Unraveling the Molecular Mechanisms of OSA-Related Cardiovascular Event Recurrence: A Post Hoc Analysis From the ISAACC Study

Zapater, Andrea; Pinilla, Lucía; Gracia-Lavedan, Esther; Targa, Adriano; Torres, Gerard; Mínguez, Olga; Pascual, Lydia; Cortijo, Anunciación; Martínez, Dolores; Benítez, Ivan David; García-Hidalgo, Maria Coronada; De Batlle, Jordi; Abad, Jorge; Duran-Cantolla, Joaquín; Urrutia, Amaia; Mediano, Olga; Masdeu, María José; Ordax-Carbajo, Estrella; Masa, Juan Fernando; De la Peña, Mónica; Mayos, Mercè; Coloma, Ramon; Montserrat, Josep María; Chiner, Eusebi; Roncero, Alejandra; Sanz-Rubio, David; Barbé, Ferran; Sánchez-de-la-Torre, Manuel

doi:10.1016/j.arbres.2024.09.008

Archivos de Bronconeumología

ISSN: 0300-2896

Archivos de Bronconeumologia is an international journal that publishes original studies whose content is based upon results of research initiatives dealing with several aspects of respiratory medicine including epidemiology, respiratory physiology, pathophysiology of respiratory diseases, clinical management, thoracic surgery, pediatric lung diseases, respiratory critical care, respiratory allergy and translational research. Other types of articles such as editorials, reviews, and different types of letters are also published in the journal. Additionally, the journal expresses the voice of the following scientific societies: the Spanish Respiratory Society of Pneumology and Thoracic Surgery (SEPAR; https://www.separ.es/), the Latin American Thoracic Society (ALAT; https://alatorax.org/), and the Iberian American Association of Thoracic Surgery (AIACT; http://www.aiatorax.com/).

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Andrea Zapatera,b,1, Lucía Pinillaa,b,1, Esther Gracia-Lavedanb,c, Adriano Targab,c, Gerard Torresb,c, Olga Mínguezc, Lydia Pascualc, Anunciación Cortijoc, Dolores Martínezc, Ivan David Benítezb,c, Maria Coronada García-Hidalgob,c, Jordi De Batlleb,c, Jorge Abadb,d, Joaquín Duran-Cantollab,e, Amaia Urrutiaf, Olga Medianob,g, María José Masdeub,h, Estrella Ordax-Carbajoi, Juan Fernando Masab,j, Mónica De la Peñak..., Mercè Mayosb,l, Ramon Colomam, Josep María Montserratb,n, Eusebi Chinero, Alejandra Roncerop, David Sanz-Rubioq, Ferran Barbéb,c, Manuel Sánchez-de-la-Torreb,r,

Corresponding author

sanchezdelatorre@gmail.com

Corresponding author.

, on behalf of the Spanish Sleep Network Ver más

a Group of Precision Medicine in Chronic Diseases, University Hospital Arnau de Vilanova and Santa María, IRBLleida, Lleida, Spain

b Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Madrid, Spain

c Translation Research in Respiratory Medicine, Hospital Universitari Arnau de Vilanova-Santa Maria, IRBLleida, Lleida, Spain

d Respiratory Department, Hospital Universitari Germans Trias I Pujol, Badalona, Barcelona, Spain

e Servicio de Investigación OSI, Hospital Universitario Araba, IIS Bioaraba, Vitoria, Álava, Spain

f Servicio Neurologia, Hospital Universitario Cruces, Bizkaia, Spain

g Respiratory Department, Hospital Universitario de Guadalajara, Guadalajara, Spain

h Respiratory and Sleep Department, Hospital Universitari Parc Taulí, Institut Investigació i Innovació Parc Taulí (I3PT), Universitat Autònoma de Barcelona, Sabadell, Spain

i Respiratory Department, Hospital Universitario de Burgos, Burgos, Spain

j Respiratory Department, Hospital San Pedro Alcántara, Cáceres, Spain

k Clinic Analysis and Respiratory Services, Hospital Universitari Son Espases, Institut de investigació sanitaria de Palma (IdisPa), Palma de Mallorca, Spain

l Sleep Unit, Department of Respiratory Medicine, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain

m Respiratory Department, Hospital General Universitario de Albacete, Spain

n Respiratory Department, Hospital Clinic, Barcelona, Spain

o Respiratory Department, Hospital Universitari Sant Joan d’Alacant, Alicante, Spain

p Unidad Multidisciplinar del Sueño, Servicio de Neumología, Hospital San Pedro, Logroño, Spain

q Precision Medicine in Respiratory Diseases (PRES) Group, Unidad de Investigación Traslacional, Instituto de Investigación Sanitaria de Aragón-IISA, Hospital Universitario Miguel Servet, Zaragoza, Spain

r Group of Precision Medicine in Chronic Diseases, Hospital Nacional de Parapléjicos, IDISCAM, Department of Nursing, Physiotherapy and Occupational Therapy, Faculty of Physiotherapy and Nursing, University of Castilla-La Mancha, Toledo, Spain

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Table 1. Baseline Characteristics of ACS Patients With Recurrent CVEs According to OSA Condition (Non-OSA vs. Untreated Severe OSA).

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Abstract

Rationale

Although obstructive sleep apnea (OSA) is a prevalent condition among patients with acute coronary syndrome (ACS), the impact of OSA on cardiovascular event (CVE) recurrence is not homogeneous. We previously defined a specific phenotype of first-ACS patients without previous cardiovascular disease who are at increased risk of OSA-related CVE recurrence. However, the pathobiological mechanisms whereby OSA leads to adverse cardiovascular outcomes in this singular ACS phenotype remain to be investigated.

Objective

To characterize the molecular pathways that relate OSA with CVE recurrence.

Methods

This post hoc analysis of the ISAACC study (NCT01335087) included subjects without previous cardiovascular disease who were hospitalized for a first ACS and developed a recurrent CVE during the follow-up. Patients underwent respiratory polygraphy and fasting blood extraction during hospitalization. Two study groups were established on the basis of the apnea–hypopnea index (AHI): untreated severe OSA (AHI≥30events/h) and non-OSA (AHI<15events/h) groups. Proteomic profiling analysis included 276 cardiovascular and inflammatory-related plasma proteins via Olink® technology.

Results

Proteomics was performed in 58 patients (77.6% male, median [p25;p75] age 58.0 [51.2;65.8] years, and median BMI 28.6 [25.8;31.2]kg/m2). Thirty patients had severe OSA, and 28 subjects were considered non-OSA controls. A total of 24 plasma proteins were differentially expressed between the groups. Among these proteins, 18 were significantly associated with OSA severity parameters derived from respiratory polygraphy. Further bioinformatic analyses of OSA-related proteins revealed their involvement in several molecular pathways, mostly related to immune function, cell signaling, and inflammatory processes.

Conclusion

A specific proteomic profile related to OSA presence and severity was identified in the plasma of ACS patients who developed recurrent CVEs. This analysis suggests the activation of key OSA-mediated molecular pathways with potential implications for cardiovascular prognosis.

Keywords:

Obstructive sleep apnea

Acute coronary syndrome

Proteomics

Biomarkers

Molecular pathways

Cardiovascular disease

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