Nocturnal Intermittent Hypoxia Research Articles

Increased fatigability and impaired skeletal muscle microvascular reactivity in adults with obstructive sleep apnea: a cross-sectional study

BackgroundSympathetic nervous system hyperactivity and chronic intermittent nocturnal hypoxia in individuals with obstructive sleep apnea (OSA) predispose them to microvascular impairment, which may contribute to increased daytime muscle fatigue. This study aimed to assess microvascular reactivity of the skeletal muscle, examine fatigability, and determine the relationship between fatigability and microvascular reactivity in adults with OSA.MethodsTwenty-six participants were allocated into two groups—those with OSA and those without i.e. non-OSA. Each group comprised of 13 individuals who underwent an arterial occlusion test on their non-dominant leg. The percentage change of maximal hyperemic response (MHR) and the time to achieve MHR (tM) of both the total myoglobin/hemoglobin (∆[Hbtot]) and the oxygenated myoglobin/hemoglobin (∆[HbO2]) signals from near-infrared spectroscopy were calculated to examine microvascular reactivity. In addition, a 10-min walk test was performed to assess performance and perceived fatigability.ResultsThe OSA group demonstrated a reduced in ∆[Hbtot]MHR (150.9 ± 16.2% vs. 235.8 ± 72.7%, p = 0.006), ∆[HbO2]MHR (131.4 ± 8% vs. 161.7 ± 10.6%, p = 0.001) and increased ∆[Hbtot]tM (80.5 ± 13.1 s vs. 47.7 ± 9.9 s, p < 0.001), ∆[HbO2]tM (85.2 ± 22.4 s vs. 52.1 ± 5.9 s, p = 0.001) compared to the non-OSA group. In addition, participants in the OSA group experienced greater perceived (6 ± 1 vs. 2.8 ± 0.1, p = 0.001) and performance fatigability (1.1 ± 0.1 vs. 0.9 ± 0.1, p = 0.001) compared to adults in the non-OSA group. Moreover, both performance and perceived fatigability were significantly associated with microvascular reactivity parameters (all p < 0.05).ConclusionMicrovascular dysfunction, as determined by an attenuated post-occlusive reactive hyperemia, is observed in individuals with OSA that may contribute to increased fatigability in these individuals.

Growth Differentiation Factor GDF 15 (“Protein of Senility”) under Conditions of Oxidative Stress and Intermittent Nocturnal Hypoxia in Patients with Sleep Apnea Syndrome

Growth Differentiation Factor GDF 15 (“Protein of Senility”) under Conditions of Oxidative Stress and Intermittent Nocturnal Hypoxia in Patients with Sleep Apnea Syndrome

The latest research progress on the relationship between obstructive sleep apnea–hypopnea syndrome and metabolic syndrome

AbstractObstructive sleep apnea–hypopnea syndrome (OSAHS) is the most common subtype of sleep‐disordered breathing, characterized by symptoms such as snoring, nocturnal sleep disturbances, and excessive daytime sleepiness. OSAHS is defined by recurrent upper airway collapses during sleep, leading to apneas or hypopneas. These episodes result in intermittent nocturnal hypoxia and sleep fragmentation, which provoke sympathetic activation, oxidative stress, and systemic inflammation, ultimately causing chronic damage across multiple bodily systems. OSAHS significantly increases the risk of various cardiovascular and metabolic disorders, including atherosclerosis, hypertension, obesity, insulin resistance, and dyslipidemia. In China, approximately 176 million individuals are estimated to have OSAHS, with about 60 million experiencing moderate to severe forms of the condition. This paper reviews the epidemiological characteristics of OSAHS, the evolution of diagnostic criteria, and the association between OSAHS and metabolic syndrome (MetS), emphasizing the high prevalence of MetS among OSAHS patients. Through cross‐sectional analysis, cohort studies, and interventional studies, the complex interactions between OSAHS and MetS are examined, proposing therapeutic strategies to improve these metabolic anomalies, including continuous positive airway pressure therapy and weight management.

Ultrasonographic changes and impact factors of diaphragmatic function in patients with obstructive sleep apnea-hypopnea syndrome.

Diaphragmatic impairment has been reported in obstructive sleep apnea-hypopnea syndrome (OSAHS) patients. However, the risk factors of diaphragmatic dysfunction are unclear. This study was conducted to evaluate the diaphragmatic function and to investigate impact factors of ultrasonographic changes of the diaphragm in OSAHS patients. This cross-sectional study recruited 150 snoring patients. All patients were divided into the control group (AHI < 5/h, n = 20), the mild-to-moderate OSAHS group (5/h ≤ AHI ≤ 30/h, n = 61), and the severe OSAHS group (AHI > 30/h, n = 69). Diaphragmatic thickness at function residual capacity (TFRC) and total lung capacity (TTLC) were measured by two-dimensional ultrasound, and the diaphragmatic excursion during tidal and deep breath was measured by M-mode ultrasound. The diaphragmatic thickening fraction (TF) was calculated. Spearman analysis and multiple linear stepwise regression analysis were conducted to analyze the impact factors of diaphragmatic function. TFRC in the control group, mild-to-moderate OSAHS group, and severe OSAHS group was 1.23 (1.10, 1.39) mm, 1.60 (1.43, 1.85) mm, and 1.90 (1.70, 2.25) mm; TTLC was 2.75 (2.53, 2.93) mm, 3.25 (2.90, 3.55) mm, and 3.60 (3.33, 3.90) mm, and TF was 119.23% (102.94, 155.97), 96.55% (74.34, 119.11), and 85.29% (60.68,101.22). There were across-group significant differences in TFRC, TTLC, and TF (P < 0.05). The oxygen desaturation index was the influencing factor of TFRC, TTLC, and TF (P < 0.05). The diaphragm is thickened and diaphragmatic contractility is decreased in OSAHS patients. Nocturnal intermittent hypoxia is a risk factor for diaphragmatic hypertrophy and impaired diaphragmatic contractility.

Changes the level of differentiating growth factor - GDF 15 in patients with sleep apnea syndrome after aPAP-therapy: pilot study

Comparative assessment of the level of differentiating growth factor 15 (GDF 15 ) against the background of a 6-month course of respiratory support in the mode of automatic positive pressure in the airways therapy (aPAP therapy) in patients with obstructive sleep apnea syndrome (OSA). 59 men participated in the study, the average age was 51.9±2.4 years. The main group (MG1) consisted of 30 patients with a verified diagnosis of moderate OSA. 29 men of comparable age and body weight made up the control group (CG) without an objectively confirmed diagnosis of OSA. After the stage of introduction into the study, the type of respiratory support with individual pressure settings was selected for patients with MG1. After 6 months of aPAP therapy with high compliance (at least 85%), the same patients who made up MG2 after treatment underwent repeated polysomnography (PSG) and the GDF 15 content was evaluated. Methods: questionnaire, examination, polysomnography, enzyme immunoassay of blood serum to determine the content of GDF 15. A 6-month course of aPAP therapy with a high degree of compliance significantly improved the sleep structure and breathing pattern: the representation of NREM 3 increased from 79.2±15.6 to 102.6±21.6 minutes and the REM phase from 56.9± 13.6 to 115.6±26.8. Episodes of apnea were eliminated - apnea-hypopnea index decreased from 21.1 [17.3; 39.1] to 2.5 [1.8; 4.6] and the average values of SaO2 increased from 85.9% to 91.5%. At the same time, a statistically significant excess of GDF 15 was revealed in MG1 - 20.4 [14.16; 31.71] and MG2 - 17.2 [13.63; 24.44]) in comparison with CG - 13.65 [10.7; 17.09]. Despite the lack of statistical significance, a change in the level of GDF 15 was revealed in the form of a decrease in its concentration after a 6-month course of aPAP therapy. A 6-month course of aPAP therapy made it possible to eliminate intermittent nocturnal hypoxia and improve sleep structure in patients with OSA, as well as reduce the content of GDF 15 protein in blood serum in patients with OSA. However, the tendency to decrease the content of this protein, despite the lack of statistical reliability, confirms the effectiveness of OSA therapy and the possibility of preventing early and pathological aging from the standpoint of somnology and molecular biogerontology.

Nocturnal Intermittent Hypoxia and the Risk of Cardiovascular Disease among Japanese Populations: The Circulatory Risk in Communities Study (CIRCS).

Information is limited about the influence of obstructive sleep apnea (OSA) on developing cardiovascular disease (CVD) among Asian community-dwelling populations. We examined the association between nocturnal intermittent hypoxia as a surrogate marker of OSA and the risk of CVD in a Japanese community-based cohort study. We used baseline surveys from 2000 to 2008 to study the cohort data of 5,313 residents from three Japanese communities who were between the ages of 40 and 74 years and initially free from ischemic heart disease and stroke. We assessed the number of 3% oxygen desaturation index (ODI) as the indicator of nocturnal intermittent hypoxia. We divided individuals into two groups depending on 3% ODI (3% ODI ≥ 5 or 3% ODI ＜5). Cox proportional hazards regression models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for CVD according to 3% ODI. Age, sex, body mass index, alcohol, and smoking were adjusted in the multivariable models. During 12.8 years of the median follow-up with 66,796 person-years, 185 cases with CVD (115 stroke and 70 coronary heart disease [CHD]) were recorded. The multivariable HRs (95% CIs) were 1.49 (1.09-2.03), 2.13 (1.08-4.22), and 1.93 (1.16-3.19) for the 3% ODI ≥ 5 group versus the 3% ODI ＜5 group of developing CVD, lacunar infarction, and CHD, respectively. Nocturnal intermittent hypoxia may increase the risk of developing lacunar infarction and CHD among community-dwelling Japanese populations. However, we could not find a significant risk of developing total stroke or stroke subtypes such as intraparenchymal hemorrhage, subarachnoid hemorrhage, and total ischemic stroke.

Obstructive sleep apnea syndrome: nocturnal intermittent hypoxia and telomerase complex activity

Obstructive sleep apnea syndrome (OSAS) is a common pathology of the respiratory system characterized by upper airway blockage during sleep. The blockage is caused by intermittent throat collapse and thereby no lung ventilation with preserved respiratory efforts. Earlier we demonstrated that telomeres at the end of chromosomes shorten during intermittent nocturnal hypoxia and sleep fragmentation in OSA patients; the elimination of OSA triggers contributed to an increase in relative telomere length (RTL). The search for the relationship between telomeres and the telomerase complex activity with the sleep stages, as well as indicators of blood oxygen saturation in OSA, seems relevant.Aim. To evaluate the activity of the telomerase complex main components and to determine its relationship with the sleep phases and the level of desaturation in patients with OSA.Methods. The main group included 32 men (age 51.2 ± 3.1 years) with complaints of snoring, respiratory arrest during sleep, and increased daytime sleep. The control group consisted of 26 matched volunteers without clinical manifestations of OSA. Patients of both groups did not have any exacerbations of their chronic conditions at baseline. The study included questionnaires, polysomnography monitoring, analysis of the RLT by PCR, ELISA to determine activity of the telomerase complex components, and statistical analysis.Results. Differences were revealed in the functioning of telomeres and the TERT, TEP1. A positive relationship between the oxygen blood saturation, telomere length and TER1 activity was found in OSA patients.Conclusion. We have identified the decrease in RTL and the telomerase complex activity and proved their positive relationship with the oxygen saturation during intermittent nocturnal hypoxia in OSA patients.

Cerebral microangiopathy in men with obstructive sleep apnea syndrome

To determine factors associated with the development of small vessel disease (SVD) in patients with obstructive sleep apnea syndrome (OSA). One hundred and fifty-two patients with risk factors for the development of cerebrovascular diseases were examined. Based on the results of polysomnography, patients were divided into groups with- (n=84) and without (n=68) OSA. The groups were matched by age, prevalence of arterial hypertension and diabetes mellitus. SVD was diagnosed using brain MRI. Laboratory tests included an assessment of parameters of lipid metabolism, glucose metabolism, concentration of C-reactive protein (CRP), levels of homocysteine and creatinine with the calculation of glomerular filtration rate (GFR). Patients with OSA, compared with those without OSA, were characterized by a statistically significant number of gliosis foci, with their large sizes, more frequent changes on the Fazekas scales and the Hassan scale. The most severe degree of damage according to the Hassan scale in patients with OSA was detected more often (55 (66%) and 27 (39%) OR=2.89, 95% CI 1.47-5.67, p=0.002). More pronounced atrophic changes in the brain, an increase in the size of the III ventricle and the index of the anterior horns, significantly lower GFR and higher levels of CRP were noted in the OSA group. Patients with OSA and duration of nocturnal hypoxia for more than 2 minutes were more likely to have hyperintensity of subcortical regions. In patients with OSAS, pronounced manifestations of SMD were associated with a significantly higher level of morning systolic blood pressure (MAP): 140 [120; 150] vs. 127 [120; 130] p=0.029; increased levels of blood homocysteine: 14 [11; 17.8] vs. 13 [9.7; 12.5] p=0.049; a decrease in GFR: 79 [71; 87.3] vs. 89.8 [80.3; 94] p=0.002, respectively. OSA and intermittent nocturnal hypoxia are independent risk factors for SMD. A more severe micro-focal vascular lesion in OSA is associated with a decrease in renal filtration function, an increase in morning blood pressure and an elevation in homocysteine level.

Sleep pattern changes in patients with lung cancer

Background: There are multiple connections between sleep and lung cancer. Both of them impacting each other lung cancer can make it difficult to sleep well due to symptoms and treatment side effects( 20-70% of cancer patients suffer of insomnia) .Also there is possible relationship between lung cancer and nocturnal intermittent hypoxia, apnea and daytime sleepiness, progression of lung cancer considered as risk factor of obstructive sleep apnea severity. Aim of the work: to evaluate sleep pattern changes in patients with lung cancer. Patients and methods: 26 patients with non small cell lung cancer were interviewed for assessment of histopathological subtypes and stages according to TNM classification and treated at Department of Clinical Oncology and Nuclear Medicine (chemotherapy, radiotherapy, targeted therapy and surgical treatment were scheduled), they underwent to sleep questionnaire and Epworth Sleepiness Score (ESS).overnight full polysomnography was done.

Independent Association Between Oxygen Desaturation Index and Cardiovascular Disease in Non-Sleepy Sleep-Disordered Breathing Subtype: A Chinese Community-Based Study.

PurposeNon-sleepy sleep-disordered breathing (SDB) is increasingly recognized as an important clinical subtype. The association between non-sleepy SDB and cardiovascular disease (CVD) is not well understood. Our objectives were to investigate the relationship between non-sleepy SDB and CVD and determine which nocturnal hypoxia parameter most strongly reflects this association in a large community population.Patients and MethodsCross-sectional data from 3626 randomly-selected Chinese community-dwelling participants who underwent overnight type IV sleep monitoring were analyzed. Parameters of nocturnal hypoxemia were extracted from sleep monitoring devices, including mean nocturnal oxygen saturation, lowest oxygen saturation, oxygen desaturation index (ODI), and time with oxygen saturation <90%. An ODI ≥7.0 events/h was considered to signify SDB. An Epworth Sleepiness Scale score of 10 or less indicated no sleepiness.ResultsThe SDB rate was 30.7% (1114/3626), of which 96.5% (1075/1114) were considered the non-sleepy SDB subtype. ODI, typical nocturnal intermittent hypoxia indicator for SDB, was independently related to CVD, regardless of whether excessive daytime sleepiness was present. After adjusting for confounders, ODI most strongly reflected the association between non-sleepy SDB and CVD (OR:1.023; 95% CI:1.003–1.043). We observed a nonlinear association between ODI and the prevalence of CVD, where the likelihood of CVD increased with ODI≥10 events/h and a markedly increasing trend was observed with ODI ≥20 events/h (reference ODI = 7.0 events/h). Metabolic parameters, Pittsburgh Sleep Quality Index, and inflammatory marker did not mediate the association between ODI and CVD in the non-sleepy SDB subtype.ConclusionIn the Chinese community-dwelling population, non-sleepy SDB was highly prevalent. ODI, an easily extracted indicator from a type IV sleep monitor, most strongly reflected the association between non-sleepy SDB and CVD.

Obstructive sleep apnea and amyloid-β42 in adolescents: The results of a pilot study

Background. Obstructive sleep apnea (OSA) is a chronic condition characterized by repetitive collapse of the upper airway during sleep leading to intermittent hypoxia, excessive arousals and disrupt of sleep homeostasis. OSA is associated with obesity as well as pathological dynamics of cerebral beta-amyloid and dementia.The aim. Comparative assessment of the plasma beta-amyloid 42 levels in adolescents, depending on the presence or absence of OSA and obesity.Materials and methods. Seventy-four obese and non-obese male adolescents were included in the study. All participants underwent polysomnography to verify OSA and measure sleep parameters, and venipuncture for the assessment of betaamyloid 42 by enzyme-linked immunosorbent assay (ELISA).Results. After polysomnography all adolescents have been divided into four study groups: OSA obese (group 1; n = 28); non-OSA obese (group 2; n = 20); OSA non-obese (group 3; n = 11), and non-OSA non-obese (group 4 – control; n = 15). OSA obese adolescents had significant elevations in beta-amyloid 42 plasma levels compared with participants from three other groups (р = 0.007, p = 0.047 and p = 0.0002, correspondingly). Compared to both OSA non-obese adolescents and the control group, non-OSA obese patients had similar beta-amyloid 42 blood concentrations (p = 0.167 and p = 0.155, correspondingly). However, patients from the group 3 showed significantly higher beta-amyloid 42 plasma levels than controls (p = 0.004).Conclusions. Thus, OSA, accompanied by intermittent nocturnal hypoxia, and particularly OSA and obesity comorbidity, in adolescents is associated with increased beta-amyloid 42 circulating concentrations, which has a major role in pathogenesis of dementia. Beta-amyloid 42 plasma level may be recommended for use as early biomarker of cognitive impairment and neurodegenerative diseases, but future researches are needed.

Effects of Obstructive Sleep Apnea-Hypopnea Syndrome and Cognitive Function in Ischemic Stroke Based on Linear Regression Equation.

The objective of this research is to study the effect of obstructive sleep apnea-hypopnea syndrome on cognitive function of stroke. Based on linear regression equation and Montreal Cognitive Assessment Scale, the degree of cognitive impairment in OSAHS patients was evaluated and the influencing factors of OSAHS-induced cognitive impairment and the correlation between the degree of OSAHS and cognitive impairment were explored. The results are as follows: about 68% of OSAHS patients have cognitive dysfunction, and the incidence of cognitive dysfunction is positively correlated with OSAHS; cognitive impairment of OSAHS patients was associated with age, obesity, years of schooling, and intermittent nocturnal hypoxia or hypoventilation; the severity of cognitive dysfunction of OSAHS patients was positively correlated with age and obesity but negatively correlated with education level; Logistic regression analysis results showed that there were three factors that were finally entered into the regression equation, namely, LSaO2, BMI, and AHI, and the Logistic regression equation obtained was as follows: LogistP = −0.109X1 + 0.785X2 + 1.228X3. This study helps clinical workers to detect and intervene the impaired cognitive ability of patients with OSAHS early, so as to reduce the incidence and mortality of related complications and improve the quality of life of patients.

Obstructive sleep apnea syndrome: association of serum melatonin, increased daytime sleepiness, and intermitting night hypoxemia

The relevance of studies related to the features of respiratory disorders during sleep is undeniable due to the steady growth of the worldwide prevalence of apnea syndrome, which leads to a decrease in quality of life, the risk of early cardiovascular diseases together with cerebrovascular, endocrine, and pulmonary disorders.The aim of this study was to determine the relationship between the morning serum melatonin, blood oxygen saturation (SрO2), and increased daytime sleepiness in patients with SOAS, as well as to assess changes in the production of endogenous melatonin after eliminating clinical manifestations of nocturnal hypoxemia, through a 3-month course of non-invasive continuous positive airway pressure (CPAP) therapy. The study enrolled 30 male patients who came to the Federal State Public Scientific Institution “Scientific Centre of Family Health and Human Reproduction Problems” because of snoring, sleep apnea, and increased daytime sleepiness.Methods. Polysomnography, questionnaire, HPLC-MS/MS analysis of serum melatonin levels, CPAP-therapy for the respiratory support at home for 3 months, monitoring of the sleep scores, serum melatonin, and daytime sleepiness after the treatment.Results. A comparative assessment of the sleep scores before and after the respiratory support for 3 months revealed a significant improvement in sleep structure, elimination of the apnea episodes, and restoration of blood SрO2 after the therapy. Analysis of the serum melatonin vales confirmed a statistically significant increase of melatonin level against baseline in patients with SOAS after the treatment. A correlation analysis showed a relationship between the melatonin level, daytime sleepiness, and blood SрO2.Conclusion. The results of this study and the data of other researchers demonstrate that the elimination of intermittent nocturnal hypoxia in patients with SOAS allows reducing the morning serum melatonin level, thereby reducing the daytime sleepiness and subsequently improving the quality of life.

Angiotensin II receptor blocker irbesartan attenuates sleep apnea-induced cardiac apoptosis and enhances cardiac survival and Sirtuin 1 upregulation.

The purpose of this study was to investigate whether or not angiotensin II type 1 receptor blocker irbesartan (ARB) with a partial agonist of PPAR-γ could protect against chronic nocturnal intermittent hypoxia (CIH)-induced cardiac Fas/FasL-mediated to mitochondria-mediated apoptosis. Sprague-Dawley rats were in a normoxic control group (CON-G), or rats werein a chronic nocturnal intermittent hypoxia group (HP-G, from 3 to 7% oxygen versus 21% oxygen per forty seconds cycle, nocturnally 8h per day for 1month), or rats were in a chronic nocturnal intermittent hypoxia group pretreated withARB (50mg/kg/day, S.C.) (ARB-HP-G). Echocardiography, H&E staining, TUNEL staining, and Western blotting were measured inthe left ventricle. Hypoxia-induced SIRT1 degradation, Fas receptors, FADD, active caspase-8 and caspase-3 (Fas/FasL apoptotic pathway) and Bax, tBid, active caspase-9 and -3 (mitochondrial apoptotic pathway) and TUNEL-positive apoptosis were reduced in ARB-HP-G when compared with HP-G. IGF-I, IGF1 receptor, p-PI3k, p-Akt, Bcl2, and Bcl-XL (IGF1/PI3K/AKT pro-survival pathway) were increased in ARB-HP-G compared to HP-G. Our findings suggest that the ARB may prevent cardiac Fas/FasL to mitochondrial apoptotic pathways and enhance cardiac IGF1/PI3K/AKT pro-survival pathway in the sleep apnea model associated with JNK de-activation and SIRT1 upregulation. ARB prevents chronic sleep apnea-enhanced cardiac apoptosis via enhancing survival pathways.

Circulating Malondialdehyde Concentrations in Obstructive Sleep Apnea (OSA): A Systematic Review and Meta-Analysis with Meta-Regression.

Oxidative stress induced by nocturnal intermittent hypoxia plays a significant pathophysiological role in obstructive sleep apnea (OSA). Malondialdehyde (MDA), one of the most commonly investigated markers of lipid peroxidation, might assist with the monitoring of oxidative balance in OSA. We conducted a systematic review and meta-analysis to evaluate the differences in circulating MDA concentrations between patients with OSA and non-OSA controls. A systematic search was conducted in the electronic databases Pubmed, Web of Science, Scopus and Google Scholar from inception to December 2020 by using the following terms: “malondialdehyde” or “MDA”; and “Obstructive Sleep Apnea Syndrome”, “OSAS” or “OSA”. We identified 26 studies in 1223 OSA patients and 716 controls. The pooled MDA concentrations were significantly higher in patients with OSA (standardized mean difference (SMD) 1.43 μmol/L, 95% confidence interval (CI) 1.03 to 1.83 μmol/L, p < 0.001). There was extreme heterogeneity between the studies (I2 = 92.3%, p < 0.001). In meta-regression analysis, the SMD was significantly associated with age, the assay type used and publication year. In our meta-analysis, MDA concentrations were significantly higher in OSA patients than in controls. This finding suggests that MDA, which is a marker of lipid peroxidation, is involved in the pathogenesis of OSA and provides insights for future studies investigating its potential clinical use.

158P Obstructive sleep apnea and breast cancer incidence: A systematic review and meta-analysis

Obstructive sleep apnea (OSA) is a prevalent form of sleep-disordered breathing. Emerging evidence from animal models suggests that intermittent nocturnal hypoxia in OSA may induce carcinogenesis. However, epidemiological studies have reported conflicting findings on this relationship. We conducted this systematic review and meta-analysis to evaluate the association between OSA and breast cancer - the most common cancer in women worldwide.

Association of Obstructive Sleep Apnea with Nocturnal Hypoxemia in Metabolic-Associated Fatty Liver Disease Patients: A Cross-sectional Analysis of Record-based Data.

Rationale:Obstructive sleep apnea (OSA) is often seen among obese individuals and the obesity has a linear association with MAFLD. The contribution of chronic intermittent nocturnal hypoxia of OSA and association of MAFLD with OSA is an unmet need. The present study aimed to determine the etiology, impact and association of OSA severity and nocturnal hypoxemia among patients ofChronic liver disease (CLD).Methods:In this study, analysis of the medical records and clinical details of the patients of CLD who had undergone polysomnography were analyzed after appropriate inclusion in study as per inclusion and exclusion criteria. After assessing the eligibility criteria, a total of 78 patients were included in the final analysis. Nocturnal hypoxemia was gauged from the baseline oxygen saturation record of study. Presence and severity of OSA were graded as per American Academy of Sleep Medicine (AASM) criteria. The primary objective of the study was to determine the association between OSA severity and nocturnal hypoxemia to the presence of Non-alcoholic Fatty Liver Disease (NAFLD). Secondary objectives were to assess the association of OSA severity and extent of nocturnal hypoxemia to the BMI and to determine the proportions of NAFLD subjects with OSA.Results:A total of 78 patients were screened, of which only 11 (14.1%) were female. Out of these, 56 (71.8%) were classified to MAFLD group while 22 (28.2%) were to the non-MAFLD group. The patients in MAFLD group with mean age of 56.02 years were older as compared to non-MAFLD with mean age of 51.05 years but that was not statistically different. Patients were categorized into MAFLD (n = 56) and non-MAFLD, representing other etiologies of CLD (n = 22; ethanol, chronic Hepatitis B virus (HBV), chronic Hepatitis C virus (HCV), cryptogenic, Non-cirrhosis portal fibrosis (NCPF), Primary sclerosing cholangitis (PSC), Autoimmune hepatitis (AIH), sarcoidosis, Wilson's disease). The mean BMI was significantly higher in MAFLD in comparison to non-MAFLD (34.51 ± 8.79 vs. 25.47 ± 5.75; P = 0.000) and also the median AHI of MAFLD group was significantly higher than the non-MAFLD 4.95 {(1.85, 25.47) vs. 0.85 (0.30, 2.72) (P value < 0.000)} [Table 1]. Among the desaturation indices, the number of desaturations >3% {median of 122.50 (75.00, 241.25) vs. 63.00 (13.75, 158.00), P value 0.009} and average desaturation {mean of (5.04 ± 2.16) vs. (3.78 ± 1.226)%, P value 0.002} were significantly higher in MAFLD versus non-MAFLD group [Table 2]. The AHI and all desaturation parameters, although not statistically significant, were worst in Child B [Table 3].Conclusion:MAFLD patients have higher prevalence and greater severity of OSA and worse nocturnal desaturation parameters as compared to non-MAFLD patients. OSA is independent of obesity among patients of CLD, but prevalent among NAFLD group. Further prospective studies are needed among MAFLD and OSA patients to elucidate the mechanism linking pathophysiology of OSA-MAFLD and guide therapy.

Association Of Nocturnal Intermittent Hypoxia With Heat Shock Protein 70 In Patients With Obstructive Sleep Apnea: A Pilot Study

Introduction — Nocturnal intermittent hypoxia in obstructive sleep apnea (OSA) causes cellular stress and consequent change in inducible heat shock protein 70 (HSP70) level. Thus, the objective of this study was to determine the relationship among nocturnal hypoxia and the serum HSP70 level in patients with severe OSA. Material and Methods — The study involved 34 patients with a clinical diagnosis of moderate to severe OSA (24 men and 10 women). Patients without OSA (10 men and 5 women) were included as a control group. The groups were similar in age. The polysomnographic monitoring was carried by standart methodology. Blood sampling for determining the HSP70 level was carried out between 8:00 and 9:00 am after polysomnographic monitoring. Results — The results of this study demonstrated a high apnea/hypopnea index (AHI), which determined the OSA severity and decreased the blood oxygen saturation (SaO2) (p&lt;0.05). Sleep fragmentation in OSA patients confirmed an increase in respiratory arousal index (ArI). The HSP70 level significantly increased in OSA patients compared with the control group. Correlation analysis showed a positive relationship between HSP70 and AHI (R=0.5) in patients with OSAS, as well as a negative relationship between HSP70 and SaO2 (R=-0.3). Conclusion — Our results demonstrated a high level of HSP70 in patients with severe OSA syndrome vs. those without it. In OSA patients, a direct correlation was found between the HSP70 level and AHI, as well as an inverse correlation between the AHI level and SaO2. These findings suggested an association between the level of inducible HSP70 and nocturnal hypoxia in OSA patients.

Intrahepatic Expression of Fatty Acid Translocase CD36 Is Increased in Obstructive Sleep Apnea.

Nocturnal intermittent hypoxia (IH) featuring obstructive sleep apnea (OSA) dysregulates hepatic lipid metabolism and might contribute to the development of non-alcoholic fatty liver disease (NAFLD) observed in OSA patients. However, further research is required to better understanding the molecular mechanisms underlying IH-induced hepatic lipid accumulation. Therefore, the aim of the present study was to determine the effects of OSA on hepatic CD36 expression and the impact of IH by using a mouse model of OSA. Histological analysis, lipid content and CD36 expression were assessed in livers from subjects who underwent liver biopsy and polygraphic study during sleep, and in livers from mice submitted to chronic IH mimicking OSA. Among those who presented OSA features, NAFLD were significantly more frequent than in control subjects with normal respiratory function (77.8 vs. 36.4%, respectively), and showed more severe liver disease. Interestingly, CD36 expression was significantly overexpressed within the liver of OSA patients with respect to controls, and a significant positive correlation was observed between hepatic levels of CD36 and the values of two well-known respiratory parameters that characterized OSA: apnea/hypopnea index (AHI) and oxygen desaturation index (ODI). Moreover, hepatic lipid accumulation as well as induction of hepatic lipogenic genes, and CD36 mRNA and protein expression were significantly higher in livers from mice exposed to IH conditions for 8 weeks than in their corresponding littermates. This study provides novel evidence that IH featuring OSA could contribute to NAFLD setup partly by upregulating hepatic CD36 expression.

Patients with obstructive sleep apnea present with chronic upregulation of serum HIF-1α protein

Obstructive sleep apnea (OSA) is a chronic condition that is characterized by recurrent pauses in breathing during sleep causing intermittent hypoxia. The main factor responsible for oxygen metabolism homeostasis is hypoxia-inducible factor 1 (HIF-1), comprised of 2 subunits: α (oxygen sensitive) and β. The aim of the study was to investigate the HIF-1α serum protein level and mRNA HIF-1α expression in patients with OSA and a healthy control group and determine their evening-morning variation and association with polysomnography parameters. Eighty-four individuals were enrolled in the study. All patients underwent polysomnography examination and based on the results were divided into 2 groups: OSA group (n = 60) and control group (n = 24). Peripheral blood was collected in the evening before and in the morning after the polysomnography. HIF-1α expression was evaluated on protein in blood serum and mRNA level in peripheral blood leukocytes. HIF-1α serum protein concentration was higher in patients with OSA compared with control patients in both the evening (1,490.1 vs. 727.0 pg/mL; P < .001) and the morning (1,368.9 vs. 702.1 pg/mL; P < .001) samples. There was no difference between evening and morning HIF-1α serum protein level in either group. No differences were observed in HIF-1α mRNA expression between the OSA and control group. Additionally, evening and morning HIF-1α serum protein level correlated with number of desaturations during sleep (r = .384, P < .001 and r = .433, P < .001, respectively). Observed differences in HIF-1α serum protein level between the OSA and the control groups without difference between evening and morning measurements suggest chronic increase in this protein concentration by intermittent nocturnal hypoxia in OSA.