Pulmonary Hypertension Causes

In some cases, any underlying causes of pulmonary hypertension cannot be determined; this is called primary pulmonary hypertension or idiopathic pulmonary hypertension (idiopathic meaning “of unknown origin) . Up to ten percent of primary pulmonary hypertension cases are hereditary, that is, pulmonary hypertension occurs in more than one family member.

Another type of pulmonary hypertension, secondary pulmonary hypertension occurs as a result of other diseases or factors. Diseases associated with secondary pulmonary hypertension include chronic obstructive pulmonary disease (COPD), collagen vascular diseases like scleroderma, systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), congenital heart disease, ongoing liver disease, and human immunodeficiency virus (HIV). SPH is also associated with illicit drug use. Long-term exposure to high altitudes may also be responsible for some cases of secondary pulmonary hypertension.

Causes of Primary Pulmonary Hypertension

Primary pulmonary hypertension, or PPH, is a mysterious disease with no known cause. PPH appears at random and is difficult to study because it is so rare. Researchers believe genetics may contribute to its development. Primary pulmonary hypertension affects every age and ethnic group. Of the estimated three hundred cases of PPH diagnosed each year in the United States, the highest number of cases occurs in women between the ages of 21 and 40.

The first diagnosis of primary pulmonary hypertension was recorded in Germany in 1891. An autopsy revealed significant changes in the pulmonary arteries without any evidence of heart or lung disease.

In primary pulmonary hypertension, the top layer of cells within the pulmonary arterial walls (the endothelium) is injured or somehow changed. This alteration makes the muscles of the vessel grow and expand, leading to narrowing of the blood vessels. As the blood vessels get narrower, it becomes more difficult for blood to circulate through them. This creates a high pressure, which makes it necessary for the heart to work harder to circulate the blood. Without treatment, PPH can lead to heart failure.

Raynaud’s Disease

Research suggests that individuals who develop primary pulmonary hypertension may be sensitive to certain factors that damage the artery’s cells. A high correlation exists between a diagnosis of PPH and the presence of Raynaud’s disease. Raynaud’s disease affects the small blood vessels in the body causing inadequate blood flow; this results in an increased sensitivity to cold and may cause pain in the fingers and toes. Raynaud’s cannot be considered a cause of pulmonary hypertension since it is much more common than PPH, and many people with Raynaud’s never develop PPH.

The Genetic Link

Ongoing research points to potential genetic links as a cause of pulmonary hypertension. A genetic predisposition for PPH is linked to changes in a gene related to the bone morphogenetic protein (BMP) receptor II. The BMP has been identified in up to sixty percent of all hereditary primary pulmonary hypertensions. The BMP has also been identified in up to 25 percent of random cases of PPH. More studies are evaluating the genetic connection to PPH.

Causes of Secondary Pulmonary Hypertension

The most common type of pulmonary hypertension is known as secondary pulmonary hypertension (SPH or SPAH).

Diagram of Pulmonary CirculationBreathing Disorders: Secondary pulmonary hypertension is pulmonary hypertension that develops as a result of a primary disorder. Chronic bronchitis and emphysema, which are chronic obstructive pulmonary diseases (COPD), are common causes of secondary pulmonary hypertension. Interstitial lung disease and sleep apnea can also contribute to the development of SPH. Neonatal lung disease, a condition that can affect premature newborns whose lungs have not had a chance to develop completely, may contribute to pulmonary arterial hypertension. Pulmonary sarcoidosis, a chronic inflammation of the lung tissue that limits lung volume and makes the lungs “stiff” may also be a cause of pulmonary hypertension.

These respiratory diseases can prevent the transfer of adequate levels of oxygen from the lungs to the blood. Over time, as the blood vessels are deprived of oxygen, they begin to constrict. This chronic constriction can lead to pulmonary hypertension as well as congestive heart failure. Long exposures to high altitude can produce the same effect.

Blood Disorders: Other diseases such as sickle cell disease, pulmonary embolism, or blood clotting disorders can cause pulmonary hypertension. In these diseases vessels are blocked creating an increase in pressure in the pulmonary arteries and a lack of oxygenation to the blood.

Sclerosis: Systemic sclerosis, or scleroderma, is a disease that can scar the blood vessel walls. Sclerosis can affect the entire body (“systemic”) including the heart, lung, kidneys, skin, digestive tract, and extremities. People with sclerosis may experience decreased blood flow to the fingers and toes when they are cold (Raynaud’s disease), painful joints, heartburn, and difficulty swallowing.

Women are four times more likely than men to get systemic sclerosis. Up to fifteen percent of patients with systemic sclerosis develop pulmonary hypertension and PH is the main cause of mortality in patients with sclerosis.

Other Diseases: Patients suffering from complications due to human immunodeficiency virus (HIV) infection are at risk for secondary pulmonary hypertension. Portal hypertension, caused by an obstruction of flow to the venous system as a result of liver disease, can also result in PH.

Weight Loss Pills and Pulmonary Hypertension

Studies show a strong link between pulmonary hypertension and elevated serotonin levels. Serotonin levels are increased with weight loss pills containing the appetite suppressant drug dexfenfluramine-phentermine (“fen-phen”). Increased serotonin levels may result in sensitivity or injury to the blood vessels, a key component in the cause of pulmonary hypertension. As of September 1987, these drugs have been removed from the market.

Resources

American Lung Association. (November 2003). Primary pulmonary hypertension (PPH) fact sheet.

Fauci, A., Braunwald, E., Isselbacher, K., Wilson, J., Martin, J., Kasper, D., Hauser, S.