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Xue J, Allaband C, Zuffa S, Poulsen O, Meadows J, Zhou D, Dorrestein PC, Knight R, Haddad GG. Gut microbiota and derived metabolites mediate obstructive sleep apnea induced atherosclerosis. Gut Microbes 2025; 17:2474142. [PMID: 40025767 PMCID: PMC11881840 DOI: 10.1080/19490976.2025.2474142] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/04/2024] [Revised: 02/03/2025] [Accepted: 02/25/2025] [Indexed: 03/04/2025] Open
Abstract
Obstructive sleep apnea (OSA) is characterized by intermittent hypoxia/hypercapnia (IHC), affects predominantly obese individuals, and increases atherosclerosis risk. Since we and others have implicated gut microbiota and metabolites in atherogenesis, we dissected their contributions to OSA-induced atherosclerosis. Atherosclerotic lesions were compared between conventionally-reared specific pathogen free (SPF) and germ-free (GF) Apoe-/- mice following a high fat high cholesterol diet (HFHC), with and without IHC conditions. The fecal microbiota and metabolome were profiled using 16S rRNA gene amplicon sequencing and untargeted tandem mass spectrometry (LC-MS/MS) respectively. Phenotypic data showed that HFHC significantly increased atherosclerosis as compared to regular chow (RC) in both aorta and pulmonary artery (PA) of SPF mice. IHC exacerbated lesions in addition to HFHC. Differential abundance analysis of gut microbiota identified an enrichment of Akkermansiaceae and a depletion of Muribaculaceae (formerly S24-7) family members in the HFHC-IHC group. LC-MS/MS showed a dysregulation of bile acid profiles with taurocholic acid, taurodeoxycholic acid, and 12-ketodeoxycholic acid enriched in the HFHC-IHC group, long-chain N-acyl amides, and phosphatidylcholines. Interestingly, GF Apoe-/- mice markedly reduced atherosclerotic formation relative to SPF Apoe-/- mice in the aorta under HFHC/IHC conditions. In contrast, microbial colonization did not show a significant impact on the atherosclerotic progression in PA. In summary, this research demonstrated that (1) IHC acts cooperatively with HFHC to induce atherosclerosis; (2) gut microbiota modulate atherogenesis, induced by HFHC/IHC, in the aorta not in PA; (3) different analytical methods suggest that a specific imbalance between Akkermansiaceae and Muribaculaceae bacterial families mediate OSA-induced atherosclerosis; and (4) derived bile acids, such as deoxycholic acid and lithocholic acid, regulate atherosclerosis in OSA. The knowledge obtained provides novel insights into the potential therapeutic approaches to prevent and treat OSA-induced atherosclerosis.
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MESH Headings
- Animals
- Gastrointestinal Microbiome/physiology
- Atherosclerosis/etiology
- Atherosclerosis/microbiology
- Atherosclerosis/metabolism
- Sleep Apnea, Obstructive/complications
- Sleep Apnea, Obstructive/microbiology
- Sleep Apnea, Obstructive/metabolism
- Mice
- Male
- Bacteria/classification
- Bacteria/genetics
- Bacteria/metabolism
- Bacteria/isolation & purification
- Diet, High-Fat/adverse effects
- Feces/microbiology
- Mice, Inbred C57BL
- RNA, Ribosomal, 16S/genetics
- Bile Acids and Salts/metabolism
- Metabolome
- Specific Pathogen-Free Organisms
- Disease Models, Animal
- Tandem Mass Spectrometry
- Mice, Knockout, ApoE
- Apolipoproteins E/genetics
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Affiliation(s)
- Jin Xue
- Department of Pediatrics, University of California San Diego, La Jolla, CA, USA
| | - Celeste Allaband
- Department of Pediatrics, University of California San Diego, La Jolla, CA, USA
| | - Simone Zuffa
- Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA, USA
- Collaborative Mass Spectrometry Innovation Center, University of California San Diego, San Diego, CA, USA
| | - Orit Poulsen
- Department of Pediatrics, University of California San Diego, La Jolla, CA, USA
| | - Jason Meadows
- Department of Pediatrics, University of California San Diego, La Jolla, CA, USA
| | - Dan Zhou
- Department of Pediatrics, University of California San Diego, La Jolla, CA, USA
| | - Pieter C. Dorrestein
- Department of Pediatrics, University of California San Diego, La Jolla, CA, USA
- Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA, USA
- Collaborative Mass Spectrometry Innovation Center, University of California San Diego, San Diego, CA, USA
| | - Rob Knight
- Department of Pediatrics, University of California San Diego, La Jolla, CA, USA
- Center for Microbiome Innovation, University of California, San Diego, La Jolla, CA, USA
- Department of Computer Science and Engineering, University of California, San Diego, La Jolla, CA, USA
| | - Gabriel G. Haddad
- Department of Pediatrics, University of California San Diego, La Jolla, CA, USA
- Department of Neuroscience, University of California San Diego, La Jolla, CA, USA
- The Division of Respiratory Medicine, Rady Children’s Hospital, San Diego, CA, USA
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Zhao Y, Lv R, He Y, Dong N, Wang X, Pu J, Yu Q. The miR-21-5p/DUSP8/MAPK signaling pathway mediates inflammation and apoptosis in vascular endothelial cells induced by intermittent hypoxia and contributes to the protective effects of N-acetylcysteine. Eur J Pharmacol 2025; 997:177462. [PMID: 40058751 DOI: 10.1016/j.ejphar.2025.177462] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2024] [Revised: 02/27/2025] [Accepted: 03/04/2025] [Indexed: 03/15/2025]
Abstract
Obstructive sleep apnoea hypopnea syndrome (OSAHS) is a sleep disorder associated with significant cardiovascular complications, characterized by intermittent hypoxia (IH). IH causes endothelial dysfunction, an early event in cardiovascular disease. We investigated the role of dual-specificity phosphatase 8 (DUSP8), a key negative regulator of the mitogen-activated protein kinase (MAPK) signalling pathway, in IH-induced endothelial cell damage, and the therapeutic effects of N-acetylcysteine (NAC) by establishing IH models in human umbilical vein endothelial cells and C57BL/6 mice. DUSP8 and MAPK signalling pathway-related proteins were analysed by western blotting, and DUSP8 mRNA and miR-21-5p expression was assessed by RT-qPCR. Inflammatory cytokines were detected by an enzyme-linked immunosorbent assay, apoptosis-related proteins were analysed by western blotting, and apoptosis was assessed using flow cytometry. IH stimulation induced inflammation and apoptosis in endothelial cells, downregulated DUSP8 expression, and upregulated the phosphorylation of key molecules involved in the MAPK signalling pathway. However, DUSP8 overexpression alleviated IH-induced inflammation and apoptosis in endothelial cells and reduced the phosphorylation of key molecules in the MAPK signalling pathway. Bioinformatic analysis and dual-luciferase reporter assays confirmed that DUSP8 is a direct target of miR-21-5p. DUSP8 overexpression effectively reversed the damage caused by miR-21-5p upregulation under IH conditions. Furthermore, in cell and animal models of IH, NAC demonstrated protective effects against inflammation, apoptosis, and oxidative stress through a mechanism linked to the miR-21-5p/DUSP8/MAPK signalling pathway. Overall, this study elucidated the protective role of DUSP8 against IH-induced endothelial injury and confirmed the potential of NAC as a therapeutic agent for OSAHS-related diseases.
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Affiliation(s)
- Yan Zhao
- The First School of Clinical Medicine, Lanzhou University, Lanzhou, 730000, China
| | - Renjun Lv
- The First School of Clinical Medicine, Lanzhou University, Lanzhou, 730000, China
| | - Yao He
- The First School of Clinical Medicine, Lanzhou University, Lanzhou, 730000, China
| | - Na Dong
- The First School of Clinical Medicine, Lanzhou University, Lanzhou, 730000, China
| | - Xiao Wang
- The First School of Clinical Medicine, Lanzhou University, Lanzhou, 730000, China
| | - Jiayuan Pu
- Department of Pulmonary and Critical Care Medicine, The First Hospital of Lanzhou University, Lanzhou, 730000, China
| | - Qin Yu
- The First School of Clinical Medicine, Lanzhou University, Lanzhou, 730000, China; Department of Pulmonary and Critical Care Medicine, The First Hospital of Lanzhou University, Lanzhou, 730000, China.
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Sanz-Rubio D, Martín-Burriel I, Rodríguez J, Marín-Oto M, Khalyfa A, Sánchez-de-la-Torre M, Gozal D, Marin JM. Circulating Exosomal MicroRNAs and Subclinical Atherosclerosis in Obstructive Sleep Apnea. Arch Bronconeumol 2025; 61:235-238. [PMID: 39741042 DOI: 10.1016/j.arbres.2024.12.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2024] [Revised: 12/11/2024] [Accepted: 12/12/2024] [Indexed: 01/02/2025]
Affiliation(s)
- David Sanz-Rubio
- Precision Medicine in Respiratory Diseases Group, Hospital Universitario Miguel Servet, Instituto de Investigación Sanitaria de Aragón (IISAragón), Zaragoza, Spain.
| | - Inmaculada Martín-Burriel
- Laboratorio de Genética Bioquímica (LAGENBIO), Instituto Agroalimentario de Aragón IA2 (UNIZAR-CITA), Instituto de Investigación Sanitaria de Aragón (IISAragón), Universidad de Zaragoza, Zaragoza, Spain; Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNed), Madrid, Spain
| | - Jorge Rodríguez
- Precision Medicine in Respiratory Diseases Group, Hospital Universitario Miguel Servet, Instituto de Investigación Sanitaria de Aragón (IISAragón), Zaragoza, Spain
| | - Marta Marín-Oto
- Precision Medicine in Respiratory Diseases Group, Hospital Universitario Miguel Servet, Instituto de Investigación Sanitaria de Aragón (IISAragón), Zaragoza, Spain
| | - Abdelnaby Khalyfa
- Department of Biomedical Sciences, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV, USA
| | - Manuel Sánchez-de-la-Torre
- 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; Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERes), Madrid, Spain
| | - David Gozal
- Department of Pediatrics, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV, USA
| | - Jose M Marin
- Precision Medicine in Respiratory Diseases Group, Hospital Universitario Miguel Servet, Instituto de Investigación Sanitaria de Aragón (IISAragón), Zaragoza, Spain; Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERes), Madrid, Spain; Respiratory Service, Hospital Universitario Miguel Servet, University of Zaragoza, Zaragoza, Spain
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Akinmoju OD, Olatunji G, Kokori E, Ogieuhi IJ, Babalola AE, Obi ES, Anthony CS, Toluwanibukun OG, Akingbola A, Alao AE, Boluwatife AG, Venkatraman A, Babar A, Aderinto N. Comparative Efficacy of Continuous Positive Airway Pressure and Antihypertensive Medications in Obstructive Sleep Apnea-Related Hypertension: A Narrative Review. High Blood Press Cardiovasc Prev 2025; 32:127-137. [PMID: 39718706 DOI: 10.1007/s40292-024-00691-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2024] [Accepted: 10/23/2024] [Indexed: 12/25/2024] Open
Abstract
INTRODUCTION Obstructive sleep apnea (OSA) presents a significant global health concern, affecting a substantial portion of the population, particularly among young and middle-aged adults. AIM This review aims to assess the efficacy of continuous positive airway pressure (CPAP) compared to antihypertensive medications in managing OSA-related hypertension. METHODS A comprehensive literature search was conducted across multiple databases, yielding studies published from 2000 to March 2024 that investigated CPAP, antihypertensives, or their combination therapy in OSA patients. Six definitive studies were analyzed, including two randomized controlled trials (RCTs), one randomized double-blind placebo-controlled crossover trial, one placebo-controlled trial, one open-label multicenter trial, and one longitudinal cohort study. These studies comprised 939 participants, with intervention durations ranging from four weeks to six months. RESULTS Analysis of CPAP monotherapy revealed variable efficacy, with some studies demonstrating significant reductions in 24-hour mean blood pressure and diastolic pressure, while others reported non-significant changes. CPAP therapy combined with antihypertensives showed additive effects, particularly in reducing office blood pressure measurements. Antihypertensive medications, such as valsartan, exhibited superior efficacy in reducing blood pressure compared to CPAP alone. Factors influencing therapy effectiveness included CPAP compliance, patient characteristics, and coexisting comorbidities. Patients with good CPAP adherence experienced greater reductions in blood pressure. The duration of exposure to OSA and the type of hypertension also impacted the therapy response. CONCLUSION While CPAP and antihypertensive medications offer significant benefits in managing hypertension among OSA patients, challenges such as CPAP intolerance and medication side effects exist. Personalized treatment considering individual patient factors is crucial for optimal management.
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Affiliation(s)
| | - Gbolahan Olatunji
- Department of Medicine and Surgery, University of Ilorin, Ilorin, Nigeria
| | - Emmanuel Kokori
- Department of Medicine and Surgery, University of Ilorin, Ilorin, Nigeria
| | | | | | | | | | | | | | | | | | | | | | - Nicholas Aderinto
- Department of Medicine and Surgery, Ladoke Akintola University of Technology, Ogbomoso, Nigeria
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Huang Z, Zhao Q, Zhao Z, Thomas RJ, Duan A, Li X, Zhang S, Gao L, An C, Wang Y, Li S, Wang Q, Luo Q, Liu Z, Consensus Group, National Cardiovascular Disease Expert Committee, Sleep Medicine Professional Committee Cardiovascular Group of the Chinese Medical Doctor Association, Elderly Sleep Disorders and Cardiopulmonary Vascular Group of the Chinese Society of Gerontology and Geriatrics. Chinese consensus report on the assessment and management of obstructive sleep apnea in patients with cardiovascular disease: 2024 edition. Sleep Med 2025; 126:248-259. [PMID: 39721361 DOI: 10.1016/j.sleep.2024.12.019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/17/2024] [Revised: 12/09/2024] [Accepted: 12/14/2024] [Indexed: 12/28/2024]
Abstract
As cardiovascular disease (CVD) incidence and mortality rates continue to rise in China, the importance of identifying and managing CVD risk factors grows. Obstructive sleep apnea (OSA) is a prevalent sleep-related breathing disorder, affecting an estimated 936 million individuals aged 30-69 worldwide, with China leading globally with about 176 million affected. Increasing research indicates a close association between OSA and the onset and progression of various CVD, significantly affecting outcomes. However, OSA has long been underrecognized and undertreated in CVD clinical practice. To address this gap, a multidisciplinary expert panel developed evidence-based recommendations using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology and the Delphi process. This consensus provides 17 recommendations on core clinical issues such as screening, diagnosis, treatment, and follow-up of CVD patients with OSA, aiming to standardize care and improve patient outcomes. The recommendations were informed by current evidence-based research and extensive expert consensus discussions. This approach seeks to support clinical decision-making, improve the quality of care, and address the unique challenges of managing OSA in Chinese CVD patients.
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Affiliation(s)
- Zhihua Huang
- Center for Respiratory and Pulmonary Vascular Diseases, Department of Cardiology, Fuwai Hospital, National Clinical Research Center for Cardiovascular Diseases, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Qing Zhao
- Center for Respiratory and Pulmonary Vascular Diseases, Department of Cardiology, Fuwai Hospital, National Clinical Research Center for Cardiovascular Diseases, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Zhihui Zhao
- Center for Respiratory and Pulmonary Vascular Diseases, Department of Cardiology, Fuwai Hospital, National Clinical Research Center for Cardiovascular Diseases, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Robert Joseph Thomas
- Department of Medicine, Division of Pulmonary, Critical Care & Sleep Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, United States
| | - Anqi Duan
- Center for Respiratory and Pulmonary Vascular Diseases, Department of Cardiology, Fuwai Hospital, National Clinical Research Center for Cardiovascular Diseases, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Xin Li
- Center for Respiratory and Pulmonary Vascular Diseases, Department of Cardiology, Fuwai Hospital, National Clinical Research Center for Cardiovascular Diseases, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Sicheng Zhang
- Center for Respiratory and Pulmonary Vascular Diseases, Department of Cardiology, Fuwai Hospital, National Clinical Research Center for Cardiovascular Diseases, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Luyang Gao
- Center for Respiratory and Pulmonary Vascular Diseases, Department of Cardiology, Fuwai Hospital, National Clinical Research Center for Cardiovascular Diseases, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Chenhong An
- Center for Respiratory and Pulmonary Vascular Diseases, Department of Cardiology, Fuwai Hospital, National Clinical Research Center for Cardiovascular Diseases, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yijia Wang
- Center for Respiratory and Pulmonary Vascular Diseases, Department of Cardiology, Fuwai Hospital, National Clinical Research Center for Cardiovascular Diseases, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Sicong Li
- Center for Respiratory and Pulmonary Vascular Diseases, Department of Cardiology, Fuwai Hospital, National Clinical Research Center for Cardiovascular Diseases, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Qi Wang
- Center for Respiratory and Pulmonary Vascular Diseases, Department of Cardiology, Fuwai Hospital, National Clinical Research Center for Cardiovascular Diseases, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Qin Luo
- Center for Respiratory and Pulmonary Vascular Diseases, Department of Cardiology, Fuwai Hospital, National Clinical Research Center for Cardiovascular Diseases, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
| | - Zhihong Liu
- Center for Respiratory and Pulmonary Vascular Diseases, Department of Cardiology, Fuwai Hospital, National Clinical Research Center for Cardiovascular Diseases, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
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Liu W, Zhang L, Liao W, Liu H, Liang W, Yan J, Huang Y, Jiang T, Wang Q, Zhang C. Unveiling the molecular and cellular links between obstructive sleep apnea-hypopnea syndrome and vascular aging. Chin Med J (Engl) 2025; 138:155-171. [PMID: 39647991 PMCID: PMC11745861 DOI: 10.1097/cm9.0000000000003352] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2024] [Indexed: 12/10/2024] Open
Abstract
ABSTRACT Vascular aging (VA) is a common etiology of various chronic diseases and represents a major public health concern. Intermittent hypoxia (IH) associated with obstructive sleep apnea-hypopnea syndrome (OSAHS) is a primary pathological and physiological driver of OSAHS-induced systemic complications. A substantial proportion of OSAHS patients, estimated to be between 40% and 80%, have comorbidities such as hypertension, heart failure, coronary artery disease, pulmonary hypertension, atrial fibrillation, aneurysm, and stroke, all of which are closely associated with VA. This review examines the molecular and cellular features common to both OSAHS and VA, highlighting decreased melatonin secretion, impaired autophagy, increased apoptosis, increased inflammation and pyroptosis, increased oxidative stress, accelerated telomere shortening, accelerated stem cell depletion, metabolic disorders, imbalanced protein homeostasis, epigenetic alterations, and dysregulated neurohormonal signaling. The accumulation and combination of these features may underlie the pathophysiological link between OSAHS and VA, but the exact mechanisms by which OSAHS affects VA may require further investigation. Taken together, these findings suggest that OSAHS may serve as a novel risk factor for VA and related vascular disorders, and that targeting these features may offer therapeutic potential to mitigate the vascular risks associated with OSAHS.
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Affiliation(s)
- Wei Liu
- Department of Geriatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095 Jiefang Avenue, Wuhan, Hubei 430030, China
- Key Laboratory of Vascular Aging, Ministry of Education, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095 Jiefang Avenue, Wuhan, Hubei 430030, China
| | - Le Zhang
- Institute of Gerontology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095 Jiefang Avenue, Wuhan, Hubei 430030, China
| | - Wenhui Liao
- Department of Geriatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095 Jiefang Avenue, Wuhan, Hubei 430030, China
- Key Laboratory of Vascular Aging, Ministry of Education, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095 Jiefang Avenue, Wuhan, Hubei 430030, China
| | - Huiguo Liu
- Department of Respiratory and Critical Care Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095 Jiefang Avenue, Wuhan, Hubei 430030, China
| | - Wukaiyang Liang
- Department of Geriatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095 Jiefang Avenue, Wuhan, Hubei 430030, China
- Key Laboratory of Vascular Aging, Ministry of Education, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095 Jiefang Avenue, Wuhan, Hubei 430030, China
| | - Jinhua Yan
- Department of Geriatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095 Jiefang Avenue, Wuhan, Hubei 430030, China
- Key Laboratory of Vascular Aging, Ministry of Education, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095 Jiefang Avenue, Wuhan, Hubei 430030, China
| | - Yi Huang
- Department of Geriatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095 Jiefang Avenue, Wuhan, Hubei 430030, China
- Key Laboratory of Vascular Aging, Ministry of Education, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095 Jiefang Avenue, Wuhan, Hubei 430030, China
| | - Tao Jiang
- Department of Geriatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095 Jiefang Avenue, Wuhan, Hubei 430030, China
- Key Laboratory of Vascular Aging, Ministry of Education, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095 Jiefang Avenue, Wuhan, Hubei 430030, China
| | - Qian Wang
- Department of Geriatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095 Jiefang Avenue, Wuhan, Hubei 430030, China
- Key Laboratory of Vascular Aging, Ministry of Education, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095 Jiefang Avenue, Wuhan, Hubei 430030, China
| | - Cuntai Zhang
- Department of Geriatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095 Jiefang Avenue, Wuhan, Hubei 430030, China
- Key Laboratory of Vascular Aging, Ministry of Education, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095 Jiefang Avenue, Wuhan, Hubei 430030, China
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Wang L, Wang Y, Jiao T, Xu L, Ji E, Tapu SR, Liu Y, Li J. Effects of continuous positive airway pressure treatment on arterial stiffness and inflammatory factors in patients with coronary heart disease complicated with obstructive sleep apnea. J Cardiothorac Surg 2025; 20:59. [PMID: 39799348 PMCID: PMC11724610 DOI: 10.1186/s13019-024-03252-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2024] [Accepted: 12/24/2024] [Indexed: 01/15/2025] Open
Abstract
BACKGROUND Continuous Positive Airway Pressure (CPAP) treatment brings more benefits than risks to most coronary heart disease (CHD) patients with obstructive sleep apnea (OSA). However, the pathophysiological mechanism by which CPAP treatment improves the prognosis of patients with CHD and OSA remains unclear. The purpose of this study was to clarify whether CPAP can improve arterial stiffness and inflammatory factor levels in CHD patients with OSA, and to further improve prognosis. METHOD 59 patients with coronary heart disease complicated by moderate to severe sleep apnea were divided into a CPAP treatment group (CPAP + coronary heart disease standard treatment) and a control group (only coronary heart disease standard treatment). Peripheral blood test reports were collected and pulse wave velocity (PWV) measurements were performed for each patient at the beginning, 3 months, and 6 months of treatment. RESULTS After 6 months of treatment, the CPAP group showed more significant improvement in the levels of inflammatory factors such as white blood cell (WBC), neutrophil (N), C-reactive protein (CRP), interleukin-6 (IL-6), procalcitonin (PCT), and PWV than the control group. CONCLUSION After active treatment with CPAP, arterial stiffness and inflammatory cytokine levels in patients with coronary heart disease and OSA improved. This association should be given more attention in clinical practice, and sleep apnea should be actively treated.
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Affiliation(s)
- Liang Wang
- Department of Cardiology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Yuanqi Wang
- School of Medicine, Tongji University, Shanghai, China
| | - Tiantian Jiao
- School of Medicine, Tongji University, Shanghai, China
| | - Linghao Xu
- Department of Cardiology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Endong Ji
- Department of Emergency and Critical Care, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | | | - Yehong Liu
- Department of Cardiology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Jiming Li
- Department of Cardiology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China.
- Department of Cardiology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, 200092, China.
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Avcı D, Avcı A, Ertas R, Ozyurt K, Ulaş Y, Çetinkaya A, Mustafa A. Exploring the Potential Link: Atherosclerosis and Chronic Spontaneous Urticaria: Analyzing Lipid-Related Atherosclerosis Markers in 203 Patients at a Specialized Urticaria Outpatient Clinic in a Tertiary Center. Niger J Clin Pract 2025; 28:57-69. [PMID: 40326937 DOI: 10.4103/njcp.njcp_321_24] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2024] [Accepted: 12/19/2024] [Indexed: 05/07/2025]
Abstract
BACKGROUND This study investigated the relationship between Chronic spontaneous urticaria and atherogenic dyslipidemia. METHODS The study retrospectively screened 203 patients diagnosed with CSU and 182 healthy controls between January 2017 and January 2024. We compared the weight of the atherogenic component in the cholesterol components of patients with CSU. The same comparisons were made in patients and control groups when those with total lipid levels below ≤ 200 mg/dL were selected. RESULTS Atherogenicity markers such as Atherogenic index of plasma (AIP) (p<0.001), remnant lipoproteins (p<0.001), non-HDL-C (p=0.031), and non-HDL to HDL-C ratio (p=0.043) values were higher in the CSU group compared to the healthy control group. While this situation was similar in the female gender, statistical significance remained only for AIP (p=0.004) and remnant lipoproteins (p=0.043) among these parameters in males. While there was statistical significance for AIP (p=0.004) and remnant lipoproteins (p=0.043) in patients with total cholesterol levels ≤ 200 mg/dL, no significant differences were detected for the markers non-HDL-C (p=0.545) and non-HDL-C to HDL-C (p=0.292). CONCLUSIONS Atherogenic lipids may be markers that may able to differentiate patients with the potential to develop CSU.
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Affiliation(s)
- D Avcı
- Department of Internal Medicine, Kayseri Medical Faculty, Sağlık Bilimleri University, Kayseri, Turkey
| | - A Avcı
- Department of Dermatology and Venereology, Kayseri Medical Faculty, Sağlık Bilimleri University, Kayseri, Turkey
| | - R Ertas
- Department of Dermatology and Venereology, Medical Palace Hospital, Kayseri, Turkey
| | - K Ozyurt
- Department of Dermatology and Venereology, Acıbadem Kayseri Hospital, Kayseri, Turkey
| | - Y Ulaş
- Department of Dermatology and Venereology, Kayseri Medical Faculty, Sağlık Bilimleri University, Kayseri, Turkey
| | - A Çetinkaya
- Department of Internal Medicine, Kayseri Medical Faculty, Sağlık Bilimleri University, Kayseri, Turkey
| | - A Mustafa
- Department of Dermatology and Venereology, Memorial Ataşehir Hospital, Kayseri, Turkey
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9
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Park KM, Wi JH, Kim J. The association between small vessel disease and obstructive sleep apnea: a peak width of skeletonized mean diffusivity-based study. Sleep Breath 2024; 29:29. [PMID: 39612020 DOI: 10.1007/s11325-024-03196-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2024] [Revised: 09/13/2024] [Accepted: 10/07/2024] [Indexed: 11/30/2024]
Abstract
PURPOSE Peak width of skeletonized mean diffusivity (PSMD) is a novel marker of small vessel disease in the brain. This study aimed to investigate the association between small vessel disease and obstructive sleep apnea (OSA) using PSMD. METHODS We enrolled patients with OSA and age- and sex-matched healthy controls, and performed diffusion tensor imaging (DTI) using a 3-tesla MRI scanner in them. We calculated the PSMD based on DTI in several steps, including preprocessing, skeletonization, application of a custom mask, and histogram analysis using the FSL program. We compared the PSMD between patients with OSA and healthy controls and investigated the correlation between PSMD and clinical factors. RESULTS Thirty-nine patients with OSA (apnea-hypopnea index > 5; mean = 20.5) and 48 healthy controls were enrolled. The PSMD was significantly higher in patients with OSA than that in the healthy controls (2.521 vs. 2.320 × 10- 4 mm2/s, p = 0.013). In addition, PSMD positively correlated with age (r = 0.512, p < 0.001) and body mass index (r = 0.472, p = 0.002). However, PSMD was not associated with polysomnographic measurements. CONCLUSIONS The mean PSMD is higher in patients with OSA than that in healthy controls, indicating a white matter injury due to small-vessel disease in patients with OSA. Our study highlights the importance of actively diagnosing and treating OSA. In addition, PSMD can be used to determine the relationship between sleep disorders and small vessel disease.
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Affiliation(s)
- Kang Min Park
- Department of Neurology, Haeundae Paik Hospital, Inje University College of Medicine, Busan, Korea
| | - Jin-Hong Wi
- Department of Thoracic and Cardiovascular Surgery, Busan Paik Hospital, Inje University College of Medicine, Busan, Korea
| | - Jinseung Kim
- Department of Family Medicine, Busan Paik Hospital, Inje University College of Medicine, 75, Bokji-ro, Busanjin-gu, Busan, 47392, Republic of Korea.
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10
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Martins AVV, Krul LT, Drager LF. Sleep Duration, Genetics, and Atherosclerosis: Challenges and Opportunities. Arq Bras Cardiol 2024; 121:e20240593. [PMID: 39607099 PMCID: PMC11634226 DOI: 10.36660/abc.20240593] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2024] [Revised: 09/13/2024] [Accepted: 09/13/2024] [Indexed: 11/29/2024] Open
Affiliation(s)
- Ana Vitoria Vitoreti Martins
- Hospital das Clínicas da Faculdade de Medicina da USPInstituto do CoraçãoUnidade de HipertensãoSão PauloSPBrasilUnidade de Hipertensão - Instituto do Coração (InCor), Hospital das Clínicas da Faculdade de Medicina da USP, São Paulo, SP – Brasil
| | - Larissa T. Krul
- Hospital das Clínicas da Faculdade de Medicina da USPInstituto do CoraçãoUnidade de HipertensãoSão PauloSPBrasilUnidade de Hipertensão - Instituto do Coração (InCor), Hospital das Clínicas da Faculdade de Medicina da USP, São Paulo, SP – Brasil
| | - Luciano F. Drager
- Hospital das Clínicas da Faculdade de Medicina da USPInstituto do CoraçãoUnidade de HipertensãoSão PauloSPBrasilUnidade de Hipertensão - Instituto do Coração (InCor), Hospital das Clínicas da Faculdade de Medicina da USP, São Paulo, SP – Brasil
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11
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Xue J, Allaband C, Zuffa S, Poulsen O, Meadows J, Zhou D, Dorrestein PC, Knight R, Haddad GG. Gut Microbiota and Derived Metabolites Mediate Obstructive Sleep Apnea Induced Atherosclerosis. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2024:2024.11.18.624205. [PMID: 39605650 PMCID: PMC11601605 DOI: 10.1101/2024.11.18.624205] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/29/2024]
Abstract
Background Obstructive sleep apnea (OSA) is characterized by intermittent hypoxia/hypercapnia (IHC), affects predominantly obese individuals, and increases atherosclerosis risk. Since we and others have implicated gut microbiota and metabolites in atherogenesis, we dissected their contributions to OSA-induced atherosclerosis. Results Atherosclerotic lesions were compared between conventionally-reared specific pathogen free (SPF) and germ-free (GF) ApoE -/- mice following a high fat high cholesterol diet (HFHC), with and without IHC conditions. The fecal microbiota and metabolome were profiled using 16S rRNA gene amplicon sequencing and untargeted tandem mass spectrometry (LC-MS/MS) respectively. Phenotypic data showed that HFHC significantly increased atherosclerosis as compared to regular chow (RC) in both aorta and pulmonary artery (PA) of SPF mice. IHC exacerbated lesions in addition to HFHC. Differential abundance analysis of gut microbiota identified an enrichment of Akkermansiaceae and a depletion of Muribaculaceae (formerly S24-7) family members in the HFHC-IHC group. LC-MS/MS showed a dysregulation of bile acid profiles with taurocholic acid, taurodeoxycholic acid, and 12-ketodeoxycholic acid enriched in the HFHC-IHC group, long-chain N-acyl amides, and phosphatidylcholines. Interestingly, GF ApoE -/- mice markedly reduced atherosclerotic formation relative to SPF ApoE -/- mice in the aorta under HFHC/IHC conditions. In contrast, microbial colonization did not show a significant impact on the atherosclerotic progression in PA. Conclusions In summary, this research demonstrated that (1) IHC acts cooperatively with HFHC to induce atherosclerosis; (2) gut microbiota modulate atherogenesis, induced by HFHC/IHC, in the aorta not in PA; (3) different analytical methods suggest that a specific imbalance between Akkermansiaceae and Muribaculaceae bacterial families mediate OSA-induced atherosclerosis; and (4) derived bile acids, such as deoxycholic acid and lithocholic acid, regulate atherosclerosis in OSA. The knowledge obtained provides novel insights into the potential therapeutic approaches to prevent and treat OSA-induced atherosclerosis.
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12
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Zhang Z, Ai H, Yan M, Zheng W, Yan Y, Wang X, Fan J, Que B, Li S, Wang G, Gong W, Nie S. Prognostic effect of obstructive sleep apnea in acute coronary syndrome patients with heart failure. Respir Med 2024; 234:107814. [PMID: 39307479 DOI: 10.1016/j.rmed.2024.107814] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/14/2024] [Revised: 08/28/2024] [Accepted: 09/20/2024] [Indexed: 09/27/2024]
Abstract
BACKGROUND AND OBJECTIVE Acute coronary syndrome (ACS), heart failure (HF) and obstructive sleep apnea (OSA) often overlap and interact, the impact of OSA on ACS patients with HF remains unclear. The study sought to comprehensively evaluate the effects of the interaction between OSA and HF on long-term cardiovascular outcomes in ACS patients. METHODS Between June 2015 and January 2020, patients hospitalized for ACS were prospectively enrolled and underwent portable sleep monitoring after clinically stabilization. OSA was defined as an apnea hypopnea index ≥15 events/h. HF was defined using medical records. The primary endpoint was major adverse cardiovascular and cerebrovascular event (MACCE), including death, myocardial infarction, stroke, ischemia-driven revascularization, and hospitalization for unstable angina. RESULTS Among all 1927 included patients, 214 (11.1 %) had HF, and 1014 (52.6 %) had OSA. For 2.9 years (1.5, 3.6 years) follow-up, OSA was independently associated with the risk of MACCE in HF patients (adjusted hazard ratio [HR], 2.11; 95%CI, 1.16-3.84; P = 0.014), but not in those without HF (adjusted HR, 1.15; 95%CI, 0.92-1.45; P = 0.228). Further analysis showed OSA exerted more prognostic effect in HF patients with preserved eject fraction (adjusted HR, 2.45; 95 % CI, 1.11-5.41; P = 0.027) than those with reduced eject fraction (adjusted HR, 1.62; 95 % CI, 0.63-4.20; P = 0.319). CONCLUSIONS In the settings of ACS, OSA was independently associated with poor prognosis in patients with concomitant HF especially those with persevered ejection fraction. Screening and treatment for OSA are highly recommended in ACS patients with HF. CLINICAL TRIAL REGISTRATION URL: www.clinicaltrails.gov; Unique Identifier: NCT03362385.
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Affiliation(s)
- Zekun Zhang
- Center for Coronary Artery Disease, Division of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China; National Clinical Research Center for Cardiovascular Diseases, Beijing, China
| | - Hui Ai
- Center for Coronary Artery Disease, Division of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China; National Clinical Research Center for Cardiovascular Diseases, Beijing, China
| | - Mengwen Yan
- Department of Cardiology, China-Japan Friendship Hospital, Beijing, China
| | - Wen Zheng
- Center for Coronary Artery Disease, Division of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China; National Clinical Research Center for Cardiovascular Diseases, Beijing, China
| | - Yan Yan
- Center for Coronary Artery Disease, Division of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China; National Clinical Research Center for Cardiovascular Diseases, Beijing, China
| | - Xiao Wang
- Center for Coronary Artery Disease, Division of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China; National Clinical Research Center for Cardiovascular Diseases, Beijing, China
| | - Jingyao Fan
- Center for Coronary Artery Disease, Division of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China; National Clinical Research Center for Cardiovascular Diseases, Beijing, China
| | - Bin Que
- Center for Coronary Artery Disease, Division of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China; National Clinical Research Center for Cardiovascular Diseases, Beijing, China
| | - Siyi Li
- Center for Coronary Artery Disease, Division of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China; National Clinical Research Center for Cardiovascular Diseases, Beijing, China
| | - Ge Wang
- Center for Coronary Artery Disease, Division of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China; National Clinical Research Center for Cardiovascular Diseases, Beijing, China
| | - Wei Gong
- Center for Coronary Artery Disease, Division of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China; National Clinical Research Center for Cardiovascular Diseases, Beijing, China; Department of Cardiology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, 1 Dahua Road, Dongdan, Dongcheng District, Beijing, 100730, China.
| | - Shaoping Nie
- Center for Coronary Artery Disease, Division of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China; National Clinical Research Center for Cardiovascular Diseases, Beijing, China.
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13
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Braga PGS, Giampá SQDC. Good night's sleep, good arterial health: are there differences between men and women living with obstructive sleep apnoea? J Physiol 2024; 602:5973-5974. [PMID: 38551969 DOI: 10.1113/jp286370] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/01/2024] Open
Affiliation(s)
- Pedro Gabriel Senger Braga
- Laboratory of Cellular and Molecular Exercise Physiology, School of Physical Education and Sports of University of Sao Paulo, Brazil
- Clinica Pro-Coracao, Sao Paulo, Brazil
| | - Sara Quaglia de Campos Giampá
- Unidade de Hipertensão, Instituto do Coração (InCor), Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil
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14
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Goulet N, Marcoux C, Bourgon V, Morin R, Mauger JF, Amaratunga R, Imbeault P. Biological sex-related differences in the postprandial triglyceride response to intermittent hypoxaemia in young adults: a randomized crossover trial. J Physiol 2024; 602:5817-5834. [PMID: 38285004 DOI: 10.1113/jp285430] [Citation(s) in RCA: 5] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2023] [Accepted: 01/10/2024] [Indexed: 01/30/2024] Open
Abstract
Obstructive sleep apnoea is characterized by chronic intermittent hypoxaemia and is independently associated with an increased risk of metabolic comorbidities (e.g. type II diabetes and ischaemic heart disease). These comorbidities could be attributable to hypoxaemia-induced alterations in blood lipid profiles. However, it remains unclear whether intermittent hypoxaemia alters triglyceridaemia differently between biological sexes. Therefore, we used a randomized crossover design to examine whether 6 h of moderate intermittent hypoxaemia (15 hypoxaemic cycles/h, 85% oxyhaemoglobin saturation) alters plasma triglyceride levels differently between men and women after a high-fat meal. Relative to men, women displayed lower levels of total triglycerides, in addition to denser triglyceride-rich lipoprotein triglycerides (TRL-TG; mainly very low-density lipoprotein triglycerides and chylomicron remnant triglycerides) and buoyant TRL-TG (mainly chylomicron triglycerides) during normoxia (ambient air) and intermittent hypoxaemia (sex × time: all P ≤ 0.008). Intermittent hypoxaemia led to higher triglyceride levels (condition: all P ≤ 0.016); however, this effect was observed only in men (sex × condition: all P ≤ 0.002). Compared with normoxia, glucose levels were higher in men and lower in women during intermittent hypoxaemia (sex × condition: P < 0.001). The different postprandial responses between biological sexes occurred despite similar reductions in mean oxyhaemoglobin saturation and similar elevations in insulin levels, non-esterified fatty acid levels and mean heart rate (sex × condition: all P ≥ 0.185). These results support growing evidence showing that intermittent hypoxaemia impacts men and women differently, and they might help to explain biological sex-related discrepancies in the rate of certain comorbidities associated with intermittent hypoxaemia. KEY POINTS: Intermittent hypoxaemia is a key characteristic of obstructive sleep apnoea and alters lipid metabolism in multiple tissues, resulting in increased circulating triglyceride levels, an important risk factor for cardiometabolic diseases. Circulating triglyceride levels are regulated differently between biological sexes, with women typically displaying much lower fasting and postprandial triglyceride levels than men, partly explaining why women of all ages experience lower mortality rates from cardiometabolic diseases. In this study, healthy young men and women consumed a high-fat meal and were then exposed to 6 h of intermittent hypoxaemia or ambient air. We show that postprandial triglyceride levels are significantly lower in women compared with men and that intermittent hypoxaemia leads to higher postprandial triglyceride levels in men only. These results might help us to understand better why women living with obstructive sleep apnoea experience lower rates of cardiometabolic diseases (e.g. type II diabetes and ischaemic heart disease) than men living with obstructive sleep apnoea.
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Affiliation(s)
- Nicholas Goulet
- Behavioural and Metabolic Research Unit, School of Human Kinetics, Faculty of Health Sciences, University of Ottawa, Ottawa, ON, Canada
| | - Caroline Marcoux
- Behavioural and Metabolic Research Unit, School of Human Kinetics, Faculty of Health Sciences, University of Ottawa, Ottawa, ON, Canada
| | - Vincent Bourgon
- Laboratoire du Sommeil, Département de psychoéducation et de psychologie, Université du Québec en Outaouais, Gatineau, QC, Canada
| | - Renée Morin
- Behavioural and Metabolic Research Unit, School of Human Kinetics, Faculty of Health Sciences, University of Ottawa, Ottawa, ON, Canada
| | - Jean-François Mauger
- Behavioural and Metabolic Research Unit, School of Human Kinetics, Faculty of Health Sciences, University of Ottawa, Ottawa, ON, Canada
| | - Ruwan Amaratunga
- Institut du Savoir Montfort, Montfort Hospital, Ottawa, ON, Canada
| | - Pascal Imbeault
- Behavioural and Metabolic Research Unit, School of Human Kinetics, Faculty of Health Sciences, University of Ottawa, Ottawa, ON, Canada
- Institut du Savoir Montfort, Montfort Hospital, Ottawa, ON, Canada
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15
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Massimini M, Corbetta M, Sanchez-Vives MV, Andrillon T, Deco G, Rosanova M, Sarasso S. Sleep-like cortical dynamics during wakefulness and their network effects following brain injury. Nat Commun 2024; 15:7207. [PMID: 39174560 PMCID: PMC11341729 DOI: 10.1038/s41467-024-51586-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2023] [Accepted: 08/07/2024] [Indexed: 08/24/2024] Open
Abstract
By connecting old and recent notions, different spatial scales, and research domains, we introduce a novel framework on the consequences of brain injury focusing on a key role of slow waves. We argue that the long-standing finding of EEG slow waves after brain injury reflects the intrusion of sleep-like cortical dynamics during wakefulness; we illustrate how these dynamics are generated and how they can lead to functional network disruption and behavioral impairment. Finally, we outline a scenario whereby post-injury slow waves can be modulated to reawaken parts of the brain that have fallen asleep to optimize rehabilitation strategies and promote recovery.
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Grants
- The authors thank Dr Ezequiel Mikulan, Dr Silvia Casarotto, Dr Andrea Pigorini, Dr Simone Russo, and Dr Pilleriin Sikka for their help and comments on the manuscript draft and illustrations. This work was financially supported by the following entities: ERC-2022-SYG Grant number 101071900 Neurological Mechanisms of Injury and Sleep-like Cellular Dynamics (NEMESIS); Italian National Recovery and Resilience Plan (NRRP), M4C2, funded by the European Union - NextGenerationEU (Project IR0000011, CUP B51E22000150006, “EBRAINS-Italy”); European Union’s Horizon 2020 Framework Program for Research and Innovation under the Specific Grant Agreement No.945539 (Human Brain Project SGA3); Tiny Blue Dot Foundation; Canadian Institute for Advanced Research (CIFAR), Canada; Italian Ministry for Universities and Research (PRIN 2022); Fondazione Regionale per la Ricerca Biomedica (Regione Lombardia), Project ERAPERMED2019–101, GA 779282; CORTICOMOD PID2020-112947RB-I00 financed by MCIN/ AEI /10.13039/501100011033; Fondazione Cassa di Risparmio di Padova e Rovigo (CARIPARO) Grant Agreement number 55403; Ministry of Health, Italy (RF-2008 -12366899) Brain connectivity measured with high-density electroencephalography: a novel neurodiagnostic tool for stroke- NEUROCONN; BIAL foundation grant (Grant Agreement number 361/18); H2020 European School of Network Neuroscience (euSNN); H2020 Visionary Nature Based Actions For Heath, Wellbeing & Resilience in Cities (VARCITIES); Ministry of Health Italy (RF-2019-12369300): Eye-movement dynamics during free viewing as biomarker for assessment of visuospatial functions and for closed-loop rehabilitation in stroke (EYEMOVINSTROKE).
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Affiliation(s)
- Marcello Massimini
- Department of Biomedical and Clinical Sciences, University of Milan, Milan, Italy.
- IRCCS Fondazione Don Carlo Gnocchi ONLUS, Milan, Italy.
| | - Maurizio Corbetta
- Department of Neuroscience and Padova Neuroscience Center (PNC), University of Padova, Padova, Italy
- Veneto Institute of Molecular Medicine (VIMM), Padova, Italy
| | - Maria V Sanchez-Vives
- Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain
- Institució Catalana de la Recerca i Estudis Avançats (ICREA), Barcelona, Spain
| | - Thomas Andrillon
- Sorbonne Université, Institut du Cerveau - Paris Brain Institute - ICM, Mov'it team, Inserm, CNRS, Paris, France
- Monash Centre for Consciousness and Contemplative Studies, Faculty of Arts, Monash University, Melbourne, VIC, Australia
| | - Gustavo Deco
- Institució Catalana de la Recerca i Estudis Avançats (ICREA), Barcelona, Spain
- Department of Information and Communication Technologies, Universitat Pompeu Fabra, Center for Brain and Cognition, Computational Neuroscience Group, Barcelona, Spain
| | - Mario Rosanova
- Department of Biomedical and Clinical Sciences, University of Milan, Milan, Italy
| | - Simone Sarasso
- Department of Biomedical and Clinical Sciences, University of Milan, Milan, Italy
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16
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Kerget B, Afşin DE, Laloglu E. Evaluation of serum salusin-α and β levels in patients with obstructive sleep apnea. Biomark Med 2024; 18:603-610. [PMID: 38982740 PMCID: PMC11370929 DOI: 10.1080/17520363.2024.2366151] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2024] [Accepted: 05/20/2024] [Indexed: 07/11/2024] Open
Abstract
Aim: Salusin-α and salusin-β peptides are crucial in the development of cardiovascular diseases like coronary artery disease (CAD). This study compared serum levels of these peptides in patients with obstructive sleep apnea (OSA), those with both OSA and CAD.Materials & methods: Patients without OSA were included in Group 1, those with OSA alone comprised Group 2, and those with OSA and CAD were in Group 3.Results: Salusin-α level was significantly higher in controls than in Groups 2 and 3, while salusin-β levels were significantly higher in Groups 2 and 3 compared with the control group.Conclusion: Salusin-α and -β levels may be parameters that can guide the diagnosis of OSA in patients with a consistent clinical history.
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Affiliation(s)
- Buğra Kerget
- Depertment of Pulmonary Diseases, Ataturk University School of Medicine, Yakutiye, Erzurum, Turkey
| | - Dursun Erol Afşin
- Depertment of Pulmonary Diseases, Health Sciences University Erzurum Regional Education and Research Hospital, Erzurum, Turkey
| | - Esra Laloglu
- Depertment of Biochamistry, Ataturk University School of Medicine, Yakutiye, Erzurum, Turkey
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17
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Gami N, Shukla K, Patel I, Gandhi NM. Epidemiological Study of Sleep Apnea Prevalence and Associated Risk Factors in a Large Patient Population. JOURNAL OF PHARMACY AND BIOALLIED SCIENCES 2024; 16:S2721-S2723. [PMID: 39346172 PMCID: PMC11426764 DOI: 10.4103/jpbs.jpbs_426_24] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2024] [Revised: 04/13/2024] [Accepted: 04/18/2024] [Indexed: 10/01/2024] Open
Abstract
Background Significant morbidity and death are linked to sleep apnea (SP), a prevalent sleep disease. For successful management, it is essential to comprehend its prevalence and the risk factors that are linked with it. The purpose of this study was to look at the prevalence of SP in a large patient group that was visiting a tertiary care facility and to discover risk variables that are connected with it. Methods 500 volunteers were gathered from a tertiary care center to participate in cross-sectional research. Polysomnography, clinical evaluations, and standardized questionnaires were utilized to diagnose SP and gather pertinent information. A statistical study was conducted to evaluate the correlation between different risk factors and SP. Results 35% of people had SP, with men between the ages of 40 and 60 having a greater frequency. It has been determined that smoking, obesity, and high blood pressure are important risk factors for SP. Compared to those with mild or moderate SP, individuals with severe SP had greater rates of smoking, hypertension, and obesity (BMI > 30). Conclusion This study emphasizes how common SP is in tertiary care settings and how it is linked to smoking, obesity, and hypertension. Improving patient outcomes and lessening the impact of SP need early identification and management techniques that address these modifiable risk factors.
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Affiliation(s)
- Nihar Gami
- MBBS, Gujarat Cancer Society Medical College Hospital and Research Center, Ahmedabad, Gujarat, India
| | - Krutarth Shukla
- MBBS, Gujarat Cancer Society Medical College Hospital and Research Center, Ahmedabad, Gujarat, India
| | - Ishan Patel
- MBBS, Smt. Nathiba Hargovandas Lakhmichand Municipal Medical College, Ahmedabad, Gujarat, India
| | - Nayan Manish Gandhi
- MBBS, Gujarat Cancer Society Medical College Hospital and Research Center, Ahmedabad, Gujarat, India
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18
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Maniaci A, Lavalle S, Parisi FM, Barbanti M, Cocuzza S, Iannella G, Magliulo G, Pace A, Lentini M, Masiello E, La Via L. Impact of Obstructive Sleep Apnea and Sympathetic Nervous System on Cardiac Health: A Comprehensive Review. J Cardiovasc Dev Dis 2024; 11:204. [PMID: 39057624 PMCID: PMC11277108 DOI: 10.3390/jcdd11070204] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2024] [Revised: 06/22/2024] [Accepted: 06/26/2024] [Indexed: 07/28/2024] Open
Abstract
A prevalent condition linked to an elevated risk of cardiovascular disease is sleep apnea. This review examines the connections between cardiac risk, the sympathetic nervous system, and sleep apnea. The increased risk of hypertension, arrhythmias, myocardial infarction, and heart failure was highlighted in the pathophysiology of sleep apnea and its effect on sympathetic activation. It is also important to consider potential processes such as oxidative stress, inflammation, endothelial dysfunction, and autonomic imbalance that may relate sleep apnea-induced sympathetic activation to cardiac risk. With implications for creating innovative diagnostic and treatment approaches to lessen the cardiovascular effects of sleep apnea, the goal of this investigation is to improve the understanding of the intricate link between sympathetic activity, cardiac risk, and sleep apnea. This study aimed to clarify the complex relationship between cardiovascular health and sleep apnea by synthesizing the available research and highlighting the crucial role played by the sympathetic nervous system in moderating this relationship. Our thorough investigation may have important therapeutic ramifications that will direct the creation of focused therapies to enhance cardiovascular outcomes in sleep apnea sufferers.
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Affiliation(s)
- Antonino Maniaci
- Department of Medicine and Surgery, University of Enna “Kore”, 94100 Enna, Italy; (A.M.); (M.B.)
| | - Salvatore Lavalle
- Department of Medicine and Surgery, University of Enna “Kore”, 94100 Enna, Italy; (A.M.); (M.B.)
| | - Federica Maria Parisi
- Department of Medical, Surgical Sciences and Advanced Technologies “GF Ingrassia” ENT Section, University of Catania, 95123 Catania, Italy; (F.M.P.); (S.C.)
| | - Marco Barbanti
- Department of Medicine and Surgery, University of Enna “Kore”, 94100 Enna, Italy; (A.M.); (M.B.)
| | - Salvatore Cocuzza
- Department of Medical, Surgical Sciences and Advanced Technologies “GF Ingrassia” ENT Section, University of Catania, 95123 Catania, Italy; (F.M.P.); (S.C.)
| | - Giannicola Iannella
- Otorhinolaryngology Department, Sapienza University of Rome, Policlinico Umberto I, Viale del Policlinico, 00161 Rome, Italy; (G.I.); (G.M.); (A.P.)
| | - Giuseppe Magliulo
- Otorhinolaryngology Department, Sapienza University of Rome, Policlinico Umberto I, Viale del Policlinico, 00161 Rome, Italy; (G.I.); (G.M.); (A.P.)
| | - Annalisa Pace
- Otorhinolaryngology Department, Sapienza University of Rome, Policlinico Umberto I, Viale del Policlinico, 00161 Rome, Italy; (G.I.); (G.M.); (A.P.)
| | - Mario Lentini
- ASP Ragusa-Hospital Giovanni Paolo II, 97100 Ragusa, Italy;
| | - Edoardo Masiello
- Radiology Unit, IRCCS San Raffaele Scientific Institute, Via Olgettina 60, 20132 Milan, Italy
| | - Luigi La Via
- Department of Anesthesia and Intensive Care, Azienda Ospedaliero Universitaria Policlinico “G. Rodolico–San Marco”, 95123 Catania, Italy
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19
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Luo H, Yan J, Gong R, Zhang D, Zhou X, Wang X. Identification of biomarkers and pathways for the SARS-CoV-2 infections in obstructive sleep apnea patients based on machine learning and proteomic analysis. BMC Pulm Med 2024; 24:112. [PMID: 38443855 PMCID: PMC10913609 DOI: 10.1186/s12890-024-02921-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2023] [Accepted: 02/22/2024] [Indexed: 03/07/2024] Open
Abstract
BACKGROUND The prevalence of obstructive sleep apnea (OSA) was found to be higher in individuals following COVID-19 infection. However, the intricate mechanisms that underscore this concomitance remain partially elucidated. The aim of this study was to delve deeper into the molecular mechanisms that underpin this comorbidity. METHODS We acquired gene expression profiles for COVID-19 (GSE157103) and OSA (GSE75097) from the Gene Expression Omnibus (GEO) database. Upon identifying shared feature genes between OSA and COVID-19 utilizing LASSO, Random forest and Support vector machines algorithms, we advanced to functional annotation, analysis of protein-protein interaction networks, module construction, and identification of pivotal genes. Furthermore, we established regulatory networks encompassing transcription factor (TF)-gene and TF-miRNA interactions, and searched for promising drug targets. Subsequently, the expression levels of pivotal genes were validated through proteomics data from COVID-19 cases. RESULTS Fourteen feature genes shared between OSA and COVID-19 were selected for further investigation. Through functional annotation, it was indicated that metabolic pathways play a role in the pathogenesis of both disorders. Subsequently, employing the cytoHubba plugin, ten hub genes were recognized, namely TP53, CCND1, MDM2, RB1, HIF1A, EP300, STAT3, CDK2, HSP90AA1, and PPARG. The finding of proteomics unveiled a substantial augmentation in the expression level of HSP90AA1 in COVID-19 patient samples, especially in severe conditions. CONCLUSIONS Our investigation illuminate a mutual pathogenic mechanism that underlies both OSA and COVID-19, which may provide novel perspectives for future investigations into the underlying mechanisms.
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Affiliation(s)
- Hong Luo
- Department of Tuberculosis and Respiratory, Wuhan Jinyintan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Jisong Yan
- Department of Tuberculosis and Respiratory, Wuhan Jinyintan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Rui Gong
- Division of Life Sciences and Medicine, The First Affiliated Hospital of USTC, University of Science and Technology of China (USTC), Hefei, Anhui, China
| | - Dingyu Zhang
- Division of Life Sciences and Medicine, The First Affiliated Hospital of USTC, University of Science and Technology of China (USTC), Hefei, Anhui, China
- Center for Translational Medicine, Wuhan Jinyintan Hospital, Tongji Medical College, Huazhong University of Science and Technology (HUST), Wuhan, Hubei, China
- Department of Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology (HUST), Wuhan, Hubei, China
| | - Xia Zhou
- Department of Tuberculosis and Respiratory, Wuhan Jinyintan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
- Hubei Clinical Research Center for Infectious Diseases, Wuhan, China.
- Wuhan Research Center for Communicable Disease Diagnosis and Treatment, Chinese Academy of Medical Sciences, Wuhan, China.
- Joint Laboratory of Infectious Diseases and Health, Wuhan Institute of Virology and Wuhan Jinyintan Hospital, Chinese Academy of Sciences, Wuhan, China.
| | - Xianguang Wang
- Department of Tuberculosis and Respiratory, Wuhan Jinyintan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
- Hubei Clinical Research Center for Infectious Diseases, Wuhan, China.
- Wuhan Research Center for Communicable Disease Diagnosis and Treatment, Chinese Academy of Medical Sciences, Wuhan, China.
- Joint Laboratory of Infectious Diseases and Health, Wuhan Institute of Virology and Wuhan Jinyintan Hospital, Chinese Academy of Sciences, Wuhan, China.
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20
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Geetha J, Benadict Raja J. An Advanced Circular Adaptive Search Butterfly Optimization Algorithm for the CNN-based Sleep Apnea Detection Approach. IETE JOURNAL OF RESEARCH 2024; 70:1425-1437. [DOI: 10.1080/03772063.2022.2150692] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
Affiliation(s)
- J. Geetha
- Anna University, Chennai, Tamil Nadu, India
| | - J. Benadict Raja
- Department of Computer Science and Engineering, PSNA College of Engineering and Technology, Dindigul, Tamil Nadu, India
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21
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Peixoto de Miranda ÉJF, Mazzotti DR, Santos RB, Souza SP, Parise BK, Giatti S, Aielo AN, Cunha LF, Silva WA, Bortolotto LA, Lorenzi-Filho G, Lotufo PA, Bensenor IM, Bittencourt MS, Drager LF. Incident Coronary Calcium Score in Patients With OSA With and Without Excessive Sleepiness: Brazilian Longitudinal Study of Adult Health. Chest 2024; 165:202-212. [PMID: 37356709 DOI: 10.1016/j.chest.2023.06.025] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2023] [Revised: 05/06/2023] [Accepted: 06/19/2023] [Indexed: 06/27/2023] Open
Abstract
BACKGROUND Uncertainty exists about the impact of OSA and its phenotypes on cardiovascular disease. RESEARCH QUESTION Are OSA and clinical features such as daytime sleepiness associated with incident subclinical coronary atherosclerosis? STUDY DESIGN AND METHODS In this prospective community-based cohort study, we administered a sleepiness questionnaire, actigraphy, and home sleep studies at baseline. Coronary artery calcium (CAC; 64-slice multidetector CT scan imaging) was measured at two different time points throughout the study (baseline, between 2010 and 2014, and follow-up, between 2016 and 2018). Incidence of subclinical atherosclerosis was defined as baseline CAC of 0 followed by CAC of > 0 at a 5-year follow-up visit. The association of incident CAC outcome was assessed using logistic regression. Stratified analyses based on excessive daytime sleepiness (EDS) were performed. RESULTS We analyzed 1,956 participants with available CAC scores at baseline (mean age, 49 ± 8 years; 57.9% female; 32.4% with OSA). In covariate-adjusted analyses (n = 1,247; mean follow-up, 5.1 ± 0.9 years), we found a significant association between OSA and incidence of subclinical atherosclerosis (OR, 1.26; 95% CI, 1.06-1.48), with stronger effects among those reporting EDS (OR, 1.66; 95% CI, 1.30-2.12; P = .028 for interaction). Interestingly, EDS per se was not associated with any CAC outcome. An exploratory analysis of the square root of CAC progression (baseline CAC > 0 followed by a numerical increase in scores at follow-up; n = 319) showed a positive association for both OSA (β = 1.084; 95% CI, 0.032-2.136; P = .043) and OSA with EDS (β = 1.651; 95% CI, 0.208-3.094; P = .025). INTERPRETATION OSA, particularly with EDS, predicts the incidence and progression of CAC. These results support biological plausibility for the increased cardiovascular risk observed among patients with OSA with excessive sleepiness.
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Affiliation(s)
| | - Diego R Mazzotti
- Division of Medical Informatics, Department of Internal Medicine, University of Kansas Medical Center, Kansas City, KS; Division of Pulmonary Critical Care and Sleep Medicine, Department of Internal Medicine, University of Kansas Medical Center, Kansas City, KS
| | - Ronaldo B Santos
- Center for Clinical and Epidemiological Research, University Hospital, São Paulo, SP, Brazil; Unidade de Hipertensão, Instituto do Coração (InCor), São Paulo, SP, Brazil
| | - Silvana P Souza
- Center for Clinical and Epidemiological Research, University Hospital, São Paulo, SP, Brazil; Unidade de Hipertensão, Instituto do Coração (InCor), São Paulo, SP, Brazil
| | - Barbara K Parise
- Center for Clinical and Epidemiological Research, University Hospital, São Paulo, SP, Brazil; Unidade de Hipertensão, Disciplina de Nefrologia, São Paulo, SP, Brazil
| | - Soraya Giatti
- Center for Clinical and Epidemiological Research, University Hospital, São Paulo, SP, Brazil; Unidade de Hipertensão, Disciplina de Nefrologia, São Paulo, SP, Brazil
| | - Aline N Aielo
- Center for Clinical and Epidemiological Research, University Hospital, São Paulo, SP, Brazil; Unidade de Hipertensão, Disciplina de Nefrologia, São Paulo, SP, Brazil
| | - Lorenna F Cunha
- Center for Clinical and Epidemiological Research, University Hospital, São Paulo, SP, Brazil; Unidade de Hipertensão, Disciplina de Nefrologia, São Paulo, SP, Brazil
| | - Wagner A Silva
- Center for Clinical and Epidemiological Research, University Hospital, São Paulo, SP, Brazil; Unidade de Hipertensão, Instituto do Coração (InCor), São Paulo, SP, Brazil
| | - Luiz A Bortolotto
- Unidade de Hipertensão, Instituto do Coração (InCor), São Paulo, SP, Brazil
| | - Geraldo Lorenzi-Filho
- Laboratório do Sono, Disciplina de Pneumologia, Instituto do Coração (InCor), Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brazil
| | - Paulo A Lotufo
- Center for Clinical and Epidemiological Research, University Hospital, São Paulo, SP, Brazil
| | - Isabela M Bensenor
- Center for Clinical and Epidemiological Research, University Hospital, São Paulo, SP, Brazil
| | - Márcio S Bittencourt
- Cardiac CT Program, Heart and Vascular Institute, University of Pittsburgh., Pittsburgh, PA
| | - Luciano F Drager
- Center for Clinical and Epidemiological Research, University Hospital, São Paulo, SP, Brazil; Unidade de Hipertensão, Instituto do Coração (InCor), São Paulo, SP, Brazil; Unidade de Hipertensão, Disciplina de Nefrologia, São Paulo, SP, Brazil.
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22
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Wang C, Chang L, Wang J, Xia L, Cao L, Wang W, Xu J, Gao H. Leptin and risk factors for atherosclerosis: A review. Medicine (Baltimore) 2023; 102:e36076. [PMID: 37986371 PMCID: PMC10659641 DOI: 10.1097/md.0000000000036076] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/20/2023] [Revised: 10/17/2023] [Accepted: 10/20/2023] [Indexed: 11/22/2023] Open
Abstract
Leptin is a hormone secreted primarily by adipose tissue. It regulates an organism's metabolism, energy balance, and body weight through a negative feedback mechanism. When a person or animal has low body fat and little energy, the leptin level in the body decreases, and conversely, when there is an excess of nutrients, the leptin level increases, giving a feeling of satiety. However, when leptin levels are abnormal (too high or too low) for a number of reasons, it can negatively affect your health, inducing inflammatory responses, obesity, and other problems. Many studies have shown that abnormal leptin levels, such as hyperleptinemia, are closely associated with common risk factors for atherosclerosis (AS). This review systematically states the relationship between leptin and common risk factors for AS (inflammation, obesity, diabetes mellitus, hypertension, and sleep disorders) and provides some new thoughts on the future direction of research on both. Because the abnormal level of leptin will have adverse effects on multiple atherosclerotic risk factors, how to regulate the leptin level of patients with AS, and whether we can treat and prevent AS by intervening the leptin level, these may be our new research directions in the future.
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Affiliation(s)
- Cheng Wang
- Affiliated Hospital, Changchun University of Chinese Medicine, Changchun, China
| | - Liping Chang
- Affiliated Hospital, Changchun University of Chinese Medicine, Changchun, China
| | - Jia Wang
- Affiliated Hospital, Changchun University of Chinese Medicine, Changchun, China
| | - Libo Xia
- Affiliated Hospital, Changchun University of Chinese Medicine, Changchun, China
| | - Liyuan Cao
- College of Integrated Traditional Chinese and Western Medicine, Changchun University of Chinese Medicine, Changchun, China
| | - Wei Wang
- School of Traditional Chinese Medicine, Changchun University of Chinese Medicine, Changchun, China
| | - Jianwen Xu
- College of Integrated Traditional Chinese and Western Medicine, Changchun University of Chinese Medicine, Changchun, China
| | - Huize Gao
- School of Traditional Chinese Medicine, Changchun University of Chinese Medicine, Changchun, China
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23
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Wang J, Zhang H, Wu L, Lu D. Sacubitril/valsartan mitigated intermittent hypoxia related intestinal microbiota alteration and aortic injury. Sleep Breath 2023; 27:1769-1777. [PMID: 36719525 DOI: 10.1007/s11325-023-02781-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2022] [Revised: 12/22/2022] [Accepted: 01/23/2023] [Indexed: 02/01/2023]
Abstract
OBJECTIVE To investigate the influence of sacubitril valsartan sodium (SVS) on chronic intermittent hypoxia (IH) related gut microbiome composition alteration and aortic injury. METHODS Experiments were performed using SD rats, which were divided into three groups: control, IH, and SVS group. O2 concentration was decreased to 7-8% at nadir approximately every 3 min in IH group (8 h per day for 6 weeks) or was left unchanged in control group. Rats in SVS group were orally gavaged with SVS at the dosage of 30 mg/kg/day (2 weeks after chronic IH exposure). At week 6, fecal and aortic samples were harvested for 16 s rDNA analysis and histological analysis, respectively. RESULTS Principal coordinate analysis and non-metric multidimensional scaling analysis indicated that the bacterial community was altered by chronic IH exposure, while SVS treatment restored the intestinal microbial communities. Further analysis showed that IH decreased the relative abundance of Lactobacillus and Prevotella, while rats treated with SVS was enriched with Firmicutes, Bacilli, Prevotellaceae, and Lactobacillus, which was similar to control rats. Immunohistochemical staining showed that SVS prevented the upregulation of transforming growth factor-β1 and tumor necrosis factor-alpha in the aorta. CONCLUSION SVS prevented aortic adverse response to IH, possibly through modulating intestinal microbiota.
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Affiliation(s)
- Jinfeng Wang
- Department of Cardiology, The First Affiliated Hospital of Wannan Medical College, Wuhu, 241000, Anhui Province, China
| | - Hongxiang Zhang
- Department of Cardiology, The Second Affiliated Hospital of Wannan Medical College, 10# Kangfu Road, Wuhu, 241000, Anhui Province, China
- Vascular Diseases Research Center of Wannan Medical College, Wuhu, China
| | - LiJuan Wu
- Department of Otolaryngology-Head and Neck Surgery, Yijishan Hospital of Wannan Medical College, Wuhu, China.
| | - Dasheng Lu
- Department of Cardiology, The Second Affiliated Hospital of Wannan Medical College, 10# Kangfu Road, Wuhu, 241000, Anhui Province, China.
- Translational Medicine Center of the Second Hospital Affiliated Wannan Medical College & Pathogens Detection Engineering Center of Wuhu, Wuhu, China.
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24
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Chang JL, Goldberg AN, Alt JA, Alzoubaidi M, Ashbrook L, Auckley D, Ayappa I, Bakhtiar H, Barrera JE, Bartley BL, Billings ME, Boon MS, Bosschieter P, Braverman I, Brodie K, Cabrera-Muffly C, Caesar R, Cahali MB, Cai Y, Cao M, Capasso R, Caples SM, Chahine LM, Chang CP, Chang KW, Chaudhary N, Cheong CSJ, Chowdhuri S, Cistulli PA, Claman D, Collen J, Coughlin KC, Creamer J, Davis EM, Dupuy-McCauley KL, Durr ML, Dutt M, Ali ME, Elkassabany NM, Epstein LJ, Fiala JA, Freedman N, Gill K, Boyd Gillespie M, Golisch L, Gooneratne N, Gottlieb DJ, Green KK, Gulati A, Gurubhagavatula I, Hayward N, Hoff PT, Hoffmann OM, Holfinger SJ, Hsia J, Huntley C, Huoh KC, Huyett P, Inala S, Ishman SL, Jella TK, Jobanputra AM, Johnson AP, Junna MR, Kado JT, Kaffenberger TM, Kapur VK, Kezirian EJ, Khan M, Kirsch DB, Kominsky A, Kryger M, Krystal AD, Kushida CA, Kuzniar TJ, Lam DJ, Lettieri CJ, Lim DC, Lin HC, Liu SY, MacKay SG, Magalang UJ, Malhotra A, Mansukhani MP, Maurer JT, May AM, Mitchell RB, Mokhlesi B, Mullins AE, Nada EM, Naik S, Nokes B, Olson MD, Pack AI, Pang EB, Pang KP, Patil SP, Van de Perck E, Piccirillo JF, Pien GW, et alChang JL, Goldberg AN, Alt JA, Alzoubaidi M, Ashbrook L, Auckley D, Ayappa I, Bakhtiar H, Barrera JE, Bartley BL, Billings ME, Boon MS, Bosschieter P, Braverman I, Brodie K, Cabrera-Muffly C, Caesar R, Cahali MB, Cai Y, Cao M, Capasso R, Caples SM, Chahine LM, Chang CP, Chang KW, Chaudhary N, Cheong CSJ, Chowdhuri S, Cistulli PA, Claman D, Collen J, Coughlin KC, Creamer J, Davis EM, Dupuy-McCauley KL, Durr ML, Dutt M, Ali ME, Elkassabany NM, Epstein LJ, Fiala JA, Freedman N, Gill K, Boyd Gillespie M, Golisch L, Gooneratne N, Gottlieb DJ, Green KK, Gulati A, Gurubhagavatula I, Hayward N, Hoff PT, Hoffmann OM, Holfinger SJ, Hsia J, Huntley C, Huoh KC, Huyett P, Inala S, Ishman SL, Jella TK, Jobanputra AM, Johnson AP, Junna MR, Kado JT, Kaffenberger TM, Kapur VK, Kezirian EJ, Khan M, Kirsch DB, Kominsky A, Kryger M, Krystal AD, Kushida CA, Kuzniar TJ, Lam DJ, Lettieri CJ, Lim DC, Lin HC, Liu SY, MacKay SG, Magalang UJ, Malhotra A, Mansukhani MP, Maurer JT, May AM, Mitchell RB, Mokhlesi B, Mullins AE, Nada EM, Naik S, Nokes B, Olson MD, Pack AI, Pang EB, Pang KP, Patil SP, Van de Perck E, Piccirillo JF, Pien GW, Piper AJ, Plawecki A, Quigg M, Ravesloot MJ, Redline S, Rotenberg BW, Ryden A, Sarmiento KF, Sbeih F, Schell AE, Schmickl CN, Schotland HM, Schwab RJ, Seo J, Shah N, Shelgikar AV, Shochat I, Soose RJ, Steele TO, Stephens E, Stepnowsky C, Strohl KP, Sutherland K, Suurna MV, Thaler E, Thapa S, Vanderveken OM, de Vries N, Weaver EM, Weir ID, Wolfe LF, Tucker Woodson B, Won CH, Xu J, Yalamanchi P, Yaremchuk K, Yeghiazarians Y, Yu JL, Zeidler M, Rosen IM. International Consensus Statement on Obstructive Sleep Apnea. Int Forum Allergy Rhinol 2023; 13:1061-1482. [PMID: 36068685 PMCID: PMC10359192 DOI: 10.1002/alr.23079] [Show More Authors] [Citation(s) in RCA: 128] [Impact Index Per Article: 64.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2022] [Revised: 08/12/2022] [Accepted: 08/18/2022] [Indexed: 11/08/2022]
Abstract
BACKGROUND Evaluation and interpretation of the literature on obstructive sleep apnea (OSA) allows for consolidation and determination of the key factors important for clinical management of the adult OSA patient. Toward this goal, an international collaborative of multidisciplinary experts in sleep apnea evaluation and treatment have produced the International Consensus statement on Obstructive Sleep Apnea (ICS:OSA). METHODS Using previously defined methodology, focal topics in OSA were assigned as literature review (LR), evidence-based review (EBR), or evidence-based review with recommendations (EBR-R) formats. Each topic incorporated the available and relevant evidence which was summarized and graded on study quality. Each topic and section underwent iterative review and the ICS:OSA was created and reviewed by all authors for consensus. RESULTS The ICS:OSA addresses OSA syndrome definitions, pathophysiology, epidemiology, risk factors for disease, screening methods, diagnostic testing types, multiple treatment modalities, and effects of OSA treatment on multiple OSA-associated comorbidities. Specific focus on outcomes with positive airway pressure (PAP) and surgical treatments were evaluated. CONCLUSION This review of the literature consolidates the available knowledge and identifies the limitations of the current evidence on OSA. This effort aims to create a resource for OSA evidence-based practice and identify future research needs. Knowledge gaps and research opportunities include improving the metrics of OSA disease, determining the optimal OSA screening paradigms, developing strategies for PAP adherence and longitudinal care, enhancing selection of PAP alternatives and surgery, understanding health risk outcomes, and translating evidence into individualized approaches to therapy.
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Affiliation(s)
- Jolie L. Chang
- University of California, San Francisco, California, USA
| | | | | | | | - Liza Ashbrook
- University of California, San Francisco, California, USA
| | | | - Indu Ayappa
- Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | | | | | | | | | - Maurits S. Boon
- Sidney Kimmel Medical Center at Thomas Jefferson University, Philadelphia, Pennsylvania, USA
| | - Pien Bosschieter
- Academic Centre for Dentistry Amsterdam, Amsterdam, The Netherlands
| | - Itzhak Braverman
- Hillel Yaffe Medical Center, Hadera Technion, Faculty of Medicine, Hadera, Israel
| | - Kara Brodie
- University of California, San Francisco, California, USA
| | | | - Ray Caesar
- Stone Oak Orthodontics, San Antonio, Texas, USA
| | | | - Yi Cai
- University of California, San Francisco, California, USA
| | | | | | | | | | | | | | | | | | - Susmita Chowdhuri
- Wayne State University and John D. Dingell VA Medical Center, Detroit, Michigan, USA
| | - Peter A. Cistulli
- Faculty of Medicine and Health, University of Sydney, Sydney, Australia
| | - David Claman
- University of California, San Francisco, California, USA
| | - Jacob Collen
- Uniformed Services University, Bethesda, Maryland, USA
| | | | | | - Eric M. Davis
- University of Virginia, Charlottesville, Virginia, USA
| | | | | | - Mohan Dutt
- University of Michigan, Ann Arbor, Michigan, USA
| | - Mazen El Ali
- University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | | | | | | | | | - Kirat Gill
- Stanford University, Palo Alto, California, USA
| | | | - Lea Golisch
- University Hospital Mannheim, Ruprecht-Karls-University Heidelberg, Heidelberg, Germany
| | | | | | | | - Arushi Gulati
- University of California, San Francisco, California, USA
| | | | | | - Paul T. Hoff
- University of Michigan, Ann Arbor, Michigan, USA
| | - Oliver M.G. Hoffmann
- University Hospital Mannheim, Ruprecht-Karls-University Heidelberg, Heidelberg, Germany
| | | | - Jennifer Hsia
- University of Minnesota, Minneapolis, Minnesota, USA
| | - Colin Huntley
- Sidney Kimmel Medical Center at Thomas Jefferson University, Philadelphia, Pennsylvania, USA
| | | | | | - Sanjana Inala
- Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | | | | | | | | | | | | | | | | | | | - Meena Khan
- Ohio State University, Columbus, Ohio, USA
| | | | - Alan Kominsky
- Cleveland Clinic Head and Neck Institute, Cleveland, Ohio, USA
| | - Meir Kryger
- Yale School of Medicine, New Haven, Connecticut, USA
| | | | | | | | - Derek J. Lam
- Oregon Health and Science University, Portland, Oregon, USA
| | | | | | | | | | | | | | - Atul Malhotra
- University of California, San Diego, California, USA
| | | | - Joachim T. Maurer
- University Hospital Mannheim, Ruprecht-Karls-University Heidelberg, Heidelberg, Germany
| | - Anna M. May
- Case Western Reserve University, Cleveland, Ohio, USA
| | - Ron B. Mitchell
- University of Texas, Southwestern and Children’s Medical Center Dallas, Texas, USA
| | | | | | | | | | - Brandon Nokes
- University of California, San Diego, California, USA
| | | | - Allan I. Pack
- University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | | | | | | | | | | | | | | | | | - Mark Quigg
- University of Virginia, Charlottesville, Virginia, USA
| | | | - Susan Redline
- Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | | | - Armand Ryden
- Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, California, USA
| | | | - Firas Sbeih
- Cleveland Clinic Head and Neck Institute, Cleveland, Ohio, USA
| | | | | | | | | | - Jiyeon Seo
- University of California, Los Angeles, California, USA
| | - Neomi Shah
- Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | | | | | - Ryan J. Soose
- University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | | | - Erika Stephens
- University of California, San Francisco, California, USA
| | | | | | | | | | - Erica Thaler
- University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Sritika Thapa
- Yale School of Medicine, New Haven, Connecticut, USA
| | | | - Nico de Vries
- Academic Centre for Dentistry Amsterdam, Amsterdam, The Netherlands
| | | | - Ian D. Weir
- Yale School of Medicine, New Haven, Connecticut, USA
| | | | | | | | - Josie Xu
- University of Toronto, Ontario, Canada
| | | | | | | | | | | | - Ilene M. Rosen
- University of Pennsylvania, Philadelphia, Pennsylvania, USA
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25
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Kundel V, Cohen O, Khan S, Patel M, Kim-Schulze S, Kovacic J, Suárez-Fariñas M, Shah NA. Advanced Proteomics and Cluster Analysis for Identifying Novel Obstructive Sleep Apnea Subtypes before and after Continuous Positive Airway Pressure Therapy. Ann Am Thorac Soc 2023; 20:1038-1047. [PMID: 36780659 PMCID: PMC12039956 DOI: 10.1513/annalsats.202210-897oc] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2022] [Accepted: 02/13/2023] [Indexed: 02/15/2023] Open
Abstract
Rationale: Studies have shown elevated inflammatory biomarkers in obstructive sleep apnea (OSA), but data after continuous positive airway pressure (CPAP) treatment are inconsistent. Objectives: We used the Olink proteomics panel to identify unique OSA clusters on the basis of inflammatory protein expression and assess the impact of CPAP therapy. Methods: Adults with newly diagnosed OSA had blood drawn at baseline and three to four months after CPAP. Samples were analyzed using the Olink proteomics platform, which measures 92 prespecified inflammatory proteins using proximity extension assay. Linear mixed-effects models were used to model changes in protein expression during the period of CPAP use, adjusting for batch, age, and sex. Unsupervised hierarchical clustering was performed to identify unique inflammatory OSA clusters on the basis of inflammatory biomarkers. Within-cluster impact of CPAP on inflammatory protein expression was assessed. Results: Among 46 patients, the mean age was 46 ± 12 years (22% women), mean body mass index was 31 ± 5 kg/m2, and mean respiratory disturbance index was 33 ± 17 events/hour. Unsupervised cluster and heatmap analysis revealed three unique proteomic clusters, with low (n = 21), intermediate (n = 19), and high (n = 6) inflammatory protein expression. After CPAP, there were significant within-cluster differences in protein expression. The low inflammatory cluster had a significant increase in protein expression (16%; P = 0.02), and the high inflammatory cluster had a significant decrease in protein expression (-20%; P = 0.003), more significant among those compliant with CPAP in the low (25%; P = 0.04) and high (-22%; P = 0.01) clusters. Conclusions: We identified three unique inflammatory clusters in patients with OSA using plasma proteomics, with a differential response to CPAP by cluster. Our results are hypothesis generating and require further investigation in larger longitudinal studies for enhanced cardiovascular risk profiling in OSA.
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Affiliation(s)
| | - Oren Cohen
- Division of Pulmonary, Critical Care and Sleep Medicine
| | - Samira Khan
- Division of Pulmonary, Critical Care and Sleep Medicine
| | - Manishkumar Patel
- Human Immune Monitoring Center, Hess Center for Science and Medicine
| | | | - Jason Kovacic
- Cardiovascular Research Institute, and
- Victor Chang Cardiac Research Institute, Darlinghurst, New South Wales, Australia; and
- St. Vincent's Clinical School, University of New South Wales, Sydney, New South Wales, Australia
| | - Mayte Suárez-Fariñas
- Center for Biostatistics, Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Neomi A Shah
- Division of Pulmonary, Critical Care and Sleep Medicine
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Altay S, Fırat S, Peker Y. A Narrative Review of the Association of Obstructive Sleep Apnea with Hypertension: How to Treat Both When They Coexist? J Clin Med 2023; 12:4144. [PMID: 37373837 DOI: 10.3390/jcm12124144] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2023] [Revised: 06/07/2023] [Accepted: 06/13/2023] [Indexed: 06/29/2023] Open
Abstract
Hypertension (HT) is a worldwide public health issue and an essential risk factor for cardiovascular and cerebrovascular diseases. Obstructive sleep apnea (OSA) is a condition characterized by recurrent episodes of apnea and hypopnea as a consequence of partial or complete obstruction of the upper airways due to anatomic and/or functional disturbances. There is mounting evidence of a relationship between OSA and HT. In patients with OSA, HT is predominantly nocturnal and characterized by high diastolic blood pressure and usually by a nondipping pattern. Optimizing the blood pressure control is recommended in the current guidelines as the first treatment option in hypertensive patients with OSA. Continuous positive airway pressure (CPAP) therapy may reduce blood pressure, albeit only slightly as a stand-alone treatment. CPAP, as an add-on treatment to antihypertensive medication, appears to be an efficient treatment modality when both conditions coexist. This narrative review aims to summarize the current perspectives on the association of OSA with HT and the treatment options available for adults with OSA-related HT.
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Affiliation(s)
- Servet Altay
- Department of Cardiology, Trakya University School of Medicine, Edirne 22030, Turkey
| | - Selma Fırat
- Department of Pulmonary Medicine, University of Health Sciences, Atatürk Sanatorium Education and Research Hospital, Ankara 06280, Turkey
| | - Yüksel Peker
- Department of Pulmonary Medicine, Koç University School of Medicine, Istanbul 34450, Turkey
- Division of Sleep and Circadian Disorders, Brigham and Women's Hospital, Boston, MA 02115, USA
- Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA
- Department of Clinical Sciences, Respiratory Medicine and Allergology, Faculty of Medicine, Lund University, 22002 Lund, Sweden
- Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, 40530 Gothenburg, Sweden
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Luo S, Ma X, Wu W, Lin S, Li M, Zhang Z, Zhu P, Song Z. Continuous Hypobaric Hypoxia may Promote Atherosclerosis Progression in Apolipoprotein E-deficient Mice. Int J Med Sci 2023; 20:849-857. [PMID: 37324194 PMCID: PMC10266041 DOI: 10.7150/ijms.78362] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/25/2022] [Accepted: 04/07/2023] [Indexed: 06/17/2023] Open
Abstract
Background: Intermittent normobaric hypoxia can promote the progression of atherosclerotic plaques. However, the effect of continuous hypobaric hypoxia (CHH), which is a major feature of high-altitude environment, on atherosclerosis has not been investigated thoroughly. Materials and Methods: After eight weeks of high-cholesterol diet, 30 male ApoE-/- mice were randomly divided into control and CHH groups. Mice in the CHH group lived in a hypobaric chamber with an oxygen content of 10% and air pressure of 364 mmhg (equal to 5,800 m altitude above sea level) for 4 weeks, while mice in the control group lived in normoxia condition. Then all mice were euthanized and the atherosclerotic lesion size and plaque stability in the aortic root were assessed. Intraplaque angiogenesis was characterized by immunostaining of CD31 and endomucin, which are identified as specific markers of vascular endothelial cells. Immunohistochemistry and qRT-PCR were performed to measure inflammatory cytokines. Results: Four weeks of CHH exposure promoted the growth of atherosclerotic lesions (p=0.0017) and decreased the stability of atherosclerotic plaques. In CHH group, plaque smooth muscle cells and collagen contents decreased, while plaque macrophages and lipids contents increased significantly (p<0.001). The contents of CD31 (p=0.0379) and endomucin (p=0.0196) in the plaque was higher in the CHH group and correlated with angiogenesis progression. Further, the content of monocyte chemotactic protein-1 (p=0.0376) and matrix metalloproteinase-2 was significantly higher (p=0.0212) in the CHH group. Conclusions: CHH may accelerate atherosclerosis progression in ApoE-/- mice by promoting angiogenesis and inflammation.
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Affiliation(s)
- Shouming Luo
- Department of Cardiovascular Medicine, Center for Circadian Metabolism and Cardiovascular Disease, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China
| | - Xiaogen Ma
- Department of Cardiovascular Medicine, Center for Circadian Metabolism and Cardiovascular Disease, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China
| | - Weiqiang Wu
- Department of Cardiovascular Medicine, Center for Circadian Metabolism and Cardiovascular Disease, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China
| | - Shu Lin
- Department of Cardiovascular Medicine, Center for Circadian Metabolism and Cardiovascular Disease, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China
- Group of Neuroendocrinology, Diabetes and Metabolism Division, Garvan Institute of Medical Research, Sydney, New South Wales, Australia
- The Second Affiliated Hospital, Fujian Medical University, Quanzhou, China
| | - Mindian Li
- Department of Cardiovascular Medicine, Center for Circadian Metabolism and Cardiovascular Disease, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China
| | - Zhihui Zhang
- Department of Cardiovascular Medicine, Center for Circadian Metabolism and Cardiovascular Disease, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China
| | - Ping Zhu
- Department of Cardiovascular Medicine, Center for Circadian Metabolism and Cardiovascular Disease, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China
| | - Zhiyuan Song
- Department of Cardiovascular Medicine, Center for Circadian Metabolism and Cardiovascular Disease, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China
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Agca FV, Sensoy B, Aslanci ME, Ulutas HG, Gunes A. Retinal microvascular changes in patients with coronary artery disease and apnea. Microvasc Res 2023; 148:104514. [PMID: 36894026 DOI: 10.1016/j.mvr.2023.104514] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2022] [Revised: 02/06/2023] [Accepted: 03/01/2023] [Indexed: 03/09/2023]
Abstract
BACKGROUND Optical coherence tomography angiography (OCT-A) allowed visualization of capillary level of retina; however, the relationship between coronary vascular status and retinal microvascular changes in patients with apnea is not known well. Our aim was to assess the retinal OCT-A parameters in patients with ischemia and angiographically proven microvascular disease and compare them with obstructive coronary disease in patients with apnea. METHODS Our observational study included 185 eyes of 185 patients, 123 eyes of patients with apnea (72 eyes from mild OSAS, 51 eyes from moderate to severe OSAS) and 62 eyes from healthy controls. Radial scans of the macula and OCT-A scans of the central macula (superficial (SCP) and deep (DCP) capillary plexuses) were performed on all participants. All participants had documented sleep apnea disorder within 2 years prior to coronary angiography. Patients were grouped by severity of apnea and coronary atherosclerosis (50 % stenosis cut-off value for obstructive coronary artery disease). Patients presented with myocardial ischemia and without coronary artery occlusion (<50 % diameter reduction or FFR > 0.80) constitute the microvascular coronary artery (INOCA) group. RESULTS Compared to healthy controls, patients with apnea showed deterioration in vascular density in all regions of the retina, regardless of obstructive or microvascular coronary artery disease on the ischemia background. This study has provided important observations of a high prevalence of INOCA in patients with OSAS and the presence of OSAS was a significant independent predictor of functional coronary artery disease. The relative decreases in vascular densities were more pronounced in the DCP layer according to SCP layer of macula. Only FAZ area values were significantly different according to the severity of OSAS (0.27 (0.11-0.62) and 0.23 (0.07-0.50) (p = 0.012)). CONCLUSIONS In patients with apnea, OCT-A can be used as a noninvasive tool to define coronary artery involvement, with similar retinal microvascular changes both in obstructive and microvascular coronary artery group. In patients with OSAS, we observed a high prevalence of microvascular coronary disease, supporting pathophysiological role of OSAS in ischemia of this group of patients.
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Affiliation(s)
- Fahriye Vatansever Agca
- Saglik Bilimleri University, Bursa Yuksek Ihtisas Training and Research Hospital, Cardiology Clinic Bursa, Turkey.
| | - Baris Sensoy
- Saglik Bilimleri University, Bursa Yuksek Ihtisas Training and Research Hospital, Cardiology Clinic Bursa, Turkey
| | - Mehmet Emin Aslanci
- Saglik Bilimleri University, Bursa Yuksek Ihtisas Training and Research Hospital, Ophthalmology Clinic Bursa, Turkey
| | - Hafize Gokben Ulutas
- Saglik Bilimleri University, Bursa Yuksek Ihtisas Training and Research Hospital, Ophthalmology Clinic Bursa, Turkey
| | - Aygul Gunes
- Saglik Bilimleri University, Bursa Yuksek Ihtisas Training and Research Hospital, Neurology Clinic Bursa, Turkey
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Ou YH, Tan A, Lee CH. Management of hypertension in obstructive sleep apnea. Am J Prev Cardiol 2023; 13:100475. [PMID: 36873802 PMCID: PMC9976208 DOI: 10.1016/j.ajpc.2023.100475] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2022] [Revised: 02/08/2023] [Accepted: 02/12/2023] [Indexed: 02/17/2023] Open
Abstract
Obstructive sleep apnea (OSA) plays an important role in the development of hypertension. Thus, this review summarizes pharmacological and non-pharmacological approaches to blood pressure (BP) control in patients with OSA. Current treatments for OSA, such as continuous positive airway pressure, are effective at lowering BP. However, they only provide a modest BP reduction, and pharmacological treatment remains important for achieving optimal BP control. Furthermore, current guidelines for the treatment of hypertension do not make specific recommendations on pharmacological treatment protocols for controlling BP in patients with OSA. Moreover, the BP-lowering effects of various classes of antihypertensives may be different in hypertensive patients with OSA than in those without OSA due to the underlying mechanisms that promote hypertension in OSA. The acute and chronic increase in sympathetic nerve activity in patients with OSA explain the effectiveness of beta blockers in controlling BP in these patients. As activation of the renin-angiotensin-aldosterone system may also promote hypertension in OSA, angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers have generally been found effective for lowering BP in hypertensive patients with OSA. The aldosterone antagonist spironolactone also produces a good antihypertensive response in patients with OSA and resistant hypertension. However, there are limited data available that compare the effects of various classes of antihypertensive medication on BP control in those with OSA, and most data have been obtained from small-scale studies. This demonstrates the need for large-scale randomized controlled trials to evaluate a range of BP-lowering regimens in patients with OSA and hypertension.
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Affiliation(s)
- Yi-Hui Ou
- Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Adeline Tan
- Department of Respiratory Medicine, Ng Teng Fong General Hospital, Singapore
| | - Chi-Hang Lee
- Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
- Department of Cardiology, National University Heart Centre Singapore, Singapore
- Cardiovascular Research Institute, National University of Singapore, Singapore
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AlSheikh S. Relationship Between Peripheral Arterial Diseases and Obstructive Sleep Apnea: A Systematic Review. Cureus 2023; 15:e35550. [PMID: 37007316 PMCID: PMC10058385 DOI: 10.7759/cureus.35550] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/27/2023] [Indexed: 03/03/2023] Open
Abstract
Although the effects of obstructive sleep apnea (OSA) on the cardiovascular outcomes of coronary artery disease (CAD) have been well-established, its significance on the occurrence of peripheral arterial disease (PAD) remains debatable. Prompt diagnosis and treatment of OSA would help reduce cardiovascular comorbidities. Our study aimed to assess the relationship between OSA and PAD and report any statistical association between the two conditions. Here, we investigated the prevalence and association of OSA in PAD based on related articles from PubMed, Embase, and the Cochrane Library. All databases were systematically searched from January 2000 to December 2020. A total of 238 articles deemed relevant were assessed for eligibility, of which seven articles were selected for the systematic review. Seven prospective cohorts were qualified for inclusion, which included 26,881 male and 34,403 female patients (N = 61,284). The retrieved articles described OSA severity based on the apnea-hypopnea index and reported increased OSA prevalence in PAD patients. The Epworth sleepiness scale showed no association between OSA severity, poor ankle-brachial index values, and increased daytime sleepiness. The prevalence of OSA increased in patients with PAD. Further research and prospective clinical trials are required to establish strong associations between OSA and PAD to make appropriate changes in patient management algorithms and improve their outcomes.
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Prognostic Implications of OSA in Acute Coronary Syndrome by Obesity Status. Chest 2023:S0012-3692(23)00173-3. [PMID: 36764513 DOI: 10.1016/j.chest.2023.02.001] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2022] [Revised: 12/20/2022] [Accepted: 02/01/2023] [Indexed: 02/11/2023] Open
Abstract
BACKGROUND A close relationship exists between OSA and obesity. The impact of obesity on the prognostic significance of OSA in patients with acute coronary syndrome (ACS) remains unclear. RESEARCH QUESTION Do the effects of OSA on subsequent cardiovascular events in patients with ACS vary with obesity status? STUDY DESIGN AND METHODS This is a prospective cohort study. Patients 18 to 85 years of age and hospitalized for ACS were consecutively enrolled and underwent portable sleep monitoring after clinical stabilization. OSA was defined as an apnea hypopnea index ≥ 15 events/h. The primary end point was major adverse cardiovascular and cerebrovascular event (MACCE), including cardiovascular death, hospitalization for ACS, stroke, ischemia-driven revascularization, or hospitalization for heart failure. RESULTS Among 1,920 patients enrolled (84.5% men; mean age ± SD, 56.4 ± 10.5 years), 1,013 (52.8%) had OSA, and 718 (37.4%) were obese (BMI ≥ 28 kg/m2). During 2.9 years (1.5, 3.6) follow up, the incidence of MACCE was significantly higher in patients with obesity than in patients without obesity (hazard ratio [HR], 1.29; 95% CI, 1.06-1.58; P = .013). Although the prevalence of OSA was lower in patients without obesity than in those with obesity (43.9% vs 67.5%, P < .001), OSA independently predicted the incidence of MACCE only in patients without obesity (adjusted HR, 1.34; 95% CI, 1.03-1.75; P = .03), but not in patients with obesity (adjusted HR, 1.10; 95% CI, 0.78-1.55; P = .58). No significant interaction between obesity and OSA was noted (P for interaction = .35). The incremental risk associated with OSA in patients without obesity might be explained by more hospitalization for ACS and ischemia-driven revascularization. INTERPRETATION For patients with ACS, OSA was independently associated with an increased risk of subsequent events, particularly among patients without obesity. These findings highlight the importance of identifying OSA in nonobese patients with ACS. CLINICAL TRIAL REGISTRATION ClinicalTrials.gov; No.: NCT03362385; URL: www. CLINICALTRIALS gov.
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Proteomic profiling for prediction of recurrent cardiovascular event in patients with acute coronary syndrome and obstructive sleep apnea: A post-hoc analysis from the ISAACC study. Biomed Pharmacother 2023; 158:114125. [PMID: 36549084 DOI: 10.1016/j.biopha.2022.114125] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2022] [Revised: 11/28/2022] [Accepted: 12/09/2022] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND Obstructive sleep apnea (OSA) is associated with a recurrent cardiovascular event (CVE) risk in patients with a first acute coronary syndrome (ACS). However, the pathological pathways by which OSA promotes this deleterious role are unknown. We aim to explore the proteomic profile associated with OSA that promote the recurrent CVE risk in severe OSA patients with ACS without previous cardiovascular diseases. METHODS This post-hoc analysis from the ISAACC study (NCT01335087) included 86 patients admitted for ACS. Patients underwent respiratory polygraphy for the first 24-72 h to OSA diagnosis. We analyzed of 276 cardiovascular and inflammatory related proteins in baseline fasting plasma samples using proximity expression assay technology (Olink®, Sweden). Protein levels were compared between severe OSA patients with/without recurrent CVEs during follow-up. Random forest was conducted to select relevant proteins and generate a predictive model of recurrent CVE. RESULTS We included 86 patients (median age: 61 years, median BMI: 29.4 kg/m2 and 86 % males) admitted for ACS with severe OSA (56 without recurrent CVE/30 with recurrent CVE). The plasma levels of 38 proteins were differentially expressed between groups. Additionally, 12 proteins had a significant association with respiratory polygraphy parameters. Three proteins discriminate with an AUC of 0.81 (95 % CI of 0.71-0.9) between severe OSA patients with and without recurrent CVE. These proteins were implicated in cell proliferation, communication and apoptosis, and regulation/response to the inflammatory and immune systems. CONCLUSION In ACS patients with severe OSA, a proteomic profile was associated with recurrent CVEs. This proteomic profile was correlated with specific OSA parameters from respiratory polygraphy. Proteomic profiling may provide an new direction for patient risk stratification and clinical management.
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Ji P, Kou Q, Zhang J. Study on Relationship Between Carotid Intima-Media Thickness and Inflammatory Factors in Obstructive Sleep Apnea. Nat Sci Sleep 2022; 14:2179-2187. [PMID: 36540195 PMCID: PMC9760046 DOI: 10.2147/nss.s389253] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/08/2022] [Accepted: 11/27/2022] [Indexed: 12/15/2022] Open
Abstract
Purpose The purpose of this study was to explore the change of carotid intima-media thickness (IMT) and its correlation with inflammatory markers in patients with different degrees of obstructive sleep apnea (OSA). Methods One hundred hospitalized patients were selected and were divided into the normal control group (21 cases), the mild-moderate group (39 cases) and the severe group (40 cases) according to their apnea hypopnea index (AHI). Carotid IMT of all registered patients was studied with ultrasound, and serum levels of high-sensitivity C-reactive protein (hs-CRP), Lipoprotein-associated phospholipaseA2 (Lp-PLA2) and tumor necrosis factor-α (TNF-α) were measured. Pearson correlation analysis and multiple stepwise regression analysis were used to analyze the correlation between carotid IMT and inflammatory factors. Results Patients with mild, moderate and severe OSA Carotid IMT had significantly higher levels of serum hs-CRP, Lp-PLA2 and TNF-α compared with the normal control group (P < 0.001). The levels of carotid IMT, serum protein hs-CRP, Lp-PLA2 and TNF-α in the severe OSA group were significantly higher than those of the mild-moderate OSA group, with P values being less than 0.001. Carotid artery IMT was positively correlated with serum hs-CRP (r = 0.83, P < 0.001), Lp-PLA2 (r =0.58, P < 0.001), and TNF-α (r =0.69, P < 0.001). hs-CRP, TNF-α and AHI were independent factors affecting carotid artery IMT. In addition, AHI was an independent indicator of carotid atherosclerosis (P = 0.0012). Conclusion Increased inflammatory factors in OSA patients might cause the progression of atherosclerosis, which might increase the risk of cardiovascular and cerebrovascular diseases in OSA patients.
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Affiliation(s)
- Peng Ji
- Zhengzhou University People’s Hospital, Zhengzhou, People’s Republic of China
- Department of Neurology, The Third People’s Hospital of Zhengzhou (Tumor Hospital Affiliated of Henan University), Zhengzhou, People’s Republic of China
| | - Qixing Kou
- Department of Neurology, The Third People’s Hospital of Zhengzhou (Tumor Hospital Affiliated of Henan University), Zhengzhou, People’s Republic of China
| | - Jiewen Zhang
- Department of Neurology, Zhengzhou University People’s Hospital, Zhengzhou, People’s Republic of China
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Guo S, Zhou Y, Xie X. Resveratrol inhibiting TGF/ERK signaling pathway can improve atherosclerosis: backgrounds, mechanisms and effects. Biomed Pharmacother 2022; 155:113775. [DOI: 10.1016/j.biopha.2022.113775] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2022] [Revised: 09/16/2022] [Accepted: 09/28/2022] [Indexed: 11/02/2022] Open
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Du Z, Sun H, Du Y, Li L, Lv Q, Yu H, Li F, Wang Y, Jiao X, Hu C, Qin Y. Comprehensive Metabolomics and Machine Learning Identify Profound Oxidative Stress and Inflammation Signatures in Hypertensive Patients with Obstructive Sleep Apnea. Antioxidants (Basel) 2022; 11:antiox11101946. [PMID: 36290670 PMCID: PMC9598902 DOI: 10.3390/antiox11101946] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2022] [Revised: 09/19/2022] [Accepted: 09/23/2022] [Indexed: 11/16/2022] Open
Abstract
Obstructive sleep apnea (OSA) can aggravate blood pressure and increase the risk of cardiovascular diseases in hypertensive individuals, yet the underlying pathophysiological process is still incompletely understood. More importantly, OSA remains a significantly undiagnosed condition. In this study, a total of 559 hypertensive patients with and without OSA were included. Metabolome and lipidome-wide analyses were performed to explore the pathophysiological processes of hypertension comorbid OSA and derive potential biomarkers for diagnosing OSA in hypertensive subjects. Compared to non-OSA hypertensive patients (discovery set = 120; validation set = 116), patients with OSA (discovery set = 165; validation set = 158) demonstrated a unique sera metabolic phenotype dominated by abnormalities in biological processes of oxidative stress and inflammation. By integrating three machine learning algorithms, six discriminatory metabolites (including 5-hydroxyeicosatetraenoic acid, taurine, histidine, lysophosphatidic acid 16:0, lysophosphatidylcholine 18:0, and dihydrosphingosine) were selected for constructing diagnostic and classified model. Notably, the established multivariate-model could accurately identify OSA subjects. The corresponding area under the curve values and the correct classification rates were 0.995 and 96.8% for discovery sets, 0.997 and 99.1% for validation sets. This work updates the molecular insights of hypertension comorbid OSA and paves the way for the use of metabolomics for the diagnosis of OSA in hypertensive individuals.
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Affiliation(s)
- Zhiyong Du
- The Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education, National Clinical Research Center for Cardiovascular Diseases, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, China
- Beijing Institute of Heart Lung and Blood Vessel Disease, Beijing 100029, China
| | - Haili Sun
- The Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education, National Clinical Research Center for Cardiovascular Diseases, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, China
- Beijing Institute of Heart Lung and Blood Vessel Disease, Beijing 100029, China
| | - Yunhui Du
- The Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education, National Clinical Research Center for Cardiovascular Diseases, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, China
- Beijing Institute of Heart Lung and Blood Vessel Disease, Beijing 100029, China
| | - Linyi Li
- The Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education, National Clinical Research Center for Cardiovascular Diseases, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, China
- Beijing Institute of Heart Lung and Blood Vessel Disease, Beijing 100029, China
| | - Qianwen Lv
- The Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education, National Clinical Research Center for Cardiovascular Diseases, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, China
- Beijing Institute of Heart Lung and Blood Vessel Disease, Beijing 100029, China
| | - Huahui Yu
- The Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education, National Clinical Research Center for Cardiovascular Diseases, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, China
- Beijing Institute of Heart Lung and Blood Vessel Disease, Beijing 100029, China
| | - Fan Li
- The Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education, National Clinical Research Center for Cardiovascular Diseases, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, China
- Beijing Institute of Heart Lung and Blood Vessel Disease, Beijing 100029, China
| | - Yu Wang
- The Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education, National Clinical Research Center for Cardiovascular Diseases, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, China
- Beijing Institute of Heart Lung and Blood Vessel Disease, Beijing 100029, China
| | - Xiaolu Jiao
- The Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education, National Clinical Research Center for Cardiovascular Diseases, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, China
- Beijing Institute of Heart Lung and Blood Vessel Disease, Beijing 100029, China
| | - Chaowei Hu
- The Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education, National Clinical Research Center for Cardiovascular Diseases, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, China
- Beijing Institute of Heart Lung and Blood Vessel Disease, Beijing 100029, China
| | - Yanwen Qin
- The Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education, National Clinical Research Center for Cardiovascular Diseases, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, China
- Beijing Institute of Heart Lung and Blood Vessel Disease, Beijing 100029, China
- Correspondence: ; Tel./Fax: +86-10-64456529
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Hasan R, Genta PR, Pinheiro GDL, Garcia ML, Scudeller PG, de Carvalho CRR, Lorenzi-Filho G. Validation of an overnight wireless high-resolution oximeter for the diagnosis of obstructive sleep apnea at home. Sci Rep 2022; 12:15136. [PMID: 36071120 PMCID: PMC9452585 DOI: 10.1038/s41598-022-17698-8] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2022] [Accepted: 07/29/2022] [Indexed: 12/02/2022] Open
Abstract
Obstructive sleep apnea (OSA) is extremely common and has several consequences. However, most cases remain undiagnosed. One limitation is the lack of simple and validated methods for OSA diagnosis at home. The aim of this study was to validate a wireless high-resolution oximeter with a built-in accelerometer linked to a smartphone with automated cloud analysis (Biologix) that was compared with a home sleep test (HST, Apnea Link Air) performed on the same night. We recruited 670 patients out of a task force of 1013 patients with suspected OSA who were referred to our center for diagnosis. The final sample consisted of 478 patients (mean age: 56.7 ± 13.1 years, mean body mass index: 31.9 ± 6.3 kg/m2). To estimate the night-to-night OSA severity variability, 62 patients underwent HST for two consecutive nights. The HST-apnea–hypopnea index (AHI) and the Biologix-oxygen desaturation index (ODI) was 25.0 ± 25.0 events/h and 24.9 ± 26.5 events/h, respectively. The area under the curve—sensibility/specificity to detect at least mild (HST-AHI > 5), moderate-to-severe (HST-AHI > 15), and severe OSA (HST-AHI > 30) were (0.983)—94.7/92.8, (0.986)—94.8/93.9, and (0.990)—95.8/94.3, respectively. The limits of agreement originating from the Bland–Altman plot and the correlation between HST-AHI and Biologix-ODI were lower than the night-to-night HST-AHI variability (25.5 and 34.5 events/h, respectively, p = 0.001). We conclude that Biologix is a simple and reliable technique for OSA diagnosis at home.
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Affiliation(s)
- Rosa Hasan
- Laboratorio do Sono, LIM 63, Instituto de Psiquiatria (IPq), Hospital das Clínicas HCFMUSP, Universidade de Sao Paulo, Sao Paulo, SP, Brazil.,Laboratorio do Sono, LIM 63, Divisão de Pneumologia, Instituto do Coraçao, InCor, Hospital das Clínicas HCFMUSP, Universidade de Sao Paulo, Eneas de Carvalho Aguiar 44, 8º andar, Sao Paulo, SP, 05403-900, Brazil
| | - Pedro Rodrigues Genta
- Laboratorio do Sono, LIM 63, Divisão de Pneumologia, Instituto do Coraçao, InCor, Hospital das Clínicas HCFMUSP, Universidade de Sao Paulo, Eneas de Carvalho Aguiar 44, 8º andar, Sao Paulo, SP, 05403-900, Brazil
| | - George do Lago Pinheiro
- Laboratorio do Sono, LIM 63, Divisão de Pneumologia, Instituto do Coraçao, InCor, Hospital das Clínicas HCFMUSP, Universidade de Sao Paulo, Eneas de Carvalho Aguiar 44, 8º andar, Sao Paulo, SP, 05403-900, Brazil
| | - Michelle Louvaes Garcia
- Laboratorio do Sono, LIM 63, Divisão de Pneumologia, Instituto do Coraçao, InCor, Hospital das Clínicas HCFMUSP, Universidade de Sao Paulo, Eneas de Carvalho Aguiar 44, 8º andar, Sao Paulo, SP, 05403-900, Brazil
| | - Paula Gobi Scudeller
- Divisão de Pneumologia, Instituto do Coraçao, InCor, Hospital das Clínicas HCFMUSP, Universidade de Sao Paulo, Sao Paulo, SP, Brazil
| | | | - Geraldo Lorenzi-Filho
- Laboratorio do Sono, LIM 63, Divisão de Pneumologia, Instituto do Coraçao, InCor, Hospital das Clínicas HCFMUSP, Universidade de Sao Paulo, Eneas de Carvalho Aguiar 44, 8º andar, Sao Paulo, SP, 05403-900, Brazil.
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Liu Y, Wang M, Shi J. Influence of obstructive sleep apnoea on coronary artery disease in a Chinese population. J Int Med Res 2022; 50:3000605221115389. [PMID: 36036372 PMCID: PMC9434670 DOI: 10.1177/03000605221115389] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022] Open
Abstract
OBJECTIVE This study aimed to investigate the correlation between obstructive sleep apnoea (OSA) and the severity of coronary artery disease (CAD) assessed by angiography. METHODS This prospective study screened 273 patients diagnosed with CAD by coronary angiography. The severity of CAD was assessed by SYNTAX score. A total of 255 subjects were enrolled of whom 161 were diagnosed with OSA, with an apnoea-hypopnoea index ≥5/hour. Ninety-four CAD patients without OSA were used as controls. The relationship between OSA and CAD was analysed by multiple linear regression. RESULTS The prevalence of OSA in CAD patients was 63.1%. The prevalences of single-vessel, two-vessel, and three-vessel disease were similar in the two groups. However, CAD was significantly more severe in patients with OSA, measured by SYNTAX score, than in those without OSA. OSA was independently associated with CAD after adjusting for traditional risk factors. CONCLUSIONS OSA is relatively common among patients with CAD in China. The independent association between OSA and CAD, even after adjusting for traditional confounders, suggests that OSA should be taken into account when considering the risk factors for CAD. The present findings highlight the important adverse influence of OSA on the severity of CAD.
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Affiliation(s)
- Yufei Liu
- The First Affiliated Hospital of Harbin Medical University, No 23 Youzheng Street, Nangang District, Harbin, China
| | - Meitan Wang
- Harbin Children's Hospital affiliated to Harbin Medical University, Harbin, China
| | - Jinghui Shi
- The First Affiliated Hospital of Harbin Medical University, No 23 Youzheng Street, Nangang District, Harbin, China
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Zhang D, Ma Y, Xu J, Yi F. Association between obstructive sleep apnea (OSA) and atrial fibrillation (AF): A dose-response meta-analysis. Medicine (Baltimore) 2022; 101:e29443. [PMID: 35905270 PMCID: PMC9333485 DOI: 10.1097/md.0000000000029443] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/04/2023] Open
Abstract
BACKGROUND Refractory hypoxemia episodes are characteristic of obstructive sleep apnea (OSA). Patients with OSA suffer from oxidative stress in all systems. Atrial fibrillation (AF) is a type of arrhythmia that may be induced by OSA. In this study, we explored the dose-response relationship between OSA and AF. Our research provides the basis for a novel approach to AF prevention. METHODS We screened four databases (PubMed, Embase, the Cochrane Library, and Web of Science) for observational studies on OSA and AF. Studies were collected from database establishment to November 2020. We performed a traditional subgroup meta-analysis. Linear and spline dose-response models were applied to assess the association between the apnea-hypopnea index, an indicator of OSA severity, and the risk of AF. Review Manager version 5.3 software and Stata 16.0 were used for the analysis. RESULTS Sixteen observational studies were included in the study. We excluded a study from the conventional meta-analysis. In the subgroup analysis, the odds ratios for new onset AF for no obvious reason, new onset AF after surgical operations, such as coronary artery bypass grafting, and AF after ablation treatment were 1.71 (95% CI 1.37-2.13, P < .05), 2.65 (95% CI 2.32-3.01, P < .05), and 2.93 (95% CI 2.47-3.49, P < .05), respectively. Linear dose-response meta-analysis results revealed that the risk of AF increased with increasing apnea-hypopnea index value. CONCLUSION Through dose-response meta-analysis, we found a potential dose-response relationship between OSA severity and the risk of AF. This relationship should be considered in interventions aimed at AF prevention in the future.
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Affiliation(s)
- Dong Zhang
- Department of Cardiology, Xijing Hospital, The Air Force Military Medical University, Xi’an Shaanxi, China.Supplemental Digital Content is available for this article
| | - Yibo Ma
- Department of Cardiology, Xijing Hospital, The Air Force Military Medical University, Xi’an Shaanxi, China.Supplemental Digital Content is available for this article
| | - Jian Xu
- Department of Cardiology, Xijing Hospital, The Air Force Military Medical University, Xi’an Shaanxi, China.Supplemental Digital Content is available for this article
| | - Fu Yi
- Department of Cardiology, Xijing Hospital, The Air Force Military Medical University, Xi’an Shaanxi, China.Supplemental Digital Content is available for this article
- *Correspondence: Fu Yi, Department of Cardiology, Xijing Hospital, The Air Force Military Medical University, Xi’an Shaanxi 710032, China (e-mail: )
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Silva FSL, Furlanetto KC, Neves LMT, Cipriano GFB, Accioly MF, Viana-Júnior AB, Alves TB, Moraes WRA, Lima ACGB, Ribeiro KB, Sobreira-Neto MA, Leite CF. Translation, transcultural adaptation, and validation of the Brazilian Portuguese version of the Obstructive Sleep Apnea Knowledge and Attitudes (OSAKA) questionnaire. Sleep Breath 2022; 27:1195-1201. [DOI: 10.1007/s11325-022-02661-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2022] [Revised: 05/05/2022] [Accepted: 06/09/2022] [Indexed: 11/28/2022]
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Roberts R, Wall MJ, Braren I, Dhillon K, Evans A, Dunne J, Nyakupinda S, Huckstepp RTR. An Improved Model of Moderate Sleep Apnoea for Investigating Its Effect as a Comorbidity on Neurodegenerative Disease. Front Aging Neurosci 2022; 14:861344. [PMID: 35847678 PMCID: PMC9278434 DOI: 10.3389/fnagi.2022.861344] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2022] [Accepted: 04/19/2022] [Indexed: 11/25/2022] Open
Abstract
Sleep apnoea is a highly prevalent disease that often goes undetected and is associated with poor clinical prognosis, especially as it exacerbates many different disease states. However, most animal models of sleep apnoea (e.g., intermittent hypoxia) have recently been dispelled as physiologically unrealistic and are often unduly severe. Owing to a lack of appropriate models, little is known about the causative link between sleep apnoea and its comorbidities. To overcome these problems, we have created a more realistic animal model of moderate sleep apnoea by reducing the excitability of the respiratory network. This has been achieved through controlled genetically mediated lesions of the preBötzinger complex (preBötC), the inspiratory oscillator. This novel model shows increases in sleep disordered breathing with alterations in breathing during wakefulness (decreased frequency and increased tidal volume) as observed clinically. The increase in dyspnoeic episodes leads to reduction in REM sleep, with all lost active sleep being spent in the awake state. The increase in hypoxic and hypercapnic insults induces both systemic and neural inflammation. Alterations in neurophysiology, an inhibition of hippocampal long-term potentiation (LTP), is reflected in deficits in both long- and short-term spatial memory. This improved model of moderate sleep apnoea may be the key to understanding why this disorder has such far-reaching and often fatal effects on end-organ function.
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Affiliation(s)
- Reno Roberts
- School of Life Sciences, University of Warwick, Coventry, United Kingdom
| | - Mark J. Wall
- School of Life Sciences, University of Warwick, Coventry, United Kingdom
| | - Ingke Braren
- University Medical Center Eppendorf, Vector Facility, Institute for Experimental Pharmacology and Toxikology, Hamburg, Germany
| | - Karendeep Dhillon
- School of Life Sciences, University of Warwick, Coventry, United Kingdom
| | - Amy Evans
- School of Life Sciences, University of Warwick, Coventry, United Kingdom
| | - Jack Dunne
- School of Life Sciences, University of Warwick, Coventry, United Kingdom
| | | | - Robert T. R. Huckstepp
- School of Life Sciences, University of Warwick, Coventry, United Kingdom
- *Correspondence: Robert T. R. Huckstepp
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Zaremba S, Albus L, Hadjiathanasiou A, Vatter H, Wüllner U, Güresir E. Aneurysm size and blood pressure severity in patients with intracranial aneurysms and sleep apnea. J Clin Sleep Med 2022; 18:1539-1545. [PMID: 35088709 PMCID: PMC9163607 DOI: 10.5664/jcsm.9906] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2021] [Revised: 01/24/2022] [Accepted: 01/24/2022] [Indexed: 11/13/2022]
Abstract
STUDY OBJECTIVES Obstructive sleep apnea is a risk factor for hypertension. Hypertension is associated with aneurysm formation, growth, and rupture of intracranial aneurysm (IA). Retrospectively, symptoms of obstructive sleep apnea are more prevalent in patients with IAs. Studies investigating the prevalence and effect of objectively measured sleep apnea in these patients are sparse. We report on the baseline data of an ongoing prospective study. We cross-sectionally analyzed whether obstructive sleep apnea was associated with larger IAs and increased need for antihypertensive medications in a population of patients with unruptured IA. METHODS 130 adult (≥ 18 years) patients with unruptured IAs were recruited. Patients with ischemic stroke or intracranial hemorrhage within 3 months prior to screening were excluded. We assessed obstructive sleep apnea by full-night respiratory polygraphy. Aneurysm size and antihypertensive medication-as a surrogate parameter for the severity of hypertension-were compared between patients with and without obstructive sleep apnea (apnea-hypopnea index >5 events/h). Aneurysm growth and rupture rate were retrospectively analyzed. RESULTS 101 patients completed the study protocol. Obstructive sleep apnea was diagnosed in 68.0% (17) of male and 34.2% (26) of female participants and associated with more severe hypertension (1.536 ± 0.2 vs 0.74 ± 0.1 drugs; P = .01) and larger aneurysms (6.9 ± 1.0 vs 3.8 ± 0.5 mm; P = .01). CONCLUSIONS Patients with obstructive sleep apnea had more antihypertensive medication and larger IAs, probably due to accelerated aneurysm growth. Sleep apnea should be considered in patients with IAs. More research is needed to investigate the effects of sleep apnea on IAs and aneurysm outcome. CLINICAL TRIAL REGISTRATION Registry: ClinicalTrials.gov; Name: Incidence and Effects of Sleep Apnea on Intracerebral Aneurysms-IESA Study; URL: https://clinicaltrials.gov/ct2/show/NCT02880059; Identifier: NCT02880059. CITATION Zaremba S, Albus L, Hadjiathanasiou A, Vatter H, Wüllner U, Güresir E. Aneurysm size and blood pressure severity in patients with intracranial aneurysms and sleep apnea. J Clin Sleep Med. 2022;18(6):1539-1545.
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Affiliation(s)
- Sebastian Zaremba
- Department of Neurology, Rheinische Friedrich-Wilhelms-University, Bonn, Germany
- Clinic for Sleep Medicine, ZURZACHCare, Lucerne, Switzerland
| | - Luca Albus
- Department of Neurology, Rheinische Friedrich-Wilhelms-University, Bonn, Germany
| | | | - Hartmut Vatter
- Department of Neurosurgery, Rheinische Friedrich-Wilhelms-University, Bonn, Germany
| | - Ullrich Wüllner
- Department of Neurology, Rheinische Friedrich-Wilhelms-University, Bonn, Germany
- DZNE, German Centre for Neurodegenerative Diseases, Bonn, Germany
| | - Erdem Güresir
- Department of Neurosurgery, Rheinische Friedrich-Wilhelms-University, Bonn, Germany
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Li X, Wang X, Li W, Wang W. Increased carotid intima-media thickness is independently associated with the occurrence of depressive disorders in patients with obstructive sleep apnea without cardiocerebrovascular disease. J Psychiatr Res 2022; 150:122-129. [PMID: 35367656 DOI: 10.1016/j.jpsychires.2022.03.043] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/22/2021] [Revised: 02/16/2022] [Accepted: 03/24/2022] [Indexed: 11/19/2022]
Abstract
STUDY OBJECTIVES This study aimed to explore the relationship between carotid intima-media thickness (cIMT) and depression in patients with obstructive sleep apnea (OSA) without cardiocerebrovascular diseases. METHODS This study evaluated self-rating depression scale (SDS) scores, night sleep, and cIMT in 114 patients with OSA without cardiocerebrovascular diseases. RESULTS Among the 114 patients, 79.8% were male (mean age: 46.7 ± 11.58 years; range: 22-72 years). Moreover, 46.5%, 44.7%, and 7.89% of the patients presented with depressive disorders (8, 24, and 21 with severe, moderate, and mild degrees of depression, respectively), cIMT increase, and carotid plaques, respectively. Logistic regression with adjustment for age, sex, and other confounding factors revealed that, compared with patients with OSA without depressive disorders, those with depressive disorders had higher cIMT (odds ratio [OR] = 1.839; 95% confidence interval [CI]: 1.210-2.795), D-value (the difference between nocturnal mean blood oxygen saturation and the lowest blood oxygen saturation; OR = 1.434; 95% CI: 1.259-1.633]), and time spent at O2 saturation below 90% (OR = 1.060; 95% CI: 1.001-1.123). CONCLUSIONS cIMT and D-value are independently associated with depression in patients with OSA, which provides clinical evidence regarding the involvement of vascular damage in OSA-induced depression.
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Affiliation(s)
- Xiaomeng Li
- Institute of Respiratory Disease, The First Hospital of China Medical University, Shenyang, China
| | - Xingjian Wang
- Institute of Respiratory Disease, The First Hospital of China Medical University, Shenyang, China
| | - Wenyang Li
- Institute of Respiratory Disease, The First Hospital of China Medical University, Shenyang, China
| | - Wei Wang
- Institute of Respiratory Disease, The First Hospital of China Medical University, Shenyang, China.
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Lee S, Smith CE, Wallace ML, Andel R, Almeida DM, Patel SR, Buxton OM. Cardiovascular risks and sociodemographic correlates of multidimensional sleep phenotypes in two samples of US adults. SLEEP ADVANCES : A JOURNAL OF THE SLEEP RESEARCH SOCIETY 2022; 3:zpac005. [PMID: 35296108 PMCID: PMC8918427 DOI: 10.1093/sleepadvances/zpac005] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/15/2021] [Revised: 01/14/2022] [Indexed: 01/26/2023]
Abstract
Study Objectives Sleep is a modifiable risk factor for cardiovascular conditions. Holistic examination of within-person, multidimensional sleep patterns may offer more detailed information about the sleep-cardiovascular condition link, including who is more vulnerable to both. This study aimed to identify common sleep phenotypes in adulthood, establish the validity of the phenotypes in relation to cardiovascular conditions, and explore sociodemographic and background characteristics of the phenotypes. Methods Across two independent samples of adults (N 1 = 4600; N 2 = 2598) from the Midlife in the United States Study, latent class analysis (LCA) extracted sleep phenotypes using five key self-reported sleep dimensions. Log-binomial regression was used to determine whether sleep phenotypes differentially predicted cardiovascular conditions, adjusting for known risk factors. LCA with covariates was used to compare sociodemographic characteristics of the identified sleep phenotypes. Results Four sleep phenotypes were identified consistently across the two samples: good sleepers, nappers, dissatisfied/inefficient sleepers, and irregular sleepers. Compared to good sleepers (reference), dissatisfied/inefficient sleepers exhibited a higher risk of cardiovascular conditions in both samples (RR Sample1: 29%, RR Sample2: 53%) and consisted of relatively more racial/ethnic minorities. Nappers exhibited a higher risk of cardiovascular conditions in one sample (RR Sample1: 38%) and consisted of more women and older adults. Irregular sleepers exhibited no significantly different cardiovascular risk and were relatively younger. Conclusions Common sleep phenotypes in adulthood exhibit differential risks for cardiovascular conditions. Cooccurring sleep dissatisfaction and inefficiency, in particular, may relate to increased risk of cardiovascular conditions. Certain sociodemographic groups (racial minorities, women, older adults) disproportionately fit within high-risk sleep phenotypes.
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Affiliation(s)
- Soomi Lee
- University of South Florida, School of Aging Studies, Tampa, FL, USA,Corresponding author. Soomi Lee, Assistant Professor, School of Aging Studies, University of South Florida, 4202 E. Fowler Avenue, MHC 1344, Tampa, FL 33620, USA.
| | - Claire E Smith
- University of South Florida, School of Aging Studies, Tampa, FL, USA
| | | | - Ross Andel
- University of South Florida, School of Aging Studies, Tampa, FL, USA
| | - David M Almeida
- The Pennsylvania State University, Department of Human Development and Family Studies, State College, PA, USA
| | - Sanjay R Patel
- University of Pittsburgh, Department of Medicine, Pittsburgh, PA, USA
| | - Orfeu M Buxton
- The Pennsylvania State University, Department of Biobehavioral Health, State College, PA, USA
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Lavie L, Si-On E, Hoffman A. Markers of Carotid Plaque Destabilization in Patients With Sleep-Disordered Breathing. Front Neurol 2022; 13:811916. [PMID: 35250817 PMCID: PMC8888822 DOI: 10.3389/fneur.2022.811916] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2021] [Accepted: 01/14/2022] [Indexed: 11/25/2022] Open
Abstract
Sleep-disordered breathing (SDB) is a nightly respiratory condition characterized by intermittent hypoxia, leading to oxidative stress, inflammation, and atherosclerosis. However, most cellular markers of human carotid plaques in SDB have not yet been assessed. We aimed at characterizing the cellular, inflammatory, and nitro-oxidative stress markers in carotid plaques obtained from 25 patients undergoing endarterectomy and screened for SDB. Sleep studies were performed during their preoperative hospitalization night using the Watch-PAT 100 device. Oxygen desaturation index (ODI) was used for dividing patients into two groups. Fourteen patients with ODI >5 were designated as SDB and 11 patients with ODI ≤ 5 as non-SDB. Demographics, comorbidities, cardiovascular risk factors, and medications were recorded. Cellular markers in plaques were analyzed by immunofluorescence using confocal microscopy. The expression of neutrophils was identified by CD66b+ and neutrophil elastase, macrophage-foam cells were identified by CD163+, and scavenger receptors by CD68+ and CD36+ expression. Additional markers included 3-nitrotyrosine, endothelial CD31, and smooth muscle cell-actin (SMC-actin). Plaques' lipids were determined by immunohistochemistry with Oil Red O staining. Notably, significantly higher values were found for SDB as compared to patients with non-SDB for 3-nitrotyrosine (p <0.004) and intracellular lipids' content (p <0.02), whereas SMC-actin was lower (p <0.006). There were no significant differences between patients with carotid-associated symptoms (symptomatic) and patients without carotid-associated symptoms (asymptomatic). However, a sub-group of symptomatic patients with co-existent SDB expressed the highest 3-nitrotyrosin, and intracellular lipids levels, and the lowest SMC-actin levels, whereas non-SDB/asymptomatic patients expressed the lowest 3-nitrotyrosin and lipids levels and the highest SMS-actin levels among all patients. Accordingly, ODI was lowest in non-SDB/asymptomatic patients and highest in SDB/symptomatic. In conclusion, plaques of patients with SDB were characterized by markedly increased levels of 3-nitrotyrosine and intracellular lipids content. Conversely, SMC-actin levels were significantly lower. These three markers, such as increased 3-nitrotyrosine and intracellular lipids and decreased SMC-actin are associated with plaque vulnerability and instability. These findings are in line with earlier reports demonstrating increased intima-media thickness in large cohorts of sleep apnea and patients with SDB, and thus, may indicate a higher susceptibility to plaque vulnerability and rapture in patients with SDB.
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Affiliation(s)
- Lena Lavie
- Unit of Anatomy and Cell Biology, The Ruth and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel
- *Correspondence: Lena Lavie
| | - Erez Si-On
- Department of Vascular Surgery and Transplantation, Rambam Health Care Campus, The Ruth and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel
| | - Aaron Hoffman
- Department of Vascular Surgery and Transplantation, Rambam Health Care Campus, The Ruth and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel
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Venema JAMU, Vries GEKD, van Goor H, Westra J, Hoekema A, Wijkstra PJ. Cardiovascular and metabolic effects of a mandibular advancement device and continuous positive airway pressure in moderate obstructive sleep apnea: a randomized controlled trial. J Clin Sleep Med 2022; 18:1547-1555. [PMID: 35088708 DOI: 10.5664/jcsm.9908] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
STUDY OBJECTIVES It has been suggested that treatment for obstructive sleep apnea (OSA) reduces cardiovascular risk. So far, knowledge is limited about the difference in the reduction of this risk between mandibular advancement device (MAD) and continuous positive airway pressure (CPAP) therapy. The aim of this study was to compare the cardiovascular effects of MAD versus CPAP therapy in patients with moderate OSA. METHODS Patients with an apnea-hypopnea index (AHI) of 15-30 events/h were randomized to either MAD or CPAP therapy. At baseline and after 12-months follow-up, 24-hour ambulant blood pressure measurements (ABPM) and laboratory measurements were performed. ABPM consisted of 24-hour, daytime and night-time systolic (SBP) and diastolic blood pressure (DBP), and heart rate (HR) measurements. Laboratory measurements consisted of serum lipid values, creatinine, high-sensitivity c-reactive protein, plasma glucose, hemoglobin A1c (HbA1c), proinflammatory cytokines, soluble receptor for advanced glycation end products (sRAGE), chemokines and adhesion molecules. RESULTS Of the 85 randomized patients with moderate OSA, data were available for 54 patients (n=24 MAD, n=30 CPAP) at 12-month follow-up and showed that AHI significantly decreased with either therapy. In the MAD group, sRAGE and HbA1c were significantly higher after 12 months follow-up compared to baseline. No significant changes were found between MAD and CPAP treatment for all outcomes. CONCLUSIONS Treatment of patients with moderate OSA with either MAD or CPAP therapy had no profound effects on major cardiovascular risk factors after 12-months. CLINICAL TRIAL REGISTRATION Registry: ClinicalTrials.gov; Title: MRA Therapy Versus CPAP Therapy in Moderate OSAS; Identifier: NCT01588275; URL: https://clinicaltrials.gov/ct2/show/NCT01588275.
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Affiliation(s)
- Julia A M Uniken Venema
- Department of Orofacial Pain and Dysfunction, Academic Centre for Dentistry Amsterdam, University of Amsterdam and Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.,Department of Oral and Maxillofacial Surgery, Amsterdam University Medical Centre, location Academic Medical Center (AMC), and Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam and Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
| | - Grietje E Knol-de Vries
- Department of Pulmonary Diseases, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.,Groningen Research Institute for Asthma and COPD, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.,Department of General Practice and Elderly Care Medicine, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Harry van Goor
- Department of Pathology and Medical Biology, University Medical Center Groningen, Groningen, the Netherlands
| | - Johanna Westra
- Department of Rheumatology and Clinical Immunology, University Medical Center Groningen, Groningen, the Netherlands
| | - Aarnoud Hoekema
- Department of Orofacial Pain and Dysfunction, Academic Centre for Dentistry Amsterdam, University of Amsterdam and Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.,Department of Oral and Maxillofacial Surgery, Amsterdam University Medical Centre, location Academic Medical Center (AMC), and Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam and Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.,Department of Oral and Maxillofacial Surgery, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.,Department of Oral and Maxillofacial Surgery, Tjongerschans Hospital, Heerenveen, The Netherlands
| | - Peter J Wijkstra
- Department of Pulmonary Diseases, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.,Groningen Research Institute for Asthma and COPD, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.,Center for Home Mechanical Ventilation, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
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LncRNA XR_596701 protects H9c2 cells against intermittent hypoxia-induced injury through regulation of the miR-344b-5p/FAIM3 axis. Cell Death Dis 2022; 8:42. [PMID: 35091561 PMCID: PMC8799738 DOI: 10.1038/s41420-022-00834-8] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2021] [Revised: 12/31/2021] [Accepted: 01/13/2022] [Indexed: 11/23/2022]
Abstract
Long noncoding RNAs (lncRNAs) participate in various biological processes and cardiovascular diseases. Recently, a novel lncRNA XR_596701 was found to be differentially expressed in obstructive sleep apnea (OSA)-induced myocardial tissue compared to normal myocardial tissues. However, the pathological effect and regulatory mechanism of XR_596701 in intermittent hypoxia (IH)-mediated cardiomyocytes damage have not been studied. The subcellular localization of XR_596701 was determined by fluorescence in situ hybridization (FISH). Gene expressions of XR_596701 and miR-344b-5p were detected by quantitative real-time polymerase chain reaction (qRT-PCR) in IH-induced H9c2 cells. Cell proliferation was measured by 5-ethynyl-2′-deoxyuridine (EdU) staining assay. Cell apoptosis was detected by Hoechst 33342/PI staining and immunofluorescence (IF). Apoptotic protein of H9c2 cells was measured by western blot. The direct interaction between XR_596701 and miR-344b-5p as well as miR-344b-5p and Fas apoptotic inhibitory molecule 3 (FAIM3) were examined using dual-luciferase reporter assay. The significance of XR_596701 and miR-344b-5p on cell proliferation and apoptosis was evaluated by using gain-of-function and loss-of-function approaches. XR_596701 was upregulated, while miR-344b-5p downregulated in IH-induced H9c2 cells. Functionally, suppression of XR_596701 and overexpression of miR-344b-5p inhibited cell proliferation and promoted cell apoptosis in H9c2 cells. The roles of XR_596701 were achieved by sponging miR-344b-5p. And the function of miR-344b-5p was reversed by targeting FAIM3. Additionally, FAIM3 mediated IH-induced H9c2 cells damage by XR_596701. XR_596701 was serve as a novel lncRNA that indicated protective roles on proliferation and apoptosis of IH-induced H9c2 cells through the miR-344b-5p/FAIM3 axis.
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Long non-coding RNA MALAT1 affects intermittent hypoxia-induced endothelial injury by regulating miR-142-3p/HMGB1. Sleep Breath 2022; 26:2015-2024. [DOI: 10.1007/s11325-021-02545-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2021] [Revised: 11/29/2021] [Accepted: 11/30/2021] [Indexed: 11/27/2022]
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Lévy P, Naughton MT, Tamisier R, Cowie MR, Bradley TD. Sleep Apnoea and Heart Failure. Eur Respir J 2021; 59:13993003.01640-2021. [PMID: 34949696 DOI: 10.1183/13993003.01640-2021] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2021] [Accepted: 09/07/2021] [Indexed: 11/05/2022]
Abstract
Heart Failure (HF) and Sleep-Disordered-Breathing (SDB) are two common conditions that frequently overlap and have been studied extensively in the past three decades. Obstructive Sleep Apnea (OSA) may result in myocardial damage, due to intermittent hypoxia increased sympathetic activity and transmural pressures, low-grade vascular inflammation and oxidative stress. On the other hand, central sleep apnoea and Cheyne-Stokes respiration (CSA-CSR) occurs in HF, irrespective of ejection fraction either reduced (HFrEF), preserved (HFpEF) or mildly reduced (HFmrEF). The pathophysiology of CSA-CSR relies on several mechanisms leading to hyperventilation, breathing cessation and periodic breathing. Pharyngeal collapse may result at least in part from fluid accumulation in the neck, owing to daytime fluid retention and overnight rostral fluid shift from the legs. Although both OSA and CSA-CSR occur in HF, the symptoms are less suggestive than in typical (non-HF related) OSA. Overnight monitoring is mandatory for a proper diagnosis, with accurate measurement and scoring of central and obstructive events, since the management will be different depending on whether the sleep apnea in HF is predominantly OSA or CSA-CSR. SDB in HF are associated with worse prognosis, including higher mortality than in patients with HF but without SDB. However, there is currently no evidence that treating SDB improves clinically important outcomes in patients with HF, such as cardiovascular morbidity and mortality.
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Affiliation(s)
- Patrick Lévy
- Univ Grenoble Alpes, Inserm, HP2 laboratory, Grenoble, France .,CHU Grenoble Alpes, Physiology, EFCR, Grenoble, France.,All authors contributed equally to the manuscript
| | - Matt T Naughton
- Alfred Hospital, Department of Respiratory Medicine and Monash University, Melbourne, Australia.,All authors contributed equally to the manuscript
| | - Renaud Tamisier
- Univ Grenoble Alpes, Inserm, HP2 laboratory, Grenoble, France.,CHU Grenoble Alpes, Physiology, EFCR, Grenoble, France.,All authors contributed equally to the manuscript
| | - Martin R Cowie
- Royal Brompton Hospital and Faculty of Lifesciences & Medicine, King"s College London, London, UK.,All authors contributed equally to the manuscript
| | - T Douglas Bradley
- Sleep Research Laboratory of the University Health Network Toronto Rehabilitation Institute, Centre for Sleep Medicine and Circadian Biology of the University of Toronto and Department of Medicine of the University Health Network Toronto General Hospital, Canada.,All authors contributed equally to the manuscript
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Smith DF, Schuler CL, Hossain MM, Huang G, McConnell K, Urbina EM, Amin RS. Early Atherosclerotic Inflammatory Pathways in Children with Obstructive Sleep Apnea. J Pediatr 2021; 239:168-174. [PMID: 34450122 PMCID: PMC9020582 DOI: 10.1016/j.jpeds.2021.08.031] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/24/2021] [Revised: 07/15/2021] [Accepted: 08/18/2021] [Indexed: 12/21/2022]
Abstract
OBJECTIVE To evaluate structural and functional carotid changes and inflammatory profiles in children with obstructive sleep apnea (OSA) and healthy controls. STUDY DESIGN Patients with OSA and matched controls (ages 5-13 years) were recruited. Proinflammatory cytokines and acute phase reactants were measured at 6:00 p.m. Common carotid artery measures were determined using ultrasound. Confirmatory factor analysis was used to determine subgroups of cytokines and their effects on carotid measures. RESULTS Ninety-six patients participated (53 healthy controls, 43 patients with OSA). OSA was associated with increased proinflammatory cytokines (cluster of differentiation-40 ligand [CD40-L], interleukin [IL]-6, and IL-8) and high sensitivity C-reactive protein (P < .05 for all). One cytokine subgroup (IL-6 and IL-8) was negatively associated with markers of carotid function, indicating reduced arterial distensibility and increased stiffness (P < .05 for 3 ultrasound measures); and tumor necrosis factor-α had an opposing effect on carotid function compared with this cytokine subgroup (P < .05 for 2 ultrasound measures). Linear regression demonstrated significant associations between and tumor necrosis factor- α and 2 measures of carotid function (P < .05 for each). Children with OSA did not have functional or structural carotid changes compared with controls. CONCLUSION OSA was not directly associated with structural and functional carotid changes but was associated with upregulation of key proinflammatory cytokines (sCD40-L, IL-6, and IL-8). Together, IL-6 and IL-8 were associated with changes in carotid function. Longitudinal studies are needed to demonstrate that the inflammatory milieu observed in our population is a precursor of atherosclerosis in children.
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Affiliation(s)
- David F Smith
- Division of Pediatric Otolaryngology-Head and Neck Surgery, Cincinnati Children's Hospital Medical Center, Cincinnati, OH; Division of Pulmonary Medicine and the Sleep Center, Cincinnati Children's Hospital Medical Center, Cincinnati, OH; The Center for Circadian Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, OH; Department of Otolaryngology-Head and Neck Surgery, University of Cincinnati College of Medicine, Cincinnati, OH
| | - Christine L Schuler
- Division of Pulmonary Medicine and the Sleep Center, Cincinnati Children's Hospital Medical Center, Cincinnati, OH; Division of Hospital Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, OH; Department of Pediatrics, Cincinnati Children's Hospital Medical Center and University of Cincinnati, Cincinnati, OH
| | - Md M Hossain
- Department of Pediatrics, Cincinnati Children's Hospital Medical Center and University of Cincinnati, Cincinnati, OH; Division of Biostatistics and Epidemiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH
| | - Guixia Huang
- Division of Biostatistics and Epidemiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH
| | - Keith McConnell
- Division of Pulmonary Medicine and the Sleep Center, Cincinnati Children's Hospital Medical Center, Cincinnati, OH
| | - Elaine M Urbina
- Department of Pediatrics, Cincinnati Children's Hospital Medical Center and University of Cincinnati, Cincinnati, OH; The Heart Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH
| | - Raouf S Amin
- Division of Pulmonary Medicine and the Sleep Center, Cincinnati Children's Hospital Medical Center, Cincinnati, OH; Department of Pediatrics, Cincinnati Children's Hospital Medical Center and University of Cincinnati, Cincinnati, OH.
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Yang CC, Lee KW, Watanabe K, Kawakami N. The association between shift work and possible obstructive sleep apnea: a systematic review and meta-analysis. Int Arch Occup Environ Health 2021; 94:1763-1772. [PMID: 33677677 PMCID: PMC8490216 DOI: 10.1007/s00420-021-01675-1] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2020] [Accepted: 02/16/2021] [Indexed: 11/16/2022]
Abstract
BACKGROUND Shift work is a workschedule, since industrial era and some employees work in shift. It causes a desynchronization of the biological clock with consequences on sleep amount and quality, such as insomnia and easy fatigue. Obstructive sleep apnea (OSA) is one of the sleep problems that are getting more and more attention, but studies on the association between shift work and OSA were rare. Herein, we aimed to conduct a systematic review and meta-analysis to investigate the association between shift work and possible OSA. METHODS This study was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We queried PubMed, Embase, and Web of Science databases using a related set of keywords. The inclusion criteria were as follows: (1) participants were adult employees hired by a company or organization; (2) exposure was shift work; and (3) outcome was possible OSA according to examination or assessment. RESULTS We included six studies in the systematic review and five studies were selected for further meta-analysis. A random-effects model showed an association of shift work with a small, non-significant increase in possible OSA cases (pooled prevalence relative risk = 1.05; 95% CI 0.85-1.30; p = 0.65). This association occurred in both healthcare and non-healthcare workers group. CONCLUSION The association between shift work and possible OSA remains inconclusive and could be small if not negligible. Future studies should assess the association between specific work schedules and specific OSA definitions. TRIAL REGISTRATION NUMBER PROSPERO ID: CRD42020156837.
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Affiliation(s)
- Chen-Cheng Yang
- Department of Occupational and Environmental Medicine, Kaohsiung Municipal Siaogang Hospital, No. 482, Shanming Road, Siaogang District, Kaohsiung City, Taiwan.
- Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
- Department of Family Medicine, Kaohsiung Municipal Siaogang Hospital, Kaohsiung, Taiwan.
- Department of Occupational and Environmental Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
- Department of Mental Health, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
- Environmental and Occupational Medicine Center, Kaohsiung Municipal Siaogang Hospital, Kaohsiung, Taiwan.
| | - Kuo-Wei Lee
- Department of Neurology, Kaohsiung Municipal Siaogang Hospital, Kaohsiung, Taiwan
| | - Kazuhiro Watanabe
- Department of Mental Health, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Norito Kawakami
- Department of Mental Health, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
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