Juan F Masa1,2,3, Iván D Benítez2,4, Shahrokh Javaheri5, Maria Victoria Mogollon6, Maria Á Sánchez-Quiroga2,3,7, Francisco J Gomez de Terreros1,2,3, Jaime Corral1,2,3, Rocio Gallego1,2,3, Auxiliadora Romero2,8, Candela Caballero-Eraso2,8, Estrella Ordax-Carbajo2,9, María F Troncoso2,10, Mónica González11, Soledad López-Martín12, José M Marin2,13, Sergi Martí2,14, Trinidad Díaz-Cambriles2,15, Eusebi Chiner16, Carlos Egea2,17, Javier Barca3,18, Ferrán Barbé2,4, Babak Mokhlesi19. 1. Respiratory Department, San Pedro de Alcántara Hospital, Cáceres, Spain. 2. CIBER de Enfermedades Respiratorias (CIBERES), Madrid, Spain. 3. Instituto Universitario de Investigación Biosanitaria de Extremadura (INUBE). 4. Institut de Recerca Biomédica de Lleida (IRBLLEIDA), Lleida, Spain. 5. Division of Pulmonary and Sleep Medicine, Bethesda North Hospital, Cincinnati, Ohio. 6. Cardiology Department, San Pedro de Alcántara Hospital, Cáceres, Spain. 7. Respiratory Department, Virgen del Puerto Hospital, Plasencia, Cáceres, Spain. 8. Unidad Médico-Quirúrgica de Enfermedades Respiratorias, Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío, Sevilla, Spain. 9. Respiratory Department, University Hospital, Burgos, Spain. 10. Respiratory Department, IIS Fundación Jiménez Díaz, Madrid, Spain. 11. Respiratory Department, Valdecilla Hospital, Santander, Spain. 12. Respiratory Department, Gregorio Marañón Hospital, Madrid, Spain. 13. Respiratory Department, Miguel Servet Hospital, Zaragoza, Spain. 14. Respiratory Department, Vall d'Hebron Hospital, Barcelona, Spain. 15. Respiratory Department, Doce de Octubre Hospital, Madrid, Spain. 16. Respiratory Department, San Juan Hospital, Alicante, Spain. 17. Respiratory Department, Alava University Hospital IRB, Vitoria, Spain. 18. Nursing Department, Extremadura University, Cáceres, Spain. 19. Medicine/Pulmonary and Critical Care, University of Chicago, Illinois.
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.
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.
Authors: Juan F Masa; Babak Mokhlesi; Iván Benítez; Francisco Javier Gomez de Terreros; Maria Ángeles Sánchez-Quiroga; Auxiliadora Romero; Candela Caballero-Eraso; Joaquin Terán-Santos; Maria Luz Alonso-Álvarez; Maria F Troncoso; Mónica González; Soledad López-Martín; José M Marin; Sergi Martí; Trinidad Díaz-Cambriles; Eusebi Chiner; Carlos Egea; Javier Barca; Francisco-José Vázquez-Polo; Miguel A Negrín; María Martel-Escobar; Ferran Barbe; Jaime Corral Journal: Lancet Date: 2019-03-29 Impact factor: 79.321
Authors: Francisco García-Río; Myriam Calle; Felip Burgos; Pere Casan; Félix Del Campo; Juan B Galdiz; Jordi Giner; Nicolás González-Mangado; Francisco Ortega; Luis Puente Maestu Journal: Arch Bronconeumol Date: 2013-05-28 Impact factor: 4.872
Authors: P Lévy; J-L Pépin; C Arnaud; R Tamisier; J-C Borel; M Dematteis; D Godin-Ribuot; C Ribuot Journal: Eur Respir J Date: 2008-10 Impact factor: 16.671
Authors: Juan F Masa; Antonio Jiménez; Joaquín Durán; Francisco Capote; Carmen Monasterio; Mercedes Mayos; Joaquín Terán; Lourdes Hernández; Ferrán Barbé; Andrés Maimó; Manuela Rubio; José M Montserrat Journal: Am J Respir Crit Care Med Date: 2004-07-28 Impact factor: 21.405
Authors: L A De Backer; W G Vos; R Salgado; J W De Backer; A Devolder; S L Verhulst; R Claes; P R Germonpré; W A De Backer Journal: Int J Chron Obstruct Pulmon Dis Date: 2011-11-28
Authors: Juan F Masa; Jaime Corral; Candela Caballero; Emilia Barrot; Joaquin Terán-Santos; Maria L Alonso-Álvarez; Teresa Gomez-Garcia; Mónica González; Soledad López-Martín; Pilar De Lucas; José M Marin; Sergi Marti; Trinidad Díaz-Cambriles; Eusebi Chiner; Carlos Egea; Erika Miranda; Babak Mokhlesi; Estefanía García-Ledesma; M-Ángeles Sánchez-Quiroga; Estrella Ordax; Nicolás González-Mangado; Maria F Troncoso; Maria-Ángeles Martinez-Martinez; Olga Cantalejo; Elena Ojeda; Santiago J Carrizo; Begoña Gallego; Mercedes Pallero; M Antonia Ramón; Josefa Díaz-de-Atauri; Jesús Muñoz-Méndez; Cristina Senent; Jose N Sancho-Chust; Francisco J Ribas-Solís; Auxiliadora Romero; José M Benítez; Jesús Sanchez-Gómez; Rafael Golpe; Ana Santiago-Recuerda; Silvia Gomez; Mónica Bengoa Journal: Thorax Date: 2016-07-12 Impact factor: 9.139