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Randomized Controlled Trial
. 2025 Apr;61(4):203-211.
doi: 10.1016/j.arbres.2024.09.008. Epub 2024 Oct 9.

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

[Article in English, Spanish]
Andrea Zapater  1 , Lucía Pinilla  1 , Esther Gracia-Lavedan  2 , Adriano Targa  2 , Gerard Torres  2 , Olga Mínguez  3 , Lydia Pascual  3 , Anunciación Cortijo  3 , Dolores Martínez  3 , Ivan David Benítez  2 , Maria Coronada García-Hidalgo  2 , Jordi De Batlle  2 , Jorge Abad  4 , Joaquín Duran-Cantolla  5 , Amaia Urrutia  6 , Olga Mediano  7 , María José Masdeu  8 , Estrella Ordax-Carbajo  9 , Juan Fernando Masa  10 , Mónica De la Peña  11 , Mercè Mayos  12 , Ramon Coloma  13 , Josep María Montserrat  14 , Eusebi Chiner  15 , Alejandra Roncero  16 , David Sanz-Rubio  17 , Ferran Barbé  2 , Manuel Sánchez-de-la-Torre  18 ; Spanish Sleep Network
Affiliations
Randomized Controlled Trial

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

[Article in English, Spanish]
Andrea Zapater et al. Arch Bronconeumol. 2025 Apr.

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: Acute coronary syndrome; Biomarkers; Cardiovascular disease; Molecular pathways; Obstructive sleep apnea; Proteomics.

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