Unraveling the molecular mechanisms of OSA-related cardiovascular event recurrence: A post hoc analysis from the ISAACC study

• Andrea Zapater ^[7] ; Lucía Pinilla ^[7] ; Esther Gracia Lavedan ^[1] ; Adriano Targa ^[1] ; Gerard Torres ^[1] ; Olga Mínguez ^[8] ; Lydia Pascual ^[8] ; Anunciación Cortijo ^[8] ; Dolores Martínez ^[8] ; Ivan David Benítez ^[1] ; Maria Coronada García Hidalgo ^[1] ; Jordi De Batlle ^[1] ; Jorge Abad ^[1] ; Joaquín Duran Cantolla ^[1] ; Amaia Urrutia ^[9] ; Olga Mediano ^[1] ; María José Masdeu ^[1] ; Estrella Ordax Carbajo ^[2] ; Juan Fernando Masa ^[1] ; Mónica De la Peña ^[3] ; Mercè Mayos ^[1] ; Ramon Coloma ^[10] ; Josep María Montserrat ^[1] ; Eusebi Chiner ^[4] ; Alejandra Roncero ^[5] ; David Sanz Rubio ^[6] ; Ferran Barbé ^[1] ; Manuel Sánchez de la Torre ^[1]
  1. [1] Centro de Investigacion Biomedica en Red de Enfermedades Respiratorias

     Centro de Investigacion Biomedica en Red de Enfermedades Respiratorias

     Madrid, España

     
  2. [2] Complejo Asistencial Universitario de Burgos

     Complejo Asistencial Universitario de Burgos

     Burgos, España

     
  3. [3] Hospital Universitario Son Espases

     Hospital Universitario Son Espases

     Palma de Mallorca, España

     
  4. [4] Hospital Universitario San Juan de Alicante

     Hospital Universitario San Juan de Alicante

     Alicante, España

     
  5. [5] Hospital San Pedro

     Hospital San Pedro

     Logroño, España

     
  6. [6] Hospital Miguel Servet

     Hospital Miguel Servet

     Zaragoza, España

     
  7. [7] Group of Precision Medicine in Chronic Diseases, University Hospital Arnau de Vilanova and Santa María, IRBLleida, Lleida, Spain
  8. [8] Translation Research in Respiratory Medicine, Hospital Universitari Arnau de Vilanova-Santa Maria, IRBLleida, Lleida, Spain
  9. [9] Servicio Neurologia, Hospital Universitario Cruces, Bizkaia, Spain
  10. [10] Respiratory Department, Hospital General Universitario de Albacete, Spain

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• Localización: Archivos de bronconeumología: Organo oficial de la Sociedad Española de Neumología y Cirugía Torácica SEPAR y la Asociación Latinoamericana de Tórax ( ALAT ), ISSN 0300-2896, Vol. 61, Nº. 4, 2025, págs. 203-211
• Idioma: inglés
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• Resumen

  • 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.