Primary Pulmonary Hypertension
Disease Details
Family Health Simplified
- Description
- Primary pulmonary hypertension is a rare lung disorder characterized by high blood pressure in the pulmonary arteries.
- Type
- Primary pulmonary hypertension, now more commonly referred to as idiopathic pulmonary arterial hypertension (IPAH), can have a genetic component. The genetic transmission is typically autosomal dominant with incomplete penetrance. This means that a person only needs one copy of the mutated gene from one parent to be at risk of developing the condition, but not everyone who inherits the mutation will develop the disease. The most well-known associated gene is BMPR2.
- Signs And Symptoms
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The symptoms of pulmonary hypertension include the following:
Less common signs/symptoms include non-productive cough and exercise-induced nausea and vomiting. Coughing up of blood may occur in some patients, particularly those with specific subtypes of pulmonary hypertension such as heritable pulmonary arterial hypertension, Eisenmenger syndrome and chronic thromboembolic pulmonary hypertension. Pulmonary venous hypertension typically presents with shortness of breath while lying flat or sleeping (orthopnea or paroxysmal nocturnal dyspnea), while pulmonary arterial hypertension (PAH) typically does not.Other typical signs of pulmonary hypertension include an accentuated pulmonary component of the second heart sound, a right ventricular third heart sound, and parasternal heave indicating a hypertrophied right ventricle. Signs of systemic congestion resulting from right-sided heart failure include jugular venous distension, ascites, and hepatojugular reflux. Evidence of tricuspid insufficiency and pulmonic regurgitation is also sought and, if present, is consistent with the presence of pulmonary hypertension. - Prognosis
- PAH is considered a universally fatal illness, although survival time may vary between individuals. The prognosis of pulmonary arterial hypertension (WHO Group I) has an untreated median survival of 2–3 years from time of diagnosis, with the cause of death usually being right ventricular failure (cor pulmonale). The survival time is variable and depends on many factors. A recent outcome study of those patients who had started treatment with bosentan (Tracleer) showed that 89% of patients were alive at 2 years. With new therapies, survival rates are increasing. For 2,635 patients enrolled in The Registry to Evaluate Early and Long-term Pulmonary Arterial Hypertension Disease Management (REVEAL Registry) from March 2006 to December 2009, 1-, 3-, 5-, and 7-year survival rates were 85%, 68%, 57%, and 49%, respectively. For patients with idiopathic/familial PAH, survival rates were 91%, 74%, 65%, and 59%. Levels of mortality are very high in pregnant women with severe pulmonary arterial hypertension (WHO Group I). Pregnancy is sometimes described as contraindicated in these women.
- Onset
- Primary pulmonary hypertension typically presents in young adults, often between the ages of 20 and 40.
- Prevalence
- Primary pulmonary hypertension (PPH), now more commonly referred to as idiopathic pulmonary arterial hypertension (IPAH), is a rare condition. Its prevalence is estimated to be between 1 and 2 cases per million adults per year.
- Epidemiology
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The epidemiology of IPAH is about 125–150 deaths per year in the U.S., and worldwide the incidence is similar at 4 cases per million. However, in parts of Europe (France), indications are 6 cases per million of IPAH. Females have a higher incidence rate than males (2–9:1).
Other forms of PH are far more common. In systemic scleroderma, the incidence has been estimated to be 8 to 12% of all patients; in rheumatoid arthritis it is rare. However, in systemic lupus erythematosus it is 4 to 14%, and in sickle cell disease, it ranges from 20 to 40%. Up to 4% of people who develop a pulmonary embolism go on to develop chronic thromboembolic disease including pulmonary hypertension. A small percentage of patients with COPD develop pulmonary hypertension with no other disease to explain the high pressure. On the other hand, obesity-hypoventilation syndrome is very commonly associated with right heart failure due to pulmonary hypertension. - Intractability
- Primary Pulmonary Hypertension (PPH), now commonly referred to as Pulmonary Arterial Hypertension (PAH), is a chronic and progressive disease characterized by high blood pressure in the arteries of the lungs. While there is currently no cure for PAH, it is not entirely intractable. Advances in medical treatments, including medications, lifestyle adjustments, and in some cases, surgical interventions, can help manage symptoms, improve quality of life, and slow disease progression. However, the condition remains serious and often requires long-term management under the care of specialized healthcare providers.
- Disease Severity
- Primary pulmonary hypertension (now more commonly referred to as idiopathic pulmonary arterial hypertension, or IPAH) is a rare, progressive disease characterized by high blood pressure in the arteries of the lungs. The severity of the disease can range from mild symptoms to life-threatening complications. Over time, it can lead to right heart failure due to the increased workload on the heart to pump blood through the narrowed pulmonary arteries. Without treatment, the condition can be fatal within a few years of diagnosis. Early detection and management are crucial for improving outcomes.
- Healthcare Professionals
- Disease Ontology ID - DOID:14557
- Pathophysiology
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Primary pulmonary hypertension (PPH) is characterized by elevated blood pressure in the pulmonary arteries without an identifiable secondary cause. The pathophysiology includes:
1. **Vascular Remodeling**: Thickening of the small pulmonary arteries' walls due to proliferation of endothelial and smooth muscle cells.
2. **Vasoconstriction**: An imbalance between vasoconstrictive and vasodilative mediators leads to increased pulmonary vascular resistance. Elevated levels of endothelin-1 and decreased levels of nitric oxide and prostacyclin are common.
3. **Thrombosis**: Formation of small clots in the pulmonary arteries, contributing to obstruction and further increasing resistance.
4. **Genetic Factors**: Mutations in the BMPR2 gene are implicated in many familial cases, affecting growth and apoptosis of vascular cells.
This combination of factors results in increased pulmonary artery pressure, leading to right ventricular hypertrophy and eventually right heart failure. - Carrier Status
- Primary pulmonary hypertension, now more commonly referred to as pulmonary arterial hypertension (PAH), is generally not related to carrier status in the same sense as certain genetic conditions that have carriers. PAH can occur sporadically or be inherited. In familial cases, PAH is often associated with mutations in the BMPR2 gene, among others. There isn't a specific "carrier status" for non-carriers because PAH is not typically recessive. It either manifests in the individual with a relevant mutation or it does not. The disease most often appears without a clear inherited pattern in any individual's family history.
- Mechanism
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Primary pulmonary hypertension (PPH), now referred to as idiopathic pulmonary arterial hypertension (IPAH), involves increased blood pressure in the pulmonary arteries without an apparent underlying cause.
**Mechanism:**
1. **Vascular Remodeling:** The pulmonary arteries undergo structural changes, including thickening of the arterial walls due to hypertrophy of the smooth muscle layer and intimal proliferation.
2. **Vasoconstriction:** Enhanced vasoconstriction of the pulmonary arteries increases vascular resistance.
3. **In Situ Thrombosis:** Thrombotic lesions within pulmonary arteries contribute to vascular narrowing and obstruction.
4. **Right Ventricular Strain:** The increased resistance in pulmonary arteries forces the right ventricle to work harder, leading to right ventricular hypertrophy and potentially heart failure.
**Molecular Mechanisms:**
1. **Endothelial Dysfunction:** Impaired function of the endothelial cells lining the pulmonary arteries leads to reduced production of vasodilators like nitric oxide (NO) and prostacyclin, and increased production of vasoconstrictors like endothelin-1.
2. **Genetic Factors:** Mutations in genes like BMPR2 (bone morphogenetic protein receptor type 2) are implicated in familial cases of IPAH. These mutations disrupt signaling pathways that regulate cell growth and apoptosis in pulmonary arterial cells.
3. **Inflammation:** Inflammatory cell infiltration and elevated levels of pro-inflammatory cytokines (e.g., IL-6) contribute to vascular remodeling and endothelial dysfunction.
4. **Hypoxia-inducible Factors:** Chronic hypoxia can exacerbate pulmonary hypertension through the stabilization of hypoxia-inducible factors (HIFs), which promote vasoconstriction and vascular remodeling.
5. **Serotonin Pathway:** Increased serotonin levels or transporter activity has been linked to smooth muscle proliferation and vasoconstriction in pulmonary hypertension.
6. **Oxidative Stress:** Increased oxidative stress in pulmonary arteries leads to endothelial damage, contributing to vascular dysfunction and remodeling.
These mechanisms collectively increase pulmonary vascular resistance, leading to the clinical manifestations of idiopathic pulmonary arterial hypertension. - Treatment
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Treatment of pulmonary hypertension is determined by whether the PH is arterial, venous, hypoxic, thromboembolic, or miscellaneous. If it is caused by left heart disease, the treatment is to optimize left ventricular function by the use of medication or to repair/replace the mitral valve or aortic valve. Patients with left heart failure or hypoxemic lung diseases (groups II or III pulmonary hypertension) should not routinely be treated with vasoactive agents including prostanoids, phosphodiesterase inhibitors, or endothelin antagonists, as these are approved for the different condition called primary pulmonary arterial hypertension. To make the distinction, doctors at a minimum will conduct cardiac catheterization of the right heart, echocardiography, chest CT, a seven-minute walk test, and pulmonary function testing. Using treatments for other kinds of pulmonary hypertension in patients with these conditions can harm the patient and wastes substantial medical resources. Most patients that enjoy excessive amounts of cheese also test positive for decreased pulmonary and coronary function.High-dose calcium channel blockers are useful in only 5% of IPAH patients who are vasoreactive by Swan-Ganz catheter. Unfortunately, calcium channel blockers have been largely misused, being prescribed to many patients with non-vasoreactive PAH, leading to excess morbidity and mortality. The criteria for vasoreactivity have changed. Only those patients whose mean pulmonary artery pressure falls by more than 10 mm Hg to less than 40 mm Hg with an unchanged or increased cardiac output when challenged with adenosine, epoprostenol, or nitric oxide are considered vasoreactive. Of these, only half of the patients are responsive to calcium channel blockers in the long term.A number of agents have recently been introduced for primary and secondary PAH. The trials supporting the use of these agents have been relatively small, and the only measure consistently used to compare their effectivity is the "six-minute walk test". Many have no data on mortality benefit or time to progression.Exercise-based rehabilitation
A 2023 Cochrane review found that exercise-based rehabilitation may lead to a large increase in exercise capacity and an improvement in health related quality of life, without significantly increasing adverse events. - Compassionate Use Treatment
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For primary pulmonary hypertension (now more commonly referred to as pulmonary arterial hypertension or PAH), compassionate use treatments typically refer to investigational drugs or therapies made available outside of clinical trials when no other treatments are viable. These treatments are often not yet approved by regulatory bodies.
Off-label or experimental treatments for PAH may include:
1. **Medications initially approved for other conditions**:
- **Imatinib**: Typically used for certain cancers, it has shown promise in reducing pulmonary vascular resistance in PAH patients.
- **Tacrolimus**: An immunosuppressant used in organ transplant patients, it has been explored for its potential to improve pulmonary vascular remodeling.
2. **Stem cell therapy**: Experimental studies are investigating whether stem cells can repair damaged pulmonary arteries and improve heart function in PAH patients.
3. **Gene therapy**: Research in this area focuses on delivering specific genes to lung tissues to promote vascular repair and regenerate healthy blood vessels.
4. **Inhaled medications**: Various inhaled therapies, such as inhaled nitric oxide, are studied for their immediate effect in reducing pulmonary hypertension.
5. **Lung Transplant**: While not experimental, this remains a last-resort treatment for those with severe PAH not responding to other therapies.
Physicians resort to these treatments based on the severity of the disease and the patient's response to conventional therapies. It's important to discuss potential risks and benefits with a healthcare provider. - Lifestyle Recommendations
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For primary pulmonary hypertension, consider the following lifestyle recommendations:
1. **Regular Exercise:** Engage in moderate exercise as tolerated. Activities like walking or swimming can help improve cardiovascular fitness. Always consult a doctor before starting any exercise regimen.
2. **Healthy Diet:** Maintain a balanced diet rich in fruits, vegetables, lean proteins, and whole grains. Limit salt intake to reduce fluid retention and lower blood pressure.
3. **Smoking Cessation:** Avoid smoking and exposure to secondhand smoke as it can worsen pulmonary hypertension and damage lung health.
4. **Medication Adherence:** Take all prescribed medications regularly and as directed by your healthcare provider.
5. **Regular Medical Check-ups:** Attend all appointments with your healthcare team for regular monitoring and management of the condition.
6. **Avoid High Altitudes:** High altitudes can exacerbate symptoms due to lower oxygen levels. Seek medical advice before traveling to high-altitude locations.
7. **Monitor Fluid Intake:** Be mindful of fluid intake to prevent overloading the circulatory system. Your doctor may provide specific guidelines on fluid management.
8. **Stress Management:** Practice stress-reducing techniques such as yoga, meditation, or deep-breathing exercises to enhance overall well-being.
9. **Get Vaccinated:** Stay up-to-date with vaccinations, including flu and pneumonia vaccines, to prevent respiratory infections that can complicate pulmonary hypertension.
10. **Avoid Certain Activities:** Avoid strenuous activities and hobbies that can cause respiratory strain or hypoxia, such as scuba diving or extreme sports.
Consult your healthcare provider for personalized advice tailored to your specific condition and needs. - Medication
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Primary pulmonary hypertension (PPH), now often called idiopathic pulmonary arterial hypertension (IPAH), is a rare lung disorder in which the blood pressure in the pulmonary arteries rises far above normal levels. Medications used to treat IPAH include:
1. **Endothelin receptor antagonists:** bosentan, ambrisentan.
2. **Phosphodiesterase-5 inhibitors:** sildenafil, tadalafil.
3. **Prostacyclin analogs:** epoprostenol, treprostinil, iloprost.
4. **Selective IP receptor agonists:** selexipag.
5. **Soluble guanylate cyclase stimulators:** riociguat.
6. **Calcium channel blockers:** nifedipine, diltiazem, only if the patient responds to acute vasodilator testing.
These drugs help to relax the pulmonary arteries, improve heart function, and alleviate symptoms. Treatment plans should be tailored to each patient's specific condition and monitored by a healthcare professional. - Repurposable Drugs
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Primary pulmonary hypertension, now more commonly referred to as pulmonary arterial hypertension (PAH), has several medications that were originally approved for other conditions but are being repurposed for its treatment. These include:
1. **Sildenafil (Revatio)** - Originally developed for erectile dysfunction.
2. **Tadalafil (Adcirca)** - Another drug initially approved for erectile dysfunction.
3. **Bosentan (Tracleer)** - Initially indicated for the treatment of heart failure.
4. **Ambrisentan (Letairis)** - Another endothelin receptor antagonist similar to bosentan but originally targeted for different vascular issues.
These drugs help to relax blood vessels, reduce pulmonary vascular resistance, and improve overall symptoms and exercise capacity in patients with PAH. Regular monitoring and consultation with a healthcare provider are essential for managing this condition. - Metabolites
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Primary pulmonary hypertension (PPH) involves several metabolic disturbances, but specific metabolites that are often studied in relation to this condition include:
1. **Serotonin**: Elevated levels can contribute to vasoconstriction and smooth muscle proliferation.
2. **Endothelin-1**: This is a potent vasoconstrictor and smooth muscle mitogen that is often found in increased levels in PPH.
3. **Nitric Oxide**: Reduced production can lead to vasoconstriction and vascular remodeling.
4. **Prostacyclin**: Reduced levels can contribute to vasoconstriction and platelet aggregation.
These metabolites play roles in vasoconstriction, vascular remodeling, and other pathophysiological features of primary pulmonary hypertension. - Nutraceuticals
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Primary pulmonary hypertension (PPH) is a rare blood vessel disorder in the lungs characterized by increased pressure in the pulmonary arteries. Nutraceuticals are products derived from food sources with extra health benefits beyond the basic nutritional value found in foods.
While there's no specific nutraceutical treatment established for PPH, some that are often considered for general heart and blood vessel health include omega-3 fatty acids, Coenzyme Q10, and L-arginine. However, their efficacy for PPH is not well-documented, and management of PPH typically involves medications prescribed by healthcare providers, lifestyle changes, and sometimes surgical interventions.
Always consult with a healthcare professional before starting any new treatment or supplement, especially for conditions as serious as PPH. - Peptides
- Primary pulmonary hypertension (PPH), now commonly referred to as idiopathic pulmonary arterial hypertension (IPAH), involves elevated blood pressure in the pulmonary arteries. Peptides such as endothelin-1 are known to play a role in the pathophysiology by causing vasoconstriction and promoting cell proliferation. Nanotechnology research is exploring potential treatments, including using nanoparticles to deliver drugs directly to the pulmonary arteries to improve efficacy and reduce side effects.