Pulmonary hypertension is a complex progressive disorder characterized by elevated pulmonary artery pressure. Diagnosis requires early clinical suspicion based on symptoms such as exertional dyspnea, fatigue, syncope, and chest discomfort, with echocardiography as a first-line diagnostic study. Diagnosis is confirmed using right heart catheterization, with a mean pulmonary artery pressure of 20 mm Hg or more and pulmonary vascular resistance greater than 2 Wood units. Strategies for primary and secondary prevention include regular physical activity, tobacco cessation, weight management, immunizations, and family planning to minimize risks associated with pregnancy. Prevention and evidence-based control of hypertension, diabetes, and dyslipidemia are essential. Occupational and environmental exposures, including poor indoor and outdoor air quality, should be addressed. Advances in pharmacotherapy for pulmonary arterial hypertension that target the endothelin, prostacyclin, and nitric oxide pathways and activin receptor inhibition have improved outcomes. Endothelin receptor antagonists, prostacyclin analogues, and phosphodiesterase 5 inhibitors are key treatment options. Combination therapy is recommended for patients with moderate to severe disease, whereas parenteral prostanoids are indicated for advanced pulmonary arterial hypertension. Right-sided heart failure, a major complication, is managed with fluid management and diuretics, with lung transplant evaluation and palliative shunt procedures considered for refractory cases. Addressing nutrition and iron deficiency are important supportive measures.

Case 1. AC is a 54-year-old patient with exertional dyspnea, fatigue, and lower extremity edema that has progressed over the past 6 months. She has obstructive sleep apnea but uses her continuous positive airway pressure machine inconsistently. Her lungs are clear on auscultation. Computed tomography angiography of the chest, performed during a recent emergency department visit, showed no pulmonary embolism. Echocardiography shows right ventricular hypertrophy, moderate tricuspid regurgitation with an elevated jet velocity of 3.5 m/s (less than 2.9 m/s is normal), and findings suggestive of increased pulmonary artery pressure.

Pulmonary hypertension is defined as an increased mean pulmonary artery pressure (MPAP) of 20 mm Hg or more as measured with resting right heart catheterization.1 Clinicians should suspect pulmonary hypertension in patients with symptoms of exertional dyspnea, progressive fatigue, syncope, pedal edema, or symptoms and signs of left-sided heart disease. Hypoxia at rest or during exertion may also be present.1,2

Pulmonary hypertension is a progressive condition that, if untreated, leads to increased pulmonary vascular resistance (PVR), right ventricular dysfunction, and eventually right-sided heart failure. Increased PVR (often a five- to 10-fold increase) leads to right ventricular hypertrophy and dilatation, which can result in premature death and disability.14 Right ventricular function is the primary determinant of prognosis and survival.1

Epidemiology

Pulmonary hypertension affects approximately 1% of the global population and up to 1 in 10 people 65 years and older.3 Pulmonary hypertension was classified into five etiologic groups during the 2018 World Symposium on Pulmonary Hypertension2 (Table 11,2,5).

Table 1 Classifications of Pulmonary Hypertension

SubcategoriesClinical featuresEchocardiography findingsRight heart catheterization findings
Group 1: pulmonary arterial hypertension
Associated with connective tissue diseases, HIV, portal hypertension, or schistosomiasis

Drug- or toxin-induced

Heritable

Idiopathic
Symptoms/signs of exertional dyspnea, syncope, elevated jugular venous pressure, pedal edema

Variable age at onset; relatively younger age (younger than 50 years) and female predominance
Signs of pulmonary hypertension (increased systolic PAP, hypertrophic or enlarged right atrium/ventricle); findings of congenital heart defectsPrecapillary pulmonary hypertension (mean PAP > 20 mm Hg, pulmonary arterial wedge pressure ≤ 15 mm Hg, PVR ≥ 3 WU)
Group 2: pulmonary hypertension associated with left-sided heart disease
Heart failure with preserved or reduced ejection fraction

Postcapillary pulmonary hypertension secondary to congenital or acquired cardiovascular disease

Valvular heart disease
Symptoms/signs of left-sided or valvular heart disease (dyspnea, fatigue, orthopnea, leg edema)

Most common in older women who have heart failure with preserved ejection fraction and older men who have heart failure with reduced ejection fraction
Signs of left-sided heart disease and pulmonary hypertension (reduced [≤ 40%] or mildly reduced [41%-49%] left ventricular ejection fraction, increased systolic PAP, enlarged right atrium/ventricle)Isolated postcapillary pulmonary hypertension (mean PAP > 20 mm Hg, pulmonary arterial wedge pressure > 15 mm Hg, PVR < 3 WU)

Combined pre- and postcapillary pulmonary hypertension (mean PAP > 20 mm Hg, pulmonary arterial wedge pressure > 15 mm Hg, PVR ≥ 3 WU)
Group 3: pulmonary hypertension associated with lung disease, hypoxia, or both
Developmental lung disorder

Obstructive and/or restrictive lung disease
Chronic hypoxia at rest or during exertion

Abnormal findings on pulmonary function testing, chest imaging, and polysomnography
Signs of pulmonary hypertension (increased systolic PAP, enlarged right atrium/ventricle)Precapillary pulmonary hypertension unless associated with coexisting condition (eg, left-sided heart disease)
Group 4: pulmonary hypertension associated with pulmonary artery obstruction
Chronic thromboembolic pulmonary hypertension

Malignant tumors

Other pulmonary artery obstructions (eg, benign tumors, arteritis without connective tissue disease, congenital artery stenosis, parasitic infections such as hydatidosis)
Symptoms/signs of pulmonary hypertension (see Group 1)

Abnormal findings on ventilation perfusion scan, computed tomography angiography, or both
Signs of pulmonary hypertension (increased systolic PAP, enlarged right atrium/ventricle)Precapillary pulmonary hypertension unless associated with coexisting condition (eg, left-sided heart disease)
Group 5: pulmonary hypertension with multifactorial or unclear mechanisms
Complex congenital heart disease

Hematologic disorders

Systemic and metabolic disorders (eg, Gaucher disease, glycogen storage disease, neurofibromatosis, sarcoidosis, chronic kidney failure with or without hemodialysis)
Symptoms/signs of the underlying condition (eg, anemia, metabolic dysfunction)Varies by etiologyPrecapillary pulmonary hypertension (eg, hemoglobinopathies, myeloproliferative disease)

Isolated postcapillary or combined pre- and postcapillary pulmonary hypertension

PAP = pulmonary artery pressure; PVR = pulmonary vascular resistance; WU = Wood units.

Information from references 1, 2, and 5.

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