This comprehensive Nature Reviews Disease Primers paper provides an authoritative overview of pulmonary hypertension (PH) globally, with particular attention to disparities between high-income (HICs) and low- and middle-income countries (LMICs).
Key Points
Classification and Prevalence: pulmonary hypertension is defined as mean pulmonary artery pressure >20 mmHg and comprises five groups: Group 1 (pulmonary arterial hypertension/PAH – rare), Group 2 (left-sided heart disease – very common), Group 3 (lung disease – common), Group 4 (pulmonary artery obstructions/chronic thromboembolic CTEPH – rare), and Group 5 (unclear/multifactorial mechanisms – rare). At least 1% of the global population is affected, with higher burdens likely in low- and middle-income countries (LMICs)
Geographic Variations: The disease profile differs dramatically by region. In high-income countries, pulmonary hypertension with left heart disease dominates, driven by coronary disease, obesity, and heart failure. In low- and middle-income countries right heart disease, cardiomyopathies, HIV, schistosomiasis, tuberculosis, congenital heart disease, and indoor air pollution are major contributors. Schistosomiasis is a leading pulmonary arterial hypertension cause in South America and Africa.
Pathophysiology: All pulmonary hypertension forms share common pathways involving pulmonary vascular remodeling, leading to right ventricular hypertrophy and eventual failure. Key mechanisms in pulmonary arterial hypertension include endothelial dysfunction, mitochondrial metabolic abnormalities (Warburg metabolism), epigenetic dysregulation, inflammation, ion channel dysfunction, and impaired calcium homeostasis. Genetic mutations (particularly BMPR2) account for ~70% of familial pulmonary arterial hypertension cases.
Diagnosis Challenges: Diagnosis requires right heart catheterization (gold standard), but access is severely limited in low- and middle-income countries. Echocardiography serves as the primary screening tool globally. Diagnostic delays of 2-3 years are common even in high-income settings, contributing to poor outcomes.
Treatment: Evidence-based pulmonary arterial hypertension therapies (targeting prostacyclin, nitric oxide, and endothelin pathways) have transformed outcomes for Groups 1 and 4. However, these expensive medications are largely inaccessible in low- and middle-income countries. For Groups 2 and 3 (the most common forms globally), treatment focuses on managing underlying conditions, with limited pulmonary arterial hypertension-specific therapy options.
Prognosis: Even mild pulmonary hypertension significantly increases mortality risk. Survival depends on pulmonary hypertension subtype, age, disease severity, and treatment access. The disease disproportionately affects younger individuals in llow- and middle-income countries due to preventable causes.
Quality of life: Pulmonary hypertension profoundly impacts physical functioning, mental health, and survival. Diagnostic delays and limited treatment access (especially in low- and middle-income countries) mean many patients suffer prolonged disability before receiving appropriate care.
Conclusions: This paper provides essential background knowledge because it: (1) Highlights that pulmonary hypertension is not a rare disease globally – Groups 2 and 3 affect far more people than the well-studied Group 1 pulmonary arterial hypertension; (2) Documents stark geographic inequalities in causes, diagnosis, and treatment access; (3) Emphasizes that conditions like schistosomiasis, Tuberculosis, HIV, and Right Heart Disease drive substantial pulmonary hypertension burden in resource-limited settings; (4) Reveals major knowledge gaps – most research focuses on pulmonary arterial hypertension in high income countries, while the pathophysiology and optimal treatments for common pulmonary hypertension forms in low to medium income countries remain understudied; (5) Calls for urgent action on prevention, early detection, equitable access to diagnostics and treatments, and research that includes diverse populations globally.
Sections
- Introduction
- Epidemiology
- Pathophysiology
- Diagnosis, screening and
- prevention
- Management
- Quality of life
- Outlook
Citation
Mocumbi, A., Humbert, M., Saxena, A. et al. Pulmonary hypertension. Nat Rev Dis Primers 10, 1 (2024). https://doi.org/10.1038/s41572-023-00486-7, Accepted 27 November 2023, Published 04 January 2024, Version of record, 04 January 2024,
Read more at this link on Nature Reviews Disease Primers