Risk factors associated with pulmonary hypertension in obesity hypoventilation syndrome

J Clin Sleep Med. 2021 Nov 11. doi: 10.5664/jcsm.9760. Online ahead of print.


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 ≤0.10 were defined as potential risk factors and were grouped by theoretical pathogenic mechanisms in several adjusted models. Similar analysis was carried out for the two OHS phenotypes, with and without severe concomitant obstructive sleep apnea (OSA).

Results: Of 246 patients with OHS, 122 (50%) had echocardiographic evidence of PH defined as systolic pulmonary artery pressure ≥40 mmHg. Lower levels of awake PaO2 and higher body mass index (BMI) were independent risk factors in the multivariate model, with a negative and positive adjusted linear association, respectively (adjusted odds ratio 0.96; 95% CI 0.93 to 0.98; p = 0.003 for PaO2, and 1.07; 95% CI 1.03 to 1.12; p = 0.001 for BMI). In separate analyses, BMI and PaO2 were independent risk factors in the severe OSA phenotype, whereas BMI and peak in-flow velocity in early (E)/late diastole (A) ratio were independent risk factors in the non-severe OSA 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 trials registration: Registry: Clinicaltrial.gov; Identifier: NCT01405976.

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

Associated data

  • ClinicalTrials.gov/NCT01405976