More PAH Cases in US Southwest than Registry Reports, Study Says

The number of both new and existing cases of pulmonary arterial hypertension (PAH) in the southwestern U.S. population was found in a recent study to be higher than that reported in the largest U.S. PH registry, called REVEAL, or the Registry to Evaluate Early and Long-term PAH.

The study also pointed out that Hispanic and Native American patients are underrepresented in the national registry, although neither minority was found to have greater PAH prevalence — the number of existing cases of a disease — compared with Caucasian patients.

Moreover, living at a higher altitude was found to be associated with PAH. But this observation warrants further study and input from other PAH centers, the researchers said.

Titled “High geographic prevalence of pulmonary artery hypertension: associations with ethnicity, drug use, and altitude,” the study was published in the journal Pulmonary Circulation.

PAH, part of group 1 in the World Health Organization (WHO) classification of pulmonary hypertension, can have several causes, including congenital heart disease, exposure to certain drugs and toxins, and connective tissue diseases (CTDs). It also can be of unknown cause, and thus called idiopathic PAH.

Registries like REVEAL, for PAH, are important to better understand the demographics, causes, and distribution of the disease in different populations. They also are used by researchers in designing clinical trials for testing current and future treatments.

The REVEAL registry is the largest in the U.S., reporting an estimated incidence — the number of new cases reported within a specific time period — of PAH in adults of 2.3 cases per million. The prevalence of PAH is 12.4 cases per million, according to REVEAL.

Now, the researchers at a single PAH specialty clinic in New Mexico, in the southwestern U.S., sought to further describe the disease burden and characteristics of adults with PAH in their center. Of note, the population seen at this clinic also includes patients from two ZIP codes in Arizona and one in Texas.

“Clinical experience at our institution suggested disease prevalence greater than these previous population-level descriptions of PAH,” the researchers said.

The team also aimed to provide specific, relevant data on minorities, namely Hispanics and Native Americans, both underrepresented in the REVEAL study. Of relevance, native Americans are absent from any prior PAH registry. Ethnicity is thought to play a role in both the symptoms and outcomes of PAH, and a recent study in North America found significant variability of PH subtypes and survival among children of different racial and ethnic groups.

The association of PAH with altitude and known toxins and drugs were other potential links examined by the researchers. Altitude has been considered a possible contributing factor for PAH, due to hypoxia, or low oxygen, and its effects on pulmonary artery pressures.

A total of 154 PAH patients, analyzed at the southwestern center in 2016, were included in the retrospective study. The patients’ mean age was 58.3 years, with 60.4% age 64 or younger; 70.8% were female.

The team calculated the prevalence of PAH in this group at 93 cases per million, which is significantly greater than in the REVEAL registry. Likewise, incidence was established at 14 cases per million, also significantly greater than that observed in the REVEAL registry.

According to the team, at least part of this marked difference is attributed to the underestimation of PAH prevalence and incidence in the REVEAL registry.

“REVEAL study investigators are forthright about these and other limitations,” the researchers said.

Racial and ethnic distribution revealed that less than half of the patients in the southwestern center’s group were white (48.7%). Hispanics were the next most represented ethnicity/race at 35.7%, followed by Native Americans at 10.4%. This was significantly different from the REVEAL study.

“Our cohort contained significantly more Hispanic and fewer white and fewer black patients than the REVEAL cohort,” the researchers said. However, the percentage of Hispanic patients in the center’s PAH group was still significantly lower relative to the total at-risk population (48.4%) in the area analyzed.

Data on Native Americans was combined with that of the Asian population — since no specific data is available in REVEAL regarding Native Americans — and corresponded to a previously published racial/ethnic group named “other.” The percentage of “other” was found to be higher than in the REVEAL cohort, but this difference was not significant.

“Neither group demonstrated prevalence greater than among whites, indicating that neither Hispanic nor Native American populations specifically contributed to the overall increased prevalence of PAH in our cohort,” the team said.

The most common PAH-associated condition in the group analyzed was CTDs (34.4%), followed by idiopathic PAH, or IPAH (29.6%), and exposure to drugs and toxins (20.7%). In this group, most patients (26 patients, 16.8%) had been exposed to drugs and toxins categorized as definite causes of PAH, most commonly amphetamines and methamphetamines (22 patients).

In comparison with the REVEAL study, IPAH was significantly less common in this southwestern group, and drug/toxins exposure was significantly higher.

“Public health data from our state indicates exposure rates to methamphetamine above the U.S. national average, raising the possibility of its contribution to PAH in our patient cohort,” the researchers said.

Concerning altitude, the team found 152 cases in the group from ZIP codes with mean altitudes greater than 4,000 ft. Four of the individuals resided at very high altitude, above 2,500 m (about 8,202 ft).

However, given the existence of several other variables, the researchers did not make any final determinations about this factor.

“Our data are insufficient to draw definitive conclusions about the effects of moderate altitude on PAH burden,” they said.

The team emphasized that more studies are needed in centers at different altitudes.