What causes pulmonary hypertension?

From the Guidelines

Pulmonary hypertension is a complex condition caused by various factors, including left heart disease, lung disease, and thromboembolic disease. Certain medications and conditions, such as scleroderma, sickle cell disease, and HIV infection, can also contribute to its development, often due to chronic inflammation, vascular remodeling, and endothelial dysfunction 1.

Causes of Pulmonary Hypertension

• Left heart disease: Left ventricular systolic dysfunction, left ventricular diastolic dysfunction, valvular disease, and congenital or acquired left heart inflow/outflow tract obstruction and congenital cardiomyopathies 1
• Lung disease: Chronic obstructive pulmonary disease, interstitial lung disease, other pulmonary diseases with mixed restrictive and obstructive pattern, sleep-disordered breathing, alveolar hypoventilation disorders, and chronic exposure to high altitude 1
• Thromboembolic disease: Chronic thromboembolic pulmonary hypertension and other pulmonary artery obstructions, such as angiosarcoma, other intravascular tumors, arteritis, congenital pulmonary arteries stenoses, and parasites (hydatidosis) 1
• Other conditions: Connective tissue disease, portal hypertension, congenital heart disease, schistosomiasis, and human immunodeficiency virus infection 1

Clinical Classification of Pulmonary Hypertension

The clinical classification of pulmonary hypertension includes five groups:

• Group 1: Pulmonary arterial hypertension (PAH)
• Group 2: Pulmonary hypertension due to left heart disease
• Group 3: Pulmonary hypertension due to lung diseases and/or hypoxia
• Group 4: Chronic thromboembolic pulmonary hypertension and other pulmonary artery obstructions
• Group 5: Pulmonary hypertension with unclear and/or multifactorial mechanisms 1

From the Research

Causes of Pulmonary Hypertension

Pulmonary hypertension is a complex disease with multiple causes, including:

• Pulmonary arterial hypertension (rare) 2
• Pulmonary hypertension associated with left-sided heart disease (very common) 2, 3
• Pulmonary hypertension associated with lung disease (common) 2
• Pulmonary hypertension associated with pulmonary artery obstructions, usually related to thromboembolic disease (rare) 2
• Pulmonary hypertension with unclear and/or multifactorial mechanisms (rare) 2

Pathophysiology

The pathophysiology of pulmonary hypertension involves:

• Vascular remodeling and obliteration of the precapillary pulmonary arterioles 4
• Endothelial dysfunction, leading to the activation of cellular signaling pathways and uncontrolled proliferation of endothelial cells, pulmonary artery smooth muscle cells, and fibroblasts 5
• Inflammation, with infiltration of immune cells into the vascular wall and increased levels of cytokines and chemokines 4, 6
• Pulmonary arterial stiffening, contributing to vascular remodeling and disease progression 6

Key Factors

Key factors contributing to the development and progression of pulmonary hypertension include:

• Altered immune and vascular cells 4
• Endothelial to mesenchymal transition, inflammation, apoptosis, and thrombus formation 5
• Vascular calcification, smooth muscle cell stiffening, vascular wall thickening, and tissue fibrosis 6