Residence at moderately high altitude and its relationship with WHO Group 1 pulmonary arterial hypertension symptom severity and clinical characteristics: the Pulmonary Hypertension Association Registry

Abstract

Background: WHO Group 1 pulmonary arterial hypertension (PAH) is a progressive and potentially fatal disease. Individuals living at higher altitude are exposed to lower barometric pressure and hypobaric hypoxemia. This may result in pulmonary vasoconstriction and contribute to disease progression. We sought to examine the relationship between living at moderately high altitude and PAH characteristics. Methods: Forty-two US centers participating in the Pulmonary Hypertension Association Registry (PHAR) enrolled patients who met the definition of WHO Group 1 PAH. We utilized baseline data and patient questionnaire responses. Patients were divided into two groups: moderately high altitude residence (home >4,000 ft) and low altitude residence (home <4,000 ft) based on zip-code. Clinical characteristics, hemodynamic data, patient demographics and patient reported quality of life metrics were compared. Results: Controlling for potential confounders (age, sex at birth, body mass index (BMI), supplemental oxygen use, race, 100-day cigarette use, alcohol use, and PAH medication use), subjects residing at moderately high altitude had a 6-minute walk distance (6MWD) 32 meters greater than those at low altitude, despite having a pulmonary vascular resistance (PVR) that was 2.2 Wood units (WU) higher. Additionally, those residing at moderately high altitude had 3.7 times greater odds of using supplemental oxygen. Conclusion: Patients with PAH who live at moderately high altitude have a higher PVR and are more likely to need supplemental oxygen. Despite these findings, moderately high altitude PHAR patients have better functional tolerance as measured by 6MWD. It is possible that a “high-altitude phenotype” of PAH may exist. These findings warrant further study.

Inference following multiple imputation for generalized additive models: an investigation of the median p-value rule with applications to the Pulmonary Hypertension Association Registry and Colorado COVID-19 hospitalization data

“…A recent paper [20] examined the effect of home elevation from sea-level (based on ZIP code) on distance walked during six minutes in patients presenting with pulmonary arterial hypertension. The six-minute walk distance (6-MWD) is an important clinical metric used for evaluating progression of disease.…”

On errata and corrigenda—The Pulmonary Hypertension Association Registry (PHAR)

“…Upon review and approval of the proposal, the investigators are provided with a deidentified data set to conduct the proposed analyses. Multiple scientific manuscripts have been published using the PHAR data set focused on patient characteristics, prognostic factors, and outcomes in pulmonary hypertension 4–14 …”

“…All investigators who had included and reported analysis of SF‐12 scores from the PHAR in published manuscripts re‐ran their analyses with the corrected scores. While there were numeric differences in means, medians, and regression coefficients, these changes did not result in significant changes to the published conclusions; however, corrigenda and errata were issued and published by the corresponding journals after communication with the journal editors 15–19 …”

“…Multiple scientific manuscripts have been published using the PHAR data set focused on patient characteristics, prognostic factors, and outcomes in pulmonary hypertension. [4][5][6][7][8][9][10][11][12][13][14] In February 2022, an error in coding involving the SF-12 scoring was discovered. The participant responses were accurate and preserved.…”

“…While there were numeric differences in means, medians, and regression coefficients, these changes did not result in significant changes to the published conclusions; however, corrigenda and errata were issued and published by the corresponding journals after communication with the journal editors. [15][16][17][18][19] To err is human, but mistakes and publication of errata and corrigenda are regarded with seriousness and gravity as they may call into question the integrity of the research. Intentional errors constitute academic misconduct.…”