scleroderma patients between 7% and 29%. The wide range reflects differences in how aggressively patients are screened. Lupus also carries risk, though prevalence estimates are lower and more variable, ranging from less than 1% up to 14%.
In these conditions, the immune system’s chronic inflammatory attack on blood vessel tissue drives the same endothelial damage and vascular remodeling that characterizes other forms. Patients with scleroderma or lupus are typically screened with echocardiograms at regular intervals because catching pulmonary hypertension early changes treatment options.
Other Less Common Triggers
A final group of causes doesn’t fit neatly into any of the above categories. These include blood disorders like sickle cell disease and other forms of chronic hemolytic anemia, where ongoing red blood cell destruction releases substances that damage blood vessel linings. Metabolic conditions such as thyroid disorders and certain rare storage diseases can also contribute. Sarcoidosis, a condition causing inflammatory clumps in organs including the lungs, is another recognized cause. HIV infection and chronic liver disease with portal hypertension round out the list. In many of these conditions, multiple mechanisms overlap, making the exact pathway harder to pin down.
Congenital heart defects are worth noting separately. Defects that allow blood to flow abnormally between the left and right sides of the heart can send too much blood into the pulmonary arteries, gradually raising pressure and damaging the vessels. This can develop in childhood or not become apparent until adulthood, depending on the size and type of defect.