Prevalence, causes, clinical characteristics and diagnostic challenges associated with pulmonary hypertension in African and African-Americans

Introduction

 Pulmonary hypertension (PH) is defined as a resting mean pulmonary arterial pressure (PAP) of greater than 25 mm Hg at rest or 30 mm Hg on exercise. Although right heart catheterization is mandatory to make the diagnosis, it is not always feasible or practical to perform in daily practice. Alternatively, due to its easy accessibility and non-invasive nature, Doppler echocardiography is frequently used as a screening tool for PH in populations to estimate the pulmonary arterial systolic pressure.

Pulmonary hypertension is associated with increased morbidity and mortality, with clear cost implications from recurrent hospital admissions, prolonged hospital stay and chronic medical use. Left heart disease^1-3 and chronic pulmonary diseases^4-6 are well-recognized risk factors for PH and are prevalent in the minorities, including the African or African-American community.^7-10 The clinical classification of pulmonary hypertension was revised to identify five major groups (Table 1).^11,12 The cause of PH is of critical importance as it defines subsequent treatment options, and those with pulmonary arterial hypertension (Table 1, group 1)^11,12 can be treated with selective pulmonary arterial vasodilators. Yet there is often a delay from first symptoms to diagnosis⁴ , as making the diagnosis of pulmonary hypertension can be challenging. This delay can impact negatively on the overall management of PH patients.

Epidemiology of pulmonary hypertension in the minority populations

Generally there has been very little data regarding the prevalence of pulmonary hypertension in the general and the minority populations, including African or African-Americans. The prevalence of PH was previously reported at 6.8% in community-based and larger populations, of which the majority were Caucasian (6.6%).^13,14 Consistent with a recent report¹⁵, African-American patients had a significantly higher prevalence of pulmonary hypertension compared to other races, both in the entire study population and in patients with idiopathic interstitial pneumonitis (IIP). In the same report, the association or prevalence of pulmonary hypertension in the African-American race was observed in other forms of PH as well. In idiopathic PH, African-American patients demonstrated a substantially increased mortality rate compared with Caucasian patients.¹⁶ Pulmonary hypertension tends to frequently develop at an earlier age in African-American patients with systemic sclerosis. These patients are more likely to have interstitial lung disease-associated pulmonary hypertension, and have a poorer survival compared with Caucasian patients.^17,18 Due to health care disparities between races, African-Americans may be more likely to be uninsured, have less comprehensive health insurance benefits, and lack adequate access to care and costly treatments than other racial groups. Past research indicates a greater percentage of African-Americans than caucasians dying of PH, a difference which has increased over the past twenty years. Another study showed a higher risk of death for African-Americans with pulmonary arterial hypertension (PAH) compared with other racial groups, even after consideration of severity of disease and use of therapies.

The cause for these differences in outcomes in developed countries is unknown.¹⁶ Much of the statistical evidence on PH among people of African descent is based on death rates, indicating a lack of diagnosis while there is still a chance to save lives. Pulmonary hypertension was also reported to be common among heart failure patients, and was associated with worse outcomes among Africans. It is recommended that patients presenting with heart failure or symptoms be screened for pulmonary hypertension, and most importantly, precautions should be taken immediately in the presence of pulmonary hypertension in terms of management and for prognostic purposes.¹⁹ Additional epidemiologic initiatives also are needed to ascertain prevalence and incidence of various PH disease entities such as pulmonary arterial hypertension. In a study presented at CHEST 2006, the 72nd annual international scientific assembly of the American College of Chest Physicians (ACCP) revealed that racial disparities exist in PH mortality and morbidity, with African-American women exhibiting the highest mortality rate when compared with all other groups.

Causes of pulmonary hypertension in Africans and African-Americans

Left heart disease^1-3,20 and chronic pulmonary diseases^4-6 are well-known and common risk factors for pulmonary hypertension and are prevalent in the African and African-American community.^7-10,14,21 The existing reports from studies have demonstrated an increased prevalence of PH with increasing age and are independent of comorbidities and cardiopulmonary function. The prevalence ratio increases 10 times in older people compared to those of a younger age ( >65 versus 45 years).^1,14,22 Risk factors for increased left atrial pressure are also associated with increased risk for pulmonary hypertension and other related diseases, such as systemic hypertension, diabetes and obesity, in Africans or African-American populations.^23-25 According to some African reports, human immunodeficiency virus (HIV) is emerging as one of the most common and important causes of pulmonary hypertension in Africans. In some studies, both sexes were affected by idiopathic PAH, whereas significantly more women were affected by HIV and connective tissue related PAH. Based on the Heart of Soweto study, the majority of these cases were of African descent and originated from somewhere other than Soweto, which is more urban. In the same report, women were almost two-fold more likely to present with PAH while those with low levels of education and originating from urban areas were less likely to present with PAH compared with those with higher levels of education.²⁶

Demographic & Clinical Characteristics Associated With PH

Based on previous reports, the prevalence ratio of pulmonary hypertension increases with age, female, being obese, or having diabetes, higher pulse pressure, severe left heart valve disease or chronic lung disease.^14,27 All these are some of the parameters to look for in daily clinical practice when evaluating a patient with (or suspected of having) PH. Pulmonary hypertension is characterized by insidious onset and progressive clinical deterioration. The symptomatology of PH could be very diverse and non-specific. These symptoms would include dyspnea of breath, episodes of chest pains, generalized fatigue, dizziness or syncope, cough and palpitations.^28-32 Dyspnea has been reported as the most frequently encountered symptom and most importantly the clinical signs in these patients are predominantly those of right sided heart failure. However, the clinical signs are also guided by the chronicity and severity of pulmonary hypertension. Due to lack of access to health facilities and poor socioeconomic backgrounds in most of the minority populations, patients tend to be symptomatic for a longer period of time before they present to the health centers for medical attention. Unfortunately, this means that the window to identify these patients earlier and plan their management accordingly is significantly smaller.

Diagnostic Evaluation of pulmonary hypertension, are there any differences?

I.Screening and Diagnostic evaluation

The diagnostic approach for PH should be applied similarly; however this should be guided by the clinical setting and the attending clinicians’ judgment. Patients with PH must be evaluated using a multimodality approach to ensure a correct diagnosis and basal evaluation as well as a prognostic assessment. The standard transthoracic echocardiographic examination remains the first line of multimodality imaging and this allows for the evaluation of pulmonary pressure and right ventricular changes in relation to high afterload. However, other imaging modalities are widely used as part of the standard protocol, and include Chest-XR and CT scans (including high resolution computer tomography: HRCT).

II. Noninvasive estimation of pulmonary arterial pressure (PAP) using transthoracic echocardiography (TTE)

With the existence and easy accessibility to standard two-dimensional echocardiography, particularly Doppler echocardiography, the assessment of pulmonary arterial pressures is quite feasible. However, because of its intrinsic operator dependency, screening can be challenging.^33,34 Transthoracic echocardiography remains the most financially viable and easily accessible modality in the minority population, especially in the rural communities. Yet the challenges remains, as some hospitals lack echocardiography, whilst other centers that have access to this tool still struggle with a lack of expertise in this technology. As such, difficulties remain in the screening and diagnosis of early pulmonary hypertension in most of these patients. However, some of the most important technical challenges include the presence of a tricuspid insufficiency.

III. Exercise Echocardiography

Exercise echocardiography is one of the advanced echocardiographic modalities that is used to assess systolic PAP in several groups of patients. It is predominantly used in patients with chronic lung diseases, congenital heart diseases (including atrial septal defects), valvular heart diseases, cardiac transplantation, and high altitude pulmonary diseases. Exercise echocardiography should be used in PH.

IV. New modalities in noninvasive screening

Cardiac magnetic resonance (CMR) is a reliable modality and can be used both at rest and during exercise or acute vasodilator testing. However, its use as a routine screening test is not mandatory.

V. Biochemical Markers

Biomarkers, such as brain natriuretic peptide (BNP) and N-terminal pro-brain natriuretic peptide (NT-proBNP), may be quite useful in early detection of PAH. The BNP can be used both for monitoring and prognostication depending on the patient’s symptomatology and disease stage. It is important to note that the incidences of PH and clinical characteristics may differ because PH is commonly associated with other conditions, which are also associated with elevated BNP.

VI. Genetic Testing

Performing testing for genetic mutations should be guided by the clinical scenario, as these could have potential risks and benefits following the tests. There are limitations with accessibility of the tests and results thereof. It might be very difficult in some centers for genetic testing and counseling. The molecular testing should ideally be performed in clinically approved and certified molecular genetics laboratory, which may not be available in some centers. This poses a huge challenge to genetic screening as part of the work up for PH.

Conclusion

Pulmonary hypertension (PH) is a common entity and can easily be detected with the implementation of echocardiography. PH has been reported to be quite prevalent in minority populations, in particular the African and African-American populations, and more so in women. Apart from the common risk factors for PH, age, chronic obstructive lung disease, and significant left-sided heart diseases (including valvular heart disease), are some of the most common and important determinants of PH in the minority populations. The presence and severity of PH is associated with poor outcomes in African-Americans with underlying cardiopulmonary disease. As a result, it is very important to promptly identify these patients very early in the course of the disease. The better outcomes will obviously be influenced by early diagnosis and treatment.

References

1. Lam CS, Borlaug BA, Kane GC, Enders FT, Rodeheffer RJ, Redfield MM. Age-associated increases in pulmonary artery systolic pressure in the general population. Circulation. 2009;119:2663-2670

2. Abramson SV, Burke JF, Kelly JJ, Jr., Kitchen JG, 3rd, Dougherty MJ, Yih DF, McGeehin FC, 3rd, Shuck JW, Phiambolis TP. Pulmonary hypertension predicts mortality and morbidity in patients with dilated cardiomyopathy. Ann Intern Med. 1992;116:888-895

3. Kjaergaard J, Akkan D, Iversen KK, Kjoller E, Kober L, Torp-Pedersen C, Hassager C. Prognostic importance of pulmonary hypertension in patients with heart failure. Am J Cardiol. 2007;99:1146-1150

4. Chaouat A, Naeije R, Weitzenblum E. Pulmonary hypertension in copd. Eur Respir J. 2008;32:1371-1385

5. Kessler R, Faller M, Fourgaut G, Mennecier B, Weitzenblum E. Predictive factors of hospitalization for acute exacerbation in a series of 64 patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 1999;159:158-164

6. Oswald-Mammosser M, Weitzenblum E, Quoix E, Moser G, Chaouat A, Charpentier C, Kessler R. Prognostic factors in copd patients receiving long-term oxygen therapy. Importance of pulmonary artery pressure. Chest. 1995;107:1193-1198

7. Mannino DM, Homa DM, Akinbami LJ, Ford ES, Redd SC. Chronic obstructive pulmonary disease surveillance--united states, 1971-2000. MMWR Surveill Summ. 2002;51:1-16

8. Mannino DM. Copd: Epidemiology, prevalence, morbidity and mortality, and disease heterogeneity. Chest. 2002;121:121S-126S

9. Roger VL, Go AS, Lloyd-Jones DM, Benjamin EJ, Berry JD, Borden WB, Bravata DM, Dai S, Ford ES, Fox CS, Fullerton HJ, Gillespie C, Hailpern SM, Heit JA, Howard VJ, Kissela BM, Kittner SJ, Lackland DT, Lichtman JH, Lisabeth LD, Makuc DM, Marcus GM, Marelli A, Matchar DB, Moy CS, Mozaffarian D, Mussolino ME, Nichol G, Paynter NP, Soliman EZ, Sorlie PD, Sotoodehnia N, Turan TN, Virani SS, Wong ND, Woo D, Turner MB. Heart disease and stroke statistics--2012 update: A report from the american heart association. Circulation. 2012;125:e2-e220

10. Roger VL, Go AS, Lloyd-Jones DM, Adams RJ, Berry JD, Brown TM, Carnethon MR, Dai S, de Simone G, Ford ES, Fox CS, Fullerton HJ, Gillespie C, Greenlund KJ, Hailpern SM, Heit JA, Ho PM, Howard VJ, Kissela BM, Kittner SJ, Lackland DT, Lichtman JH, Lisabeth LD, Makuc DM, Marcus GM, Marelli A, Matchar DB, McDermott MM, Meigs JB, Moy CS, Mozaffarian D, Mussolino ME, Nichol G, Paynter NP, Rosamond WD, Sorlie PD, Stafford RS, Turan TN, Turner MB, Wong ND, Wylie-Rosett J. Heart disease and stroke statistics--2011 update: A report from the american heart association. Circulation. 2011;123:e18-e209

11. Simonneau G, Robbins IM, Beghetti M, Channick RN, Delcroix M, Denton CP, Elliott CG, Gaine SP, Gladwin MT, Jing ZC, Krowka MJ, Langleben D, Nakanishi N, Souza R. Updated clinical classification of pulmonary hypertension. J Am Coll Cardiol. 2009;54:S43-54

12. Galie N, Hoeper MM, Humbert M, Torbicki A, Vachiery JL, Barbera JA, Beghetti M, Corris P, Gaine S, Gibbs JS, Gomez-Sanchez MA, Jondeau G, Klepetko W, Opitz C, Peacock A, Rubin L, Zellweger M, Simonneau G. Guidelines for the diagnosis and treatment of pulmonary hypertension. Eur Respir J. 2009;34:1219-1263

13. Enea I, Ghio S, Bongarzoni A, Casazza F, D’Armini AM, Favretto G, Roncon L, Rubboli A, Serafini O, Zonzin P, D’Agostino C. [echocardiographic alterations suggestive of pulmonary hypertension in the italian ultrasonography laboratories. Epidemiological data from the incipit study (incidence of pulmonary hypertension in italian ultrasonography laboratories)]. G Ital Cardiol (Rome). 2010;11:402-407

14. Choudhary G, Jankowich M, Wu WC. Prevalence and clinical characteristics associated with pulmonary hypertension in african-americans. PLoS One. 2013;8:e84264

15. Shorr AF, Wainright JL, Cors CS, Lettieri CJ, Nathan SD. Pulmonary hypertension in patients with pulmonary fibrosis awaiting lung transplant. Eur Respir J. 2007;30:715-721

16. Davis KK, Lilienfeld DE, Doyle RL. Increased mortality in african americans with idiopathic pulmonary arterial hypertension. J Natl Med Assoc. 2008;100:69-72

17. Mathai SC, Hummers LK, Champion HC, Wigley FM, Zaiman A, Hassoun PM, Girgis RE. Survival in pulmonary hypertension associated with the scleroderma spectrum of diseases: Impact of interstitial lung disease. Arthritis Rheum. 2009;60:569-577

18. Beall AD, Nietert PJ, Taylor MH, Mitchell HC, Shaftman SR, Silver RM, Smith EA, Bolster MB. Ethnic disparities among patients with pulmonary hypertension associated with systemic sclerosis. J Rheumatol. 2007;34:1277-1282

19. Karaye KM, Saidu H, Bala MS, Yahaya IA. Prevalence, clinical characteristics and outcome of pulmonary hypertension among admitted heart failure patients. Ann Afr Med. 2013;12:197-204

20. Ghio S, Gavazzi A, Campana C, Inserra C, Klersy C, Sebastiani R, Arbustini E, Recusani F, Tavazzi L. Independent and additive prognostic value of right ventricular systolic function and pulmonary artery pressure in patients with chronic heart failure. J Am Coll Cardiol. 2001;37:183-188

21. Mannino DM, Homa DM, Akinbami LJ, Moorman JE, Gwynn C, Redd SC. Surveillance for asthma--united states, 1980-1999. MMWR Surveill Summ. 2002;51:1-13

22. Hyduk A, Croft JB, Ayala C, Zheng K, Zheng ZJ, Mensah GA. Pulmonary hypertension surveillance--united states, 1980-2002. MMWR Surveill Summ. 2005;54:1-28

23. Poirier P, Garneau C, Bogaty P, Nadeau A, Marois L, Brochu C, Gingras C, Fortin C, Jobin J, Dumesnil JG. Impact of left ventricular diastolic dysfunction on maximal treadmill performance in normotensive subjects with well-controlled type 2 diabetes mellitus. Am J Cardiol. 2000;85:473-477

24. Poirier P, Bogaty P, Garneau C, Marois L, Dumesnil JG. Diastolic dysfunction in normotensive men with well-controlled type 2 diabetes: Importance of maneuvers in echocardiographic screening for preclinical diabetic cardiomyopathy. Diabetes Care. 2001;24:5-10

25. Russo C, Jin Z, Homma S, Rundek T, Elkind MS, Sacco RL, Di Tullio MR. Effect of obesity and overweight on left ventricular diastolic function: A community-based study in an elderly cohort. J Am Coll Cardiol. 2011;57:1368-1374

26. Brooksbank R, Woodiwiss AJ, Sliwa K, Badenhorst D, Deftereos D, Wadee AA, Essop MR, Sareli P, Norton GR. Endotoxin-independent white cell cytokine production in haemodynamically stable patients with idiopathic dilated cardiomyopathy. Cardiovasc J S Afr. 2005;16:260-265

 27. Guglin M, Kolli S, Chen R. Determinants of pulmonary hypertension in young adults. Int J Clin Pract Suppl. 2012:13-19

28. Rich S, Dantzker DR, Ayres SM, Bergofsky EH, Brundage BH, Detre KM, Fishman AP, Goldring RM, Groves BM, Koerner SK, et al. Primary pulmonary hypertension. A national prospective study. Ann Intern Med. 1987;107:216-223

29. Wagenvoort CA, Oakley CM. Management of primary pulmonary hypertension. Br Heart J. 1985;54:554-555

30. Oakley CM. Management of primary pulmonary hypertension. Br Heart J. 1985;53:1-4

31. D’Alonzo GE, Bower JS, Dantzker DR. Differentiation of patients with primary and thromboembolic pulmonary hypertension. Chest. 1984;85:457-461

32. Perloff JK. Auscultatory and phonocardiographic manifestations of pulmonary hypertension. Prog Cardiovasc Dis. 1967;9:303-340

33. Brecker SJ, Gibbs JS, Fox KM, Yacoub MH, Gibson DG. Comparison of doppler derived haemodynamic variables and simultaneous high fidelity pressure measurements in severe pulmonary hypertension. Br Heart J. 1994;72:384- 389

34. Vachiery JL, Brimioulle S, Crasset V, Naeije R. False-positive diagnosis of pulmonary hypertension by doppler echocardiography. Eur Respir J. 1998;12:1476-1478 www.eurekalert.org/pub_releases/2006-10/acocphd101006.php