The most common cause of pulmonary hypertension is left heart failure leading to pulmonary venous hypertension (WHO Group II). This may be due to systolic or diastolic malfunction of the left ventricle or due to valvular dysfunction such as mitral regurgitation, mitral stenosis, aortic stenosis, or aortic regurgitation. It usually manifests as pulmonary edema or pleural effusions. Because the malfunctioning heart does not pump efficiently, blood fails to leave the pulmonary circulation in a timely manner, leading to abnormally high pressure in the pulmonary veins.[2] The increased pressure in the pulmonary veins can be transmitted back to the pulmonary arteries.[2]
Common causes of pulmonary arterial hypertension (PAH, WHO Group I) include HIV, scleroderma and other autoimmune disorders, cirrhosis and portal hypertension, sickle cell disease,[3] congenital heart disease, and others. Use of weight loss pills such as Fen-Phen, Aminorex, fenfluramine (Pondimin), and phentermine led to the development of PAH in the past.[4] These drugs were withdrawn from the market when the link between their use and greater incidence of PAH was established.
Human herpesvirus 8, also associated with Kaposi's sarcoma, has been demonstrated in patients with PAH, suggesting that this virus may play a role in its development.[5] Recent studies have been unable to find an association between human herpesvirus 8 and idiopathic pulmonary arterial hypertension.
When a family history exists, the disease is termed familial pulmonary arterial hypertension (FPAH). IPAH and FPAH are now considered to be genetic disorders linked to mutations in the BMPR2 gene, which encodes a receptor for bone morphogenetic proteins,[6] as well as the 5-HT(2B) gene, which codes for a serotonin receptor.[7]. There seems to be an association of idiopathic PAH (not only PAH caused by heart malformations) and Trisomy 21.
Pulmonary embolism also leads to pulmonary hypertension, acutely as well as chronically (WHO Group IV). Treatments for these two conditions are vastly different. Schistosomiasis is a very common cause of pulmonary hypertension in endemic areas such as the Nile river due to obstruction of pulmonary vessels with the parasite.
Lung diseases that lower oxygen in the blood (hypoxia) are well known causes of pulmonary hypertension (WHO Group III), including COPD, interstitial lung disease such as IPF, Pickwickian syndrome or obesity-hypoventilation syndrome, and possibly sleep apnea.
Other causes include sarcoidosis, histiocytosis X, and fibrosing mediastinitis (WHO Group V).
When none of these causes can be found, the disease is termed idiopathic pulmonary arterial hypertension (IPAH). There appears to be a link between IPAH and thyroid diseases,[8] but this is not regarded as causative.
