Pinilla Lucía, Benítez Iván D, Gracia-Lavedan Esther, Torres Gerard, Mínguez Olga, Vaca Rafaela, Jové Mariona, Sol Joaquim, Pamplona Reinald, Barbé Ferran, Sánchez-de-la-Torre Manuel
Precision Medicine in Chronic Diseases Group, Respiratory Department, University Hospital Arnau de Vilanova and Santa María, Department of Nursing and Physiotherapy, Faculty of Nursing and Physiotherapy, University of Lleida, IRBLleida, 25198 Lleida, Spain.
Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III (ISCIII), 28029 Madrid, Spain.
Antioxidants (Basel). 2023 Nov 27;12(12):2047. doi: 10.3390/antiox12122047.
A non-dipping blood pressure (BP) pattern, which is frequently present in patients with obstructive sleep apnea (OSA), confers high cardiovascular risk. The mechanisms connecting these two conditions remain unclear. In the present study we performed a comprehensive analysis of the blood metabolipidome that aims to provide new insights into the molecular link between OSA and the dysregulation of circadian BP rhythmicity. This was an observational prospective longitudinal study involving adults with suspected OSA who were subjected to full polysomnography (PSG). Patients with an apnea-hypopnea index ≥ 5 events/h were included. Fasting plasma samples were obtained the morning after PSG. Based on the dipping ratio (DR; ratio of night/day BP values) measured via 24 h ambulatory BP monitoring, two groups were established: dippers (DR ≤ 0.9) and non-dippers (DR > 0.9). Treatment recommendations for OSA followed the clinical guidelines. Untargeted metabolomic and lipidomic analyses were performed in plasma samples via liquid chromatography-tandem mass spectrometry. Non-dipper patients represented 53.7% of the cohort (88/164 patients). A set of 31 metabolic species and 13 lipidic species were differentially detected between OSA patients who present a physiologic nocturnal BP decrease and those with abnormal BP dipping. Among the 44 differentially abundant plasma compounds, 25 were putatively identified, notably glycerophospholipids, glycolipids, sterols, and fatty acid derivates. Multivariate analysis defined a specific metabotype of non-dipping BP, which showed a significant dose-response relationship with PSG parameters of OSA severity, and with BP dipping changes after 6 months of OSA treatment with continuous positive airway pressure (CPAP). Bioinformatic analyses revealed that the identified metabolipidomic profile was found to be implicated in multiple systemic biological pathways, with potential physiopathologic implications for the circadian control of BP among individuals with OSA.
非勺型血压模式常见于阻塞性睡眠呼吸暂停（OSA）患者中，具有较高的心血管风险。这两种情况之间的联系机制尚不清楚。在本研究中，我们对血液代谢脂质组进行了全面分析，旨在为OSA与昼夜血压节律失调之间的分子联系提供新的见解。这是一项观察性前瞻性纵向研究，纳入了疑似OSA的成年人，并对其进行了全夜多导睡眠图（PSG）检查。纳入呼吸暂停低通气指数≥5次/小时的患者。在PSG检查后的早晨采集空腹血浆样本。根据通过24小时动态血压监测测得的勺型率（DR；夜间/白天血压值的比值），将患者分为两组：勺型者（DR≤0.9）和非勺型者（DR>0.9）。OSA的治疗建议遵循临床指南。通过液相色谱-串联质谱法对血浆样本进行非靶向代谢组学和脂质组学分析。非勺型患者占队列的53.7%（164例患者中的88例）。在生理性夜间血压下降的OSA患者和血压勺型异常的患者之间，差异检测到一组31种代谢物和13种脂质。在44种差异丰富的血浆化合物中，25种被初步鉴定，主要是甘油磷脂、糖脂、固醇和脂肪酸衍生物。多变量分析定义了一种特定的非勺型血压代谢型，它与OSA严重程度的PSG参数以及持续气道正压通气（CPAP）治疗OSA 6个月后的血压勺型变化呈显著的剂量反应关系。生物信息学分析表明，所鉴定的代谢脂质组谱涉及多个全身生物学途径，对OSA患者的血压昼夜控制具有潜在的病理生理学意义。
