Sleep-Disordered Breathing in Precapillary Pulmonary Hypertension: Is the Prevalence So High?

Dear Editor,We read with great interest the excellent study by Spiesshoefer et al. [1], one of the largest studies on the prevalence of sleep-disordered breathing in patients with pulmonary hypertension (PH), along with the state-of-the-art assessment (regarding cardiac MRI studies) of its potential clinical consequences. The prevalence of obstructive sleep apnea (OSA) increased in stable PH patients: 48 of 71 precapillary PH patients developed OSA (68%), which is very high (polygraphic recordings underestimate the prevalence of OSA compared to polysomnographic recordings), and OSA appeared (p < 0.01) in 2 of 35 control group patients (5%). The presence of OSA was not associated with daytime symptoms of SDB or cardiac dysfunction measures. OSA acutely increases sympathetic nerve activity and pulmonary artery pressure (via negative intrathoracic pressure and hypoxemia), likely acting detrimentally on the right ventricle [2, 3]. However, the increase in pulmonary pressure caused by OSA in patients without PH is usually under 10 mm Hg [2], and it remains unknown whether this is clinically meaningful in PH [4].This study does not provide a formula for calculating the sample size of the prevalence survey. We are curious whether the sample size was sufficient for calculating the prevalence rate, and why the authors did not include the third type of PH associated with hypoxia. The prevalence rate of this article was not sufficiently rigorous because the denominator of the rate should be the whole population, but the denominator here is more like a selected population, and the composition ratio of the article is more appropriate. No statistically significant difference in hypercapnic ventilatory response was found between PH patients with and without OSA, and there was no significant difference between PH patients with and without OSA in self-reported daytime sleepiness (ESS score), sleep quality (PSQI composite score), and cardiopulmonary function (including plasma NT-proBNP). These results differ slightly from our usual understanding of OSA.The reason for the high prevalence of OSA (68%) in PH patients in this study may be related to the following conditions: (1) possible selection bias during patient inclusion and (2) patients’ decreased blood oxygen, which can cause a PH-related blood oxygen drop to be regarded as apnea or hypopnea. Howden et al. [5] demonstrated that PH patients show significant impairment in every step of the oxygen (O2) utilization cascade, resulting in markedly impaired exercise capacity. Pulmonary vascular intervention increases peak oxygen uptake (VO2) by partly correcting O2 delivery but has no impact on abnormalities in peripheral O2 extraction. This suggests that current interventions only partially address patients’ limitations, and additional therapies may improve functional capacity.In conclusion, this article brilliantly reveals that nocturnal hypoxemia is a frequent finding which relates to structural right ventricle remodeling in PH (in contrast with OSA). We suggest that these prevalence results should be interpreted with caution as the high prevalence of OSA will lead to an unnecessary psychological burden in PH patients. Whether moderate to severe OSA in PH patients should be treated with CPAP requires further research.We would like to thank Professor Nanshan Zhong from State Key Laboratory of Respiratory Disease for the constructive advice he gave.The article is exempt from ethical committee approval as it is a letter to the editor commenting on a recently published article.All authors have seen and approved the manuscript. The authors have no conflicts of interest.This work was supported by the Natural Science Foundation of Guangdong Province (No. 2021A1515011373) and the Zhongnanshan Medical Foundation of Guangdong Province, Penghua Care Fund to the Medical Pioneers against COVID-19 of Shenzhen Social Commonweal Foundation (2020B1111340010).Z.Z.Z., R.K.C., and C.H.L. contributed to conception of the manuscript; J.M.L. and H.M.L. contributed to draft preparation; and C.H. and N.F.Z. contributed to critical revision. All authors approved the final version to be published.Zhenzhen Zheng, Riken Chen, and Chunhe Li contributed equally to this work.