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. 2022 Apr 1;18(4):983-992.
doi: 10.5664/jcsm.9760.

Risk factors associated with pulmonary hypertension in obesity hypoventilation syndrome

Juan F Masa  1   2   3 , Iván D Benítez  2   4 , Shahrokh Javaheri  5 , Maria Victoria Mogollon  6 , Maria Á Sánchez-Quiroga  2   3   7 , Francisco J Gomez de Terreros  1   2   3 , Jaime Corral  1   2   3 , Rocio Gallego  1   2   3 , Auxiliadora Romero  2   8 , Candela Caballero-Eraso  2   8 , Estrella Ordax-Carbajo  2   9 , María F Troncoso  2   10 , Mónica González  11 , Soledad López-Martín  12 , José M Marin  2   13 , Sergi Martí  2   14 , Trinidad Díaz-Cambriles  2   15 , Eusebi Chiner  16 , Carlos Egea  2   17 , Javier Barca  3   18 , Ferrán Barbé  2   4 , Babak Mokhlesi  19 ; Spanish Sleep Network
Affiliations

Risk factors associated with pulmonary hypertension in obesity hypoventilation syndrome

Juan F Masa et al. J Clin Sleep Med. .

Abstract

Study objectives: Pulmonary hypertension (PH) is prevalent in obesity hypoventilation syndrome (OHS). However, there is a paucity of data assessing pathogenic factors associated with PH. Our objective is to assess risk factors that may be involved in the pathogenesis of PH in untreated OHS.

Methods: In a post hoc analysis of the Pickwick trial, we performed a bivariate analysis of baseline characteristics between patients with and without PH. Variables with a P value ≤ .10 were defined as potential risk factors and were grouped by theoretical pathogenic mechanisms in several adjusted models. Similar analysis was carried out for the 2 OHS phenotypes, with and without severe concomitant obstructive sleep apnea.

Results: Of 246 patients with OHS, 122 (50%) had echocardiographic evidence of PH defined as systolic pulmonary artery pressure ≥ 40 mm Hg. Lower levels of awake PaO2 and higher body mass index were independent risk factors in the multivariate model, with a negative and positive adjusted linear association, respectively (adjusted odds ratio 0.96; 95% confidence interval 0.93 to 0.98; P = .003 for PaO2, and 1.07; 95% confidence interval 1.03 to 1.12; P = .001 for body mass index). In separate analyses, body mass index and PaO2 were independent risk factors in the severe obstructive sleep apnea phenotype, whereas body mass index and peak in-flow velocity in early/late diastole ratio were independent risk factors in the nonsevere obstructive sleep apnea phenotype.

Conclusions: This study identifies obesity per se as a major independent risk factor for PH, regardless of OHS phenotype. Therapeutic interventions targeting weight loss may play a critical role in improving PH in this patient population.

Clinical trial registration: Registry: Clinicaltrial.gov; Name: Alternative of Treatment in Obesity Hypoventilation Syndrome; URL: https://clinicaltrials.gov/ct2/show/NCT01405976; Identifier: NCT01405976.

Citation: Masa JF, Benítez ID, Javaheri S, et al. Risk factors associated with pulmonary hypertension in obesity hypoventilation syndrome. J Clin Sleep Med. 2022;18(4):983-992.

Keywords: CPAP; hypercapnia; hypoxemia; noninvasive ventilation; sleep apnea.

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Conflict of interest statement

All authors have seen and approved this manuscript. This study was funded by Instituto de Salud Carlos III (Fondo de Investigaciones Sanitarias, Ministerio de Sanidad y Consumo) PI050402, Spanish Respiratory Foundation 2005 (FEPAR), and Air Liquide Spain. The sponsors and funders of the study had no involvement or any influence in study design; in the collection, analysis, and interpretation of data; in the writing of the manuscript; and in the decision to submit the manuscript for publication. The corresponding author (J.F.M.) confirms that he had full access to all the data in the study and he had the final responsibility for the decision to submit for publication. The authors report no conflicts of interest.

Figures

Figure 1
Figure 1. Study flowchart.
Flow chart of the study protocol. Of 375 selected patients, 56 were excluded and 319 were randomized: 221 in the severe OSA trial and 98 in the nonsevere OSA trial. Of this 319, 73 were excluded because of inadequate echocardiogram. Of the remaining 246, 122 had and 124 did not have PH. Of the 122 with PH, 87 had severe OSA and 35 had nonsevere OSA who were included in the subgroup analysis, severe OSA and nonsevere OSA, respectively. Of the 124 without PH, 80 had severe OSA and 44 had nonsevere OSA who were included in the subgroup analysis, severe OSA and nonsevere OSA, respectively. Therefore, the severe OSA subgroup had 167 patients and nonsevere OSA had 79 patients. ECHO = transthoracic echocardiogram, OSA = obstructive sleep apnea, PH = pulmonary hypertension, RCT = randomized controlled trial, sPAP = systolic pulmonary artery pressure.
See this image and copyright information in PMC

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