The presentation of pulmonary arterial hypertension (PAH) has varied in patients of different ethnic and racial groups. A nascent research effort is underway to detect more of these PAH underpinnings to guide clinicians in tailoring treatment for this rare and often fatal disease. Estimates of PAH prevalence range from 5.9 to 60 cases per million, with a 1-year mortality rate of more than10% for patients with poor functional status and right heart failure.1
Research in related fields has demonstrated that therapy based on race and ethnicity might provide more targeted treatment, such as first-line therapies for blacks with hypertension.2 In PAH, structural and functional differences in right ventricle abnormalities may guide clinicians to use individualized treatments based on patients’ genetics.2
To get a snapshot of the current landscape of how ethnicity and race may influence PAH treatment, Pulmonology Advisor spoke with several pulmonologists: Vinicio de Jesus Perez, MD, assistant professor of medicine at Stanford University School of Medicine in Stanford, California; Nicholas S. Hill, MD, chief of the pulmonary, critical care and sleep division and professor at Tufts University School of Medicine in Boston, Massachusetts; and Victor J. Test, MD, professor of medicine at Duke University School of Medicine in Durham, North Carolina.
Pulmonology Advisor: What characteristics are distinct from one ethnic group or race to another in PAH?
Dr de Jesus Perez: We do not have anything now that tells us how to approach the diagnosis of PAH in different racial or ethnic groups. When I became interested in this topic 2 years ago, I could find no more than 5 papers on the subject, yet for cancer and stroke, we have a wealth of literature noting the disparities in minority health in terms of quality of care and costs, but not for PAH.
Dr Test: PAH is a syndrome, which means that it is caused by many different things. There are clear ethnic differences in its causes.
In idiopathic PAH, formerly known as primary pulmonary hypertension, whites predominate while blacks have a heavier burden of PAH associated with connective tissue disorders such as lupus and scleroderma. In a recent publication of a national registry, Hispanic patients with PAH are more likely to have congenital heart disease.3
Ethnicity plays a significant role in other types of PAH as well. Blacks have a higher burden of systemic essential hypertension and thus may have a higher incidence of renal failure and hypertensive heart disease, which predisposes them to PAH associated with left heart disease. In addition, sickle cell anemia and sarcoidosis are associated with a complex form of PAH. These conditions are more common in blacks.
Pulmonology Advisor: How does this affect treatment for individuals with PAH?
Dr de Jesus Perez: We need to realize that we are dealing with a unique population and that we need to start treatment early, especially with prostanoids.1,4,5
Dr Hill: We do not know enough about ethnic or racial differences in PAH to have any rationale for treating patients differently. Some recent large studies have not even reported race or ethnicity.
Dr Test: The etiology of PAH dictates the types of therapies that are chosen. In a recent publication, Hispanic patients received PAH therapy less often than either whites or blacks.3 The reasons for this are unclear. It is [also] not clear how socioeconomic factors such as access to health care and insurance affect this rate from the available information.
Pulmonology Advisor: Where should we focus future research efforts?
Dr de Jesus Perez: We need to learn everything about how PAH manifests in racial and ethnic minorities, but if I were to prioritize one aspect, it would be the management of PAH.
The soon-to-be published American Thoracic Society research statement [on racial and ethnic disparities in PAH] is a call to arms. We need to understand the genetic factors of PAH. We also need a better understanding of the following aspects about PAH management:
- Concerns unique to minorities
- How socioeconomic status affects quality of life for patients with PAH
- Attitudes of patients from diverse backgrounds seeing clinicians and the attitude of clinicians toward minority patients (language and cultural barriers)
- Environmental role (pollution, violence, drugs) in PAH
- Health policy toward minorities with PAH
By studying registry data, specifically tissue banks for blood samples, we will know how patients respond to various treatments and generally how genetics and socioeconomic status affect health outcomes in patients with PAH.
Dr Hill: Future studies and registries need to consider race and ethnicity to know whether [they] really do make a difference.
Dr Test: Research should focus on additional therapies for PAH that would enable a more tailored treatment approach for individual patients. [There needs to be] research and evaluation into the delay of diagnosis that is pervasive in all patients with PAH. Identifying the barriers to diagnosis and access to care is essential for all patients.
We do need outcome studies that more closely evaluate the ethnic and socioeconomic factors that affect treatment outcomes. Until recently, PAH trials have not been multinational, so the trials tended to reflect the ethnic makeup of a particular nation. As the trials become multinational, there may be more diversity.
In terms of identifying tailored strategies based on ethnicity, as we have for essential hypertension, we would like to tailor therapy to the individual, but PAH is relatively rare compared [with] other diseases. This has hampered our ability to develop studies to identify ethnic differences for therapy. As more information is available on the genetic and physical manifestations of this syndrome, we will need additional studies to evaluate tailored therapies.
Pulmonology Advisor: Why has it been difficult to recruit ethnic and racial minorities for clinical trials?
Dr de Jesus Perez: Large tertiary care centers do not attract patients who have limited access to the healthcare system. Sometimes patients do not have insurance or they may have been misdiagnosed, so they never make it to the tertiary care centers for further treatment.
Patients fear that they will be treated like guinea pigs or receive less than the standard of care if they enroll in a clinical trial.6 Limited education and language barriers also preclude minority patients from participating in trials.
Dr Hill: Problems with transport and access to centers doing clinical trials may be factors. Also, patients from different cultures or ethnicities may be distrustful of researchers who are largely white and English speaking. Considering the history of research on minorities from a century ago, this is perhaps not too surprising.6
Dr Test: Clinical trials tend to reflect the ethnic diversity of a particular country. In the large national registries, Hispanic and Asian patients have not been as prevalent as we would expect. Recruitment of patients into studies is challenging and reflects socioeconomic factors such as access to health care. The more recent multinational pharmaceutical trials have lessened this impact somewhat, but we need to improve patient recruitment of all ethnicities.
Pulmonology Advisor: Is there anything you were expecting Pulmonology Advisor to address, but did not?
Dr de Jesus Perez: We are aware that [treatment of minority populations] is a problem, and we will be addressing it by educating clinicians through the American Thoracic Society statement and at presentations during the upcoming Pulmonary Hypertension Association and American Thoracic Society meetings.
Dr Test: I would suggest focusing on the concept that PAH is not a disease but a syndrome. The root cause of PAH determines how a patient is treated. Ethnicity strongly [affects] risk factors such as essential hypertension, diabetes, and renal disease that are associated with the development of pulmonary venous hypertension.
Please note: This interview was edited for clarity.
Summary & Clinical Applicability
Clinicians are eager for more evidence regarding differences in patients with PAH from diverse ethnic and racial backgrounds to better inform their treatment options. During the next year, clinician and patient groups will raise awareness about the necessity of including patients who were previously underrepresented in clinical trials to better inform management of this rare and often fatal disease.
Limitations & Disclosures
- Galiè N, Humbert M, Vachiery JL, et al. 2015 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension: The Joint Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS): Endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC), International Society for Heart and Lung Transplantation (ISHLT). Eur Heart J. 2016;37:67-119.
- Medrek SK, Sahay S. Ethnicity in pulmonary arterial hypertension: possibilities for novel phenotypes in the age of personalized medicine [published online September 5, 2017]. Chest. doi:10.1016/j.chest.2017.08.1159
- Al-Naamani N, Paulus JK, Roberts KE, et al. Racial and ethnic differences in pulmonary arterial hypertension [published online September 15, 2017]. Pulm Circ. doi:10.1177/2045893217732213
- Hill NS, Cawley MJ, Heggen-Peay CL. New therapeutic paradigms and guidelines in the management of pulmonary arterial hypertension. J Manag Care Spec Pharm. 2016;22(3 Suppl A):S3-S21.
- Taichman DB, Ornelas J, Chung L, et al. Pharmacologic therapy for pulmonary arterial hypertension in adults: CHEST guideline and expert panel report. Chest. 2014;146(2):449-475.
- Harris Y, Gorelick PB, Samuels P, Bempong I. Why African Americans may not be participating in clinical trials. J Natl Med Assoc. 1996;88(10):630-634.