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The New Face of Pulmonary Arterial Hypertension


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Thenappan Thenappan, MD
University of Minnesota Medical Center
Minneapolis, MN, USA
tthenapp@umn.edu




Pulmonary arterial hypertension (PAH) is characterized by proliferation and remodeling of the small pulmonary arteries, leading to increased pulmonary vascular resistance and ultimately right ventricular failure and death. The classic textbook description of idiopathic pulmonary arterial hypertension is it more commonly affects middle-aged female. This comes from the historic National Institutes of Health (NIH) registry from the 1980's [1]. The mean age of the patients enrolled in the NIH registry was 36 and the female to male ratio was 1.7: 1. Their 1-, 3-, and 5- year survival were 67%, 45%, and 37% respectively prior to the approval of currently available PAH-specific therapies [1].

Data from several contemporary PAH registries from different parts of the world suggest that the epidemiology of PAH has changed significantly in the last 3 decades [2-6]. The mean age of the patients enrolled in the contemporary registries ranged from 48-53 years, which is significantly higher when compared to the NIH registry, and there was an increase in the female to male ratio [2-6]. In addition, patients in the modern registries had a better survival when compared to the patients in the landmark NIH registry. A possible explanation for the difference is the predominance of prevalent cases in the contemporary registries. Over representation of prevalent cases (~ 85%), who have survived for reasons including intrinsic variation in disease lethality and/or the effects of therapy, could potentially introduce survivor bias. However, recent analysis from the pulmonary hypertension registry of the United Kingdom and Ireland revealed that even in treatment-naïve incident PAH patient population, the mean age at the time of diagnosis in the current era is significantly higher [5]. This registry prospectively followed 482-treatment naïve patients diagnosed with idiopathic, familial, or anorexigen-associated PAH between 2001-2009. The median age at the time of enrollment in the registry was 50 years, and 13.5% were actually older than 70 years of age at the time of diagnosis. These patients also had significantly higher comorbidities including hypertension, diabetes, atrial fibrillation, and coronary artery disease5. These data clearly indicate that the current face of PAH is different when compared to the 1980's.

There is no clear explanation for the change in the demographic of PAH in the current era. One intriguing question is whether pulmonary hypertension in the elderly (>50 years) is truly a different phenotype of PAH or is it a classification drift. Are we misclassifying patients with pulmonary hypertension associated with heart failure with preserved ejection fraction as PAH due to overreliance on a single measurement of a resting pulmonary capillary wedge pressure? This question raises since the phenotype of the elderly patients diagnosed with PAH based on the current diagnostic criteria (mean pulmonary artery pressure > 25 mm Hg and resting pulmonary capillary wedge pressure <=15 mm Hg) shares several similar characteristics with pulmonary hypertension associated with heart failure preserved ejection fraction - both groups have increased incidence of comorbidities including hypertension, diabetes, atrial fibrillation, and ischemic heart disease [5,7]; the severity of pulmonary hypertension is only moderate as opposed to severe as in younger patients with PAH [5,7]; and finally survival in both groups is worse as compared to younger patients with PAH, despite the presence of only moderately severe pulmonary hypertension. The differentiation between PAH and pulmonary hypertension associated with heart failure with preserved ejection fraction is important since the treatment and prognosis significantly differs between the two diagnoses. Further studies are needed in the future to better differentiate aging PAH from pulmonary hypertension associated with heart failure with preserved ejection fraction, and also to assess the response to PAH-specific therapies in elderly patients with PAH.

Disclosure Statement: the author has no conflicts of interest to report.


References:

  1. Rich S, Dantzker R, Ayres S, et al. Primary pulmonary hypertension: a national prospective study. Ann Intern Med. 1987;107:216-223.
  2. Badesch DB, Raskob GE, Elliott CG, et al. Pulmonary arterial hypertension: baseline characteristics from the REVEAL Registry. Chest. Feb 2010;137(2):376-387.
  3. Humbert M, Sitbon O, Chaouat A, et al. Pulmonary arterial hypertension in france: results from a national registry. Am J Respir Crit Care Med. May 1 2006;173(9):1023-1030.
  4. Jing ZC, Xu XQ, Han ZY, et al. Registry and Survival Study in Chinese Patients With Idiopathic and Familial Pulmonary Arterial Hypertension. Chest. Aug 2007;132(2):373-379.
  5. Ling Y, Johnson MK, Kiely DG, et al. Changing demographics, epidemiology, and survival of incident pulmonary arterial hypertension: results from the pulmonary hypertension registry of the United Kingdom and Ireland. Am J Respir Crit Care Med. Oct 15 2012;186(8):790-796.
  6. Thenappan T, Shah SJ, Rich S, Gomberg-Maitland M. A USA-based registry for pulmonary arterial hypertension: 1982 2006. Eur Respir J. Dec 2007;30(6):1103-1110.
  7. Thenappan T, Shah SJ, Gomberg-Maitland M, et al. Clinical characteristics of pulmonary hypertension in patients with heart failure and preserved ejection fraction. Circ Heart Fail. May;4(3):257-265.



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