Andrea Zapater, Lucía Pinilla, Esther Gracia-Lavedan, Adriano Targa, Gerard Torres, Olga Mínguez, Lydia Pascual, Anunciación Cortijo, Dolores Martínez, Ivan David Benítez, Maria Coronada García-Hidalgo, Jordi De Batlle, Jorge Abad, Joaquín Duran-Cantolla, Amaia Urrutia, Olga Mediano, María José Masdeu, Estrella Ordax-Carbajo, Juan Fernando Masa, Mónica De la Peña, Mercè Mayos, Ramon Coloma, Josep María Montserrat, Eusebi Chiner, Alejandra Roncero, David Sanz-Rubio, Ferran Barbé, Manuel Sánchez-de-la-Torre
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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.</p><p><strong>Objective: </strong>To characterize the molecular pathways that relate OSA with CVE recurrence.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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/m<sup>2</sup>). 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.</p><p><strong>Conclusion: </strong>A specific proteomic profile related to OSA presence and severity was identified in the plasma of ACS patients who developed recurrent CVEs. 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引用次数: 0
摘要
理由：虽然阻塞性睡眠呼吸暂停（OSA）在急性冠状动脉综合征（ACS）患者中很普遍，但 OSA 对心血管事件（CVE）复发的影响却不尽相同。我们曾定义了一种特殊的表型，即既往无心血管疾病的首发冠状动脉综合征患者与 OSA 相关的 CVE 复发风险增加。然而，OSA导致这一特殊ACS表型的不良心血管后果的病理生物学机制仍有待研究：目的：描述 OSA 与 CVE 复发相关的分子途径：这项对ISAACC研究（NCT01335087）的事后分析纳入了既往无心血管疾病、因首次ACS住院并在随访期间复发CVE的受试者。患者在住院期间接受了呼吸测谎和空腹抽血。根据呼吸暂停-低通气指数（AHI）分为两组：未经治疗的严重 OSA（AHI≥30events/h）和非 OSA（AHIResults：对 58 名患者（77.6% 为男性，中位 [p25;p75] 年龄 58.0 [51.2;65.8] 岁，中位体重指数 28.6 [25.8;31.2] kg/m2）进行了蛋白质组学研究。30 名患者患有严重 OSA，28 名患者被视为非 OSA 对照组。各组间共有 24 种血浆蛋白质的表达存在差异。在这些蛋白质中，有 18 种与呼吸测谎仪得出的 OSA 严重程度参数显著相关。对 OSA 相关蛋白质的进一步生物信息学分析表明，这些蛋白质参与了多个分子通路，其中大部分与免疫功能、细胞信号传导和炎症过程有关：结论：在复发性CVE的ACS患者血浆中发现了与OSA的存在和严重程度相关的特异性蛋白质组谱。该分析表明，OSA介导的关键分子通路被激活，对心血管预后有潜在影响。
Unraveling the Molecular Mechanisms of OSA-Related Cardiovascular Event Recurrence: A Post Hoc Analysis From the ISAACC Study.
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.
期刊介绍：
Archivos de Bronconeumologia is a scientific journal that specializes in publishing prospective original research articles focusing on various aspects of respiratory diseases, including epidemiology, pathophysiology, clinical practice, surgery, and basic investigation. Additionally, the journal features other types of articles such as reviews, editorials, special articles of interest to the society and editorial board, scientific letters, letters to the editor, and clinical images. Published monthly, the journal comprises 12 regular issues along with occasional supplements containing articles from different sections.
All manuscripts submitted to the journal undergo rigorous evaluation by the editors and are subjected to expert peer review. The editorial team, led by the Editor and/or an Associate Editor, manages the peer-review process. Archivos de Bronconeumologia is published monthly in English, facilitating broad dissemination of the latest research findings in the field.
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