Incidence of PAH Is 5.8 New Cases Per Million People, Review Finds

A total of approximately 5.8 new cases per one million inhabitants was found to be the most accurate value for the worldwide incidence of pulmonary arterial hypertension (PAH), according to a review study.

That incidence value — the rate of occurrence of new cases of a disease — ranged from 1.5 to 32 PAH patients per million people, the results showed.

Other reliable epidemiological values for PAH and chronic thromboembolic pulmonary hypertension (CTEPH) were reported in the study, which may improve the detection of new cases, researchers said.

Titled “Epidemiology of pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension: identification of the most accurate estimates from a systematic literature review,” the study was published in the journal Pulmonary Circulation.

PAH and CTEPH have had wide ranges of estimates for both incidence and prevalence — the total number of disease cases — over the past years. In spite of efforts made to improve awareness, diagnosis, and clinical management of these rare diseases, it is not clear which of the current estimates might prove most reliable.

This is important because accurate estimates would help doctors and scientists to assess the probability of PAH and CTEPH being underdiagnosed, thereby helping to improve disease detection.

Now, researchers at Actelion Pharmaceuticals, part of Janssen Pharmaceutical, conducted a review of published studies and reports on PAH and CTEPH incidence and prevalence. Their goal was to identify the most accurate estimates.

In total, the team analyzed 33 studies, most of them based on European data, published between January 2003 and August 2020. Very few included children. Among the studies, 15 involved PAH and seven CTEPH, with 11 including both diseases.

The studies were classified into three categories: registries, or population-based estimates; medical records, specifically hospital-based estimates; or administrative claim data. Further, the registries were divided into systematic and non-systematic, based on whether or not they were based on national systematic registry data from centralized healthcare systems.

The patients’ mean age ranged between 43 and 67 for those with PAH, and between 58 and 73 for those with CTEPH.

In adults with PAH, the incidence varied from 1.5 to 32 patients per million (ppm) and prevalence from 12.4 to 268 ppm. Similarly, in adults with CTEPH, the ranges of incidence were from 0.9 to 39 ppm and prevalence from 14.5 to 144 ppm.

Researchers believe this variation could be due to geographic differences in PAH and CTEPH populations.

“The geographic variation of disease estimates may be the consequence of differences in healthcare systems and patient tracking,” they wrote.

Clinical practices also differ from country to country, the researchers noted, which also may have influenced the numbers found.

“Confirmation of PH/PAH diagnosis by RHC [right heart catheterization] is the gold standard” as per the current European Society of Cardiology/European Respiratory Society (ESC/ERS) guidelines, the investigators wrote.

“In countries where RHC or V/Q [ventilation–perfusion] scanning are either unavailable or not systematically used, estimates of epidemiology can be less accurate due to misdiagnosis,” they wrote.

The variability in the estimates also may be explained by the type of data source used. According to the team, the numbers given by administrative claim data may be overestimated.

“Large claims/administrative databases were used by several authors, despite the limitation of unconfirmed PAH or CTEPH diagnosis with this study type,” the researchers wrote.

Only seven studies included children. An analysis of them showed the disease incidence for children with PAH ranged from 2.4 to 16.7 ppm, and prevalence from 3.7 to 397 ppm. Regarding CTEPH, the majority of the studies estimated the incidence and prevalence to be lower than 1 ppm.

According to the team, PAH and CTEPH are mainly diagnosed in older patients, which may explain the lack of epidemiological studies with children.

“Paediatric PAH and CTEPH are rare forms of rare conditions and the relative lack of research into paediatric cases of rare diseases is still being addressed,” the researchers wrote.

Overall, there were variations between data from centralized healthcare systems and administrative claims.

Studies based on data from centralized systems showed that the incidence of PAH in adults was approximately 5.8 ppm and the prevalence varied from 47.6 to 54.7. Regarding CTEPH, the same studies reported a range of 3.1 to 6.0 ppm for incidence and 25.8 to 38.4 ppm for prevalence.

According to the scientists, these estimates were the most trustworthy, and better used in research, as they are provided by national systematic registries.

“Registries have the advantage of being designed with the purpose of supporting scientific research for a specific disease and, as such, only patients with a confirmed diagnosis should be included,” the researchers wrote.

“These estimates could be used as a guide or threshold level to assess if a country is likely to be under-diagnosing PAH and CTEPH. This would help to set detection rate goals and guide allocation of research grants and healthcare resources by decision-makers,” the team concluded.