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17 pages, 2059 KiB

Open AccessArticle

Adipokines and Inflammatory Markers in Acute Myocardial Infarction Patients with and without Obstructive Sleep Apnea: A Comparative Analysis

by Ana L. Vega-Jasso, Luis M. Amezcua-Guerra, Héctor González-Pacheco, Julio Sandoval-Zárate, César A. González-Díaz, Jennifer Escobar-Alvarado, Jennifer D. Manzano-Luna and Malinalli Brianza-Padilla

Int. J. Mol. Sci. 2023, 24(19), 14674; https://doi.org/10.3390/ijms241914674 - 28 Sep 2023

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Abstract

An association has been suggested between acute myocardial infarction (AMI) and obstructive sleep apnea (OSA). Considering the role of adipose-tissue-derived inflammatory mediators (adipokines) and the shared risk factor of obesity in OSA and AMI, this study aimed to investigate the involvement of adipokines [...] Read more.

An association has been suggested between acute myocardial infarction (AMI) and obstructive sleep apnea (OSA). Considering the role of adipose-tissue-derived inflammatory mediators (adipokines) and the shared risk factor of obesity in OSA and AMI, this study aimed to investigate the involvement of adipokines in AMI patients with and without OSA. Serum levels of adipokines and inflammatory mediators were quantified, and home respiratory polygraphy was conducted. A total of 30 AMI patients and 25 controls were included. Patients with AMI exhibited elevated levels of resistin (7.4 vs. 3.7 ng/mL), interleukin-6 (8.8 vs. 1.3 pg/mL), and endothelin-1 (3.31 vs. 1.8 pg/mL). Remarkably, AMI patients with concomitant OSA exhibited higher levels of resistin (7.1 vs. 3.7 ng/mL), interleukin-6 (8.9 vs. 1.3 pg/mL), endothelin-1 (3.2 vs. 1.8 pg/mL), creatin kinase (1430 vs. 377 U/L), creatine kinase-MB (64.6 vs. 9.7 ng/mL), and troponin T (2298 vs. 356 pg/mL) than their non-OSA counterparts. Leptin showed a correlation with OSA severity markers. OSA was associated with greater cardiac damage in AMI patients. Our findings underscore that adipokines alone are not sufficient to discriminate the risk of AMI in the presence of OSA. Further research is necessary to determine the potential mechanisms contributing to exacerbated cardiac damage in patients with both conditions. Full article

(This article belongs to the Special Issue Sleep Apnea and Systemic Inflammation)

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19 pages, 2343 KiB

Open AccessArticle

Investigating the Role of Serum and Plasma IL-6, IL-8, IL-10, TNF-alpha, CRP, and S100B Concentrations in Obstructive Sleep Apnea Diagnosis

by Piotr Fiedorczuk, Ewa Olszewska, Agnieszka Polecka, Marzena Walasek, Barbara Mroczko and Agnieszka Kulczyńska-Przybik

Int. J. Mol. Sci. 2023, 24(18), 13875; https://doi.org/10.3390/ijms241813875 - 09 Sep 2023

Cited by 2 | Viewed by 1070

Abstract

Obstructive sleep apnea (OSA) is a prevalent and underdiagnosed condition associated with cardiovascular diseases, depression, accidents, and stroke. There is an increasing need for alternative diagnostic tools beyond overnight sleep studies that measure the Apnea/Hypopnea Index (AHI). In this single-center, case-control study, we [...] Read more.

Obstructive sleep apnea (OSA) is a prevalent and underdiagnosed condition associated with cardiovascular diseases, depression, accidents, and stroke. There is an increasing need for alternative diagnostic tools beyond overnight sleep studies that measure the Apnea/Hypopnea Index (AHI). In this single-center, case-control study, we evaluated serum and plasma concentrations of IL-6, IL-8, IL-10, TNF-α, CRP, and S100B in 80 subjects, including 52 OSA patients (27 moderate [15 ≤ AHI ˂ 30], 25 severe [AHI ≥ 30]) and 28 non-OSA controls (AHI 0-5). Participants with OSA showed approximately 2 times higher median concentrations of CRP in plasma, and IL-6 in serum, as well as 1.3 to 1.7 times higher concentrations of TNF-α and IL-8 in plasma compared with the control group. Receiver Operator Characteristic (ROC) curve analysis was performed to evaluate the predictive capabilities of these serum and plasma biomarkers in distinguishing between the OSA and control groups, revealing varying sensitivity and specificity. In summary, in this study, serum and plasma biomarkers CRP, S100B, IL-6, TNF-α, and IL-8 have been shown to be elevated in patients with OSA, correlated positively with disease severity, age, and BMI. These results support the potential role of these biomarkers in diagnosing OSA, supplementing traditional methods such as overnight sleep studies. Full article

(This article belongs to the Special Issue Sleep Apnea and Systemic Inflammation)

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15 pages, 1308 KiB

Open AccessArticle

SMAD4 Expression in Monocytes as a Potential Biomarker for Atherosclerosis Risk in Patients with Obstructive Sleep Apnea

by Elena Díaz-García, Aldara García-Sánchez, David Sánz-Rubio, Enrique Alfaro, Cristina López-Fernández, Raquel Casitas, Eva Mañas Baena, Irene Cano-Pumarega, Pablo Cubero, Marta Marin-Oto, Eduardo López-Collazo, José María Marin, Francisco García-Río and Carolina Cubillos-Zapata

Int. J. Mol. Sci. 2023, 24(9), 7900; https://doi.org/10.3390/ijms24097900 - 26 Apr 2023

Cited by 1 | Viewed by 1589

Abstract

Obstructive sleep apnea (OSA) patients are at special risk of suffering atherosclerosis, leading to major cardiovascular diseases. Notably, the transforming growth factor (TGF-β) plays a crucial role in the development and progression of atherosclerosis. In this context, the central regulator of TGF-β pathway, [...] Read more.

Obstructive sleep apnea (OSA) patients are at special risk of suffering atherosclerosis, leading to major cardiovascular diseases. Notably, the transforming growth factor (TGF-β) plays a crucial role in the development and progression of atherosclerosis. In this context, the central regulator of TGF-β pathway, SMAD4 (small mother against decapentaplegic homolog 4), has been previously reported to be augmented in OSA patients, which levels were even higher in patients with concomitant cardiometabolic diseases. Here, we analyzed soluble and intracellular SMAD4 levels in plasma and monocytes from OSA patients and non-apneic subjects, with or without early subclinical atherosclerosis (eSA). In addition, we used in vitro and ex vivo models to explore the mechanisms underlying SMAD4 upregulation and release. Our study confirmed elevated sSMAD4 levels in OSA patients and identified that its levels were even higher in those OSA patients with eSA. Moreover, we demonstrated that SMAD4 is overexpressed in OSA monocytes and that intermittent hypoxia contributes to SMAD4 upregulation and release in a process mediated by NLRP3. In conclusion, this study highlights the potential role of sSMAD4 as a biomarker for atherosclerosis risk in OSA patients and provides new insights into the mechanisms underlying its upregulation and release to the extracellular space. Full article

(This article belongs to the Special Issue Sleep Apnea and Systemic Inflammation)

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17 pages, 2198 KiB

Open AccessArticle

Osteoprotegerin, Chitinase 3-like Protein 1, and Cardiotrophin-1 as Potential Biomarkers of Obstructive Sleep Apnea in Adults—A Case-Control Study

by Piotr Fiedorczuk, Ewa Olszewska, Joanna Rogalska and Małgorzata M. Brzóska

Int. J. Mol. Sci. 2023, 24(3), 2607; https://doi.org/10.3390/ijms24032607 - 30 Jan 2023

Cited by 5 | Viewed by 1734

Abstract

Obstructive sleep apnea (OSA) is a prevalent, underdiagnosed disease and is considered a risk factor for cardiovascular diseases, depression, accidents, and stroke. Recent clinical practice guidelines for OSA expressed the need for a new clinical tool that establishes the Apnea–Hypopnea Index (AHI) to [...] Read more.

Obstructive sleep apnea (OSA) is a prevalent, underdiagnosed disease and is considered a risk factor for cardiovascular diseases, depression, accidents, and stroke. Recent clinical practice guidelines for OSA expressed the need for a new clinical tool that establishes the Apnea–Hypopnea Index (AHI) to determine the disease burden. The serum and plasma concentrations of Osteoprotegerin (OPG), Chitinase 3-like protein 1 (YKL-40), and Cardiotrophin-1 (CT-1) in 80 subjects—52 OSA patients, 27 moderate (15 ≤ AHI ˂ 30) and 25 severe (AHI ≥ 30), and 28 non-OSA controls (AHI 0–5)—were determined. Moreover, the Total Oxidative Status (TOS), Total Antioxidative Status (TAS), and Oxidative Stress Index (OSI) were assessed in the serum and plasma to evaluate whether the severity of OSA and the concentrations of OPG, YKL-40, and CT-1 correlate with the oxidative/reductive status. The serum and plasma concentrations of YKL-40 and CT-1 were higher in the OSA group, whereas the serum and plasma concentrations of OPG were lower compared to the control group. The concentrations of OPG, YKL-40, and CT-1 in the serum and plasma correlated with AHI; however, a better correlation of the concentrations was obtained for the above-mentioned proteins in the plasma. The concentrations of YKL-40 and CT-1 in the serum and OPG in the plasma show better diagnostic capabilities for moderate and severe OSA than the concentrations of YKL-40 and CT-1 in the plasma and the concentrations of OPG in the serum. Full article

(This article belongs to the Special Issue Sleep Apnea and Systemic Inflammation)

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16 pages, 613 KiB

Open AccessArticle

A Case-Control Study on the Changes in High-Sensitivity C-Reactive Protein and Tumor Necrosis Factor-Alpha Levels with Surgical Treatment of OSAS

by Ewa Olszewska, Tymoteusz Marek Pietrewicz, Magdalena Świderska, Jacek Jamiołkowski and Adrian Chabowski

Int. J. Mol. Sci. 2022, 23(22), 14116; https://doi.org/10.3390/ijms232214116 - 15 Nov 2022

Cited by 8 | Viewed by 1226

Abstract

Obstructive sleep apnea syndrome (OSAS) is a common but underdiagnosed condition with significant health and economic implications for society. Inflammatory mediators are proposed to be associated with the presence and severity of OSAS and contribute to morbidity and mortality. This paper details a [...] Read more.

Obstructive sleep apnea syndrome (OSAS) is a common but underdiagnosed condition with significant health and economic implications for society. Inflammatory mediators are proposed to be associated with the presence and severity of OSAS and contribute to morbidity and mortality. This paper details a prospective non-randomized case control study of a cohort of subjects, who underwent surgical treatment of OSAS and were enrolled to assess the sleep parameters and blood levels of selected inflammatory markers at pre-operative and post-operative time points, also comparing them to the levels in a control group. A total of 25 study subjects and 18 control subjects were enrolled. Median values and interquartile range (IQR) of the apnea–hypopnea index (AHI) in the study group pre-operatively and post-operatively were 34 (18.5–45.5) and 13.3 (7.5–27.3), while in the control group 1.4 (1.0–2.1) per hour. The mean (IQR) hs-CRP levels (mg/L) were 1.782 (0.941–5.594) and 1.980 (0.990–5.445) in the study group, pre-operatively and post-operatively, respectively, while 0.891 (0.767–1.436) in the control group. The mean (IQR) TNF-α levels (pg/mL) were 7.999 (6.137–9.216) and 6.614 (5.534–7.460) pre-and post-operatively, respectively, and were 6.000 (5.026–6.823) in the control group. Results demonstrated that both inflammatory markers, hs-CRP and TNF-α, are higher in subjects with OSAS compared to the controls, and their levels decrease, but are still higher than the controls, after successful surgical treatment. Further analysis including the body mass index and age demonstrated that these changes were significant for TNF-α, but not hs-CRP. Full article

(This article belongs to the Special Issue Sleep Apnea and Systemic Inflammation)

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18 pages, 2312 KiB

Open AccessArticle

CPAP Influence on Readily Available Inflammatory Markers in OSA—A Pilot Study

by Ioana Madalina Zota, Cristina Andreea Adam, Dragoș Traian Marius Marcu, Cristian Stătescu, Radu Sascău, Larisa Anghel, Daniela Boișteanu, Mihai Roca, Corina Lucia Dima Cozma, Alexandra Maștaleru, Maria Magdalena Leon Constantin, Elena Andreea Moaleș and Florin Mitu

Int. J. Mol. Sci. 2022, 23(20), 12431; https://doi.org/10.3390/ijms232012431 - 17 Oct 2022

Cited by 3 | Viewed by 1893

Abstract

Obstructive sleep apnea (OSA) is characterized by repetitive upper airway collapse, chronic hypoxia and a proinflammatory phenotype. The purpose of our study was to evaluate readily available inflammatory biomarkers (C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), white blood cell count (WBC), red cell [...] Read more.

Obstructive sleep apnea (OSA) is characterized by repetitive upper airway collapse, chronic hypoxia and a proinflammatory phenotype. The purpose of our study was to evaluate readily available inflammatory biomarkers (C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), white blood cell count (WBC), red cell distribution width (RDW), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), mean platelet volume (MPV), WBC-to-MPV ratio (WMR) and lymphocyte-to-C-reactive protein ratio (LCR)) before and after CPAP in patients with moderate–severe OSA. We performed a prospective study that included patients with newly-diagnosed moderate–severe OSA. The control groups (patients without OSA and with mild OSA) were selected from the hospital polygraphy database. All subjects underwent routine blood panel, which was repeated in moderate–severe OSA patients after 8 weeks of CPAP. Our final study group included 31 controls, 33 patients with mild, 22 patients with moderate and 37 patients with severe OSA. CRP, ESR, NLR and WMR were correlated with OSA severity. After 8-week CPAP therapy, we documented a decrease in weight status, which remained statistically significant in both CPAP-adherent and non-adherent subgroups. Readily available, inexpensive inflammatory parameters can predict the presence of moderate–severe OSA, but are not influenced by short-term CPAP. Full article

(This article belongs to the Special Issue Sleep Apnea and Systemic Inflammation)

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12 pages, 1984 KiB

Open AccessArticle

Obstructive Sleep Apnea Syndrome In Vitro Model: Controlled Intermittent Hypoxia Stimulation of Human Stem Cells-Derived Cardiomyocytes

by Danielle Regev, Sharon Etzion, Hen Haddad, Jacob Gopas and Aviv Goldbart

Int. J. Mol. Sci. 2022, 23(18), 10272; https://doi.org/10.3390/ijms231810272 - 07 Sep 2022

Cited by 4 | Viewed by 1872

Abstract

Cardiovascular morbidity is the leading cause of death of obstructive sleep apnea (OSA) syndrome patients. Nocturnal airway obstruction is associated with intermittent hypoxia (IH). In our previous work with cell lines, incubation with sera from OSA patients induced changes in cell morphology, NF-κB [...] Read more.

Cardiovascular morbidity is the leading cause of death of obstructive sleep apnea (OSA) syndrome patients. Nocturnal airway obstruction is associated with intermittent hypoxia (IH). In our previous work with cell lines, incubation with sera from OSA patients induced changes in cell morphology, NF-κB activation and decreased viability. A decrease in beating rate, contraction amplitude and a reduction in intracellular calcium signaling was also observed in human cardiomyocytes differentiated from human embryonic stem cells (hESC-CMs). We expanded these observations using a new controlled IH in vitro system on beating hESC-CMs. The Oxy-Cycler system was programed to generate IH cycles. Following IH, we detected the activation of Hif-1α as an indicator of hypoxia and nuclear NF-κB p65 and p50 subunits, representing pro-inflammatory activity. We also detected the secretion of inflammatory cytokines, such as MIF, PAI-1, MCP-1 and CXCL1, and demonstrated a decrease in beating rate of hESC-CMs following IH. IH induces the co-activation of inflammatory features together with cardiomyocyte alterations which are consistent with myocardial damage in OSA. This study provides an innovative approach for in vitro studies of OSA cardiovascular morbidity and supports the search for new pharmacological agents and molecular targets to improve diagnosis and treatment of patients. Full article

(This article belongs to the Special Issue Sleep Apnea and Systemic Inflammation)

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Review

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19 pages, 1225 KiB

Open AccessReview

Investigating the Relationship between Obstructive Sleep Apnoea, Inflammation and Cardio-Metabolic Diseases

by Abdulmohsen Alterki, Mohamed Abu-Farha, Eman Al Shawaf, Fahd Al-Mulla and Jehad Abubaker

Int. J. Mol. Sci. 2023, 24(7), 6807; https://doi.org/10.3390/ijms24076807 - 06 Apr 2023

Cited by 6 | Viewed by 2365

Abstract

Obstructive sleep apnoea (OSA) is a prevalent underdiagnosed disorder whose incidence increases with age and weight. Uniquely characterised by frequent breathing interruptions during sleep—known as intermittent hypoxia (IH)—OSA disrupts the circadian rhythm. Patients with OSA have repeated episodes of hypoxia and reoxygenation, leading [...] Read more.

Obstructive sleep apnoea (OSA) is a prevalent underdiagnosed disorder whose incidence increases with age and weight. Uniquely characterised by frequent breathing interruptions during sleep—known as intermittent hypoxia (IH)—OSA disrupts the circadian rhythm. Patients with OSA have repeated episodes of hypoxia and reoxygenation, leading to systemic consequences. OSA consequences range from apparent symptoms like excessive daytime sleepiness, neurocognitive deterioration and decreased quality of life to pathological complications characterised by elevated biomarkers linked to endocrine-metabolic and cardiovascular changes. OSA is a well-recognized risk factor for cardiovascular and cerebrovascular diseases. Furthermore, OSA is linked to other conditions that worsen cardiovascular outcomes, such as obesity. The relationship between OSA and obesity is complex and reciprocal, involving interaction between biological and lifestyle factors. The pathogenesis of both OSA and obesity involve oxidative stress, inflammation and metabolic dysregulation. The current medical practice uses continuous positive airway pressure (CPAP) as the gold standard tool to manage OSA. It has been shown to improve symptoms and cardiac function, reduce cardiovascular risk and normalise biomarkers. Nonetheless, a full understanding of the factors involved in the deleterious effects of OSA and the best methods to eliminate their occurrence are still poorly understood. In this review, we present the factors and evidence linking OSA to increased risk of cardiovascular conditions. Full article

(This article belongs to the Special Issue Sleep Apnea and Systemic Inflammation)

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21 pages, 1240 KiB

Open AccessReview

Sleep-Disordered Breathing and Chronic Respiratory Infections: A Narrative Review in Adult and Pediatric Population

by Paola Faverio, Umberto Zanini, Anna Monzani, Gianfranco Parati, Fabrizio Luppi, Carolina Lombardi and Elisa Perger

Int. J. Mol. Sci. 2023, 24(6), 5504; https://doi.org/10.3390/ijms24065504 - 13 Mar 2023

Cited by 2 | Viewed by 2375

Abstract

Sleep-disordered breathing (SDB) comprises different diseases characterized by abnormal respiratory patterns during sleep including obstructive sleep apnea. SDB prevalence and impact in patients with chronic respiratory infections have been only marginally studied. The purpose of this narrative review is to report the prevalence [...] Read more.

Sleep-disordered breathing (SDB) comprises different diseases characterized by abnormal respiratory patterns during sleep including obstructive sleep apnea. SDB prevalence and impact in patients with chronic respiratory infections have been only marginally studied. The purpose of this narrative review is to report the prevalence and impact of SDB in chronic respiratory infections, including cystic fibrosis (CF), bronchiectasis and mycobacterial infections, and explore the possible pathophysiological mechanisms. Common pathophysiological mechanisms, underlying SDB onset in all chronic respiratory infections, include inflammation, which plays a central role, chronic nocturnal cough and pain, excessive production of mucous plugs, presence of obstructive and/or restrictive ventilatory impairment, upper airways involvement, and comorbidities, such as alteration of nutritional status. SDB may affect about 50% of patients with bronchiectasis. The severity of the disease, e.g., patients colonized with P. aeruginosa and frequent exacerbators, as well as comorbidities, such as chronic obstructive pulmonary disease and primary ciliary dyskinesia, may impact SDB onset. SDB may also frequently complicate the clinical course of both children and adults with CF, impacting the quality of life and disease prognosis, suggesting that their routine assessment should be incorporated into the clinical evaluation of patients from the first stages of the disease regardless of suggestive symptoms, in order to avoid late diagnosis. Finally, although the prevalence of SDB in patients with mycobacterial infections is uncertain, extrapulmonary manifestations, particularly nasopharyngeal locations, and concomitant symptoms, such as body pain and depression, may act as atypical predisposing factors for their development. Full article

(This article belongs to the Special Issue Sleep Apnea and Systemic Inflammation)

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