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Interdisciplinary Weight Loss and Lifestyle Intervention for Obstructive Sleep Apnoea in Adults: Rationale, Design and Methodology of the INTERAPNEA Study.
Carneiro-Barrera, A, Amaro-Gahete, FJ, Díaz-Román, A, Guillén-Riquelme, A, Jurado-Fasoli, L, Sáez-Roca, G, Martín-Carrasco, C, Ruiz, JR, Buela-Casal, G
Nutrients. 2019;(9)
Abstract
Obesity is a major risk factor for obstructive sleep apnoea (OSA), the most common sleep-disordered breathing related to neurocognitive and metabolic syndromes, type II diabetes, and cardiovascular diseases. Although strongly recommended for this condition, there are no studies on the effectiveness of an interdisciplinary weight loss and lifestyle intervention including nutrition, exercise, sleep hygiene, and smoking and alcohol cessation. INTERAPNEA is a randomised controlled trial with a two-arm parallel design aimed at determining the effects of an interdisciplinary tailored weight loss and lifestyle intervention on OSA outcomes. The study will include 84 males aged 18-65 with a body mass index of ≥25 kg/m2 and severe to moderate OSA randomly assigned to usual care (i.e., continuous positive airway pressure), or interdisciplinary weight loss and lifestyle intervention combined with usual care. Outcomes will be measured at baseline, intervention end-point, and six-month post-intervention, including apnoea-hypopnoea index (primary outcome), other neurophysical and cardiorespiratory polysomnographic outcomes, sleep quality, daily functioning and mood, body weight and composition, physical fitness, blood biomarkers, health-related quality of life, and cost-effectiveness. INTERAPNEA may serve to establish a cost-effective treatment not only for the improvement of OSA and its vast and severe comorbidities, but also for a potential remission of this condition.
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Relationships between cardiometabolic disorders and obstructive sleep apnea: Implications for cardiovascular disease risk.
Zhao, X, Li, X, Xu, H, Qian, Y, Fang, F, Yi, H, Guan, J, Yin, SK
Journal of clinical hypertension (Greenwich, Conn.). 2019;(2):280-290
Abstract
Previous studies have reported the effects of obstructive sleep apnea (OSA) and cardiometabolic disorders on cardiovascular disease (CVD), but associations between cardiometabolic biomarkers and two cardinal features of OSA (chronic intermittent hypoxia and sleep fragmentation) and their interactions on CVD in OSA populations remain unclear. A total of 1727 subjects were included in this observational study. Data on overnight polysomnography parameters, biochemical biomarkers, and anthropometric measurements were collected. Metabolic syndrome (MS), including blood pressure, waist circumference (WC), fasting glucose, triglycerides (TG), and high-density lipoprotein cholesterol (HDL-C), was diagnosed based on modified criteria of the Adult Treatment Panel III. WC, mean arterial pressure, TG and low-density lipoprotein cholesterol (LDL-C) were independently associated with apnea-hypopnea index (AHI) after adjustment for confounding factors (β = 0.578, P = 0.000; β = 0.157, P = 0.001; β = 1.003, P = 0.019; and β = 4.067, P = 0.0005, respectively). Furthermore, the interaction analysis revealed joint effects between hypertension, obesity, hyperglycemia, and LDL-C dyslipidemia and AHI on CVD. The relative excess risks of CVD due to the interactions with OSA were 2.06, 1.02, 0.48, and 1.42, respectively (all P < 0.05). In contrast, we found no independent effect of the microarousal index (MAI) on CVD. However, LDL-C level and some MS components (WC, TG) were associated with MAI. Our findings indicate that hypoxemia and cardiometabolic disorders in OSA may potentiate their unfavorable effects on CVD. Sleep fragmentation may indirectly predispose patients with OSA to an increased risk of CVD. Thus, cardiometabolic disorders and OSA synergistically influence cardiometabolic risk patterns.
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Multiethnic Meta-Analysis Identifies RAI1 as a Possible Obstructive Sleep Apnea-related Quantitative Trait Locus in Men.
Chen, H, Cade, BE, Gleason, KJ, Bjonnes, AC, Stilp, AM, Sofer, T, Conomos, MP, Ancoli-Israel, S, Arens, R, Azarbarzin, A, et al
American journal of respiratory cell and molecular biology. 2018;(3):391-401
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Abstract
Obstructive sleep apnea (OSA) is a common heritable disorder displaying marked sexual dimorphism in disease prevalence and progression. Previous genetic association studies have identified a few genetic loci associated with OSA and related quantitative traits, but they have only focused on single ethnic groups, and a large proportion of the heritability remains unexplained. The apnea-hypopnea index (AHI) is a commonly used quantitative measure characterizing OSA severity. Because OSA differs by sex, and the pathophysiology of obstructive events differ in rapid eye movement (REM) and non-REM (NREM) sleep, we hypothesized that additional genetic association signals would be identified by analyzing the NREM/REM-specific AHI and by conducting sex-specific analyses in multiethnic samples. We performed genome-wide association tests for up to 19,733 participants of African, Asian, European, and Hispanic/Latino American ancestry in 7 studies. We identified rs12936587 on chromosome 17 as a possible quantitative trait locus for NREM AHI in men (N = 6,737; P = 1.7 × 10-8) but not in women (P = 0.77). The association with NREM AHI was replicated in a physiological research study (N = 67; P = 0.047). This locus overlapping the RAI1 gene and encompassing genes PEMT1, SREBF1, and RASD1 was previously reported to be associated with coronary artery disease, lipid metabolism, and implicated in Potocki-Lupski syndrome and Smith-Magenis syndrome, which are characterized by abnormal sleep phenotypes. We also identified gene-by-sex interactions in suggestive association regions, suggesting that genetic variants for AHI appear to vary by sex, consistent with the clinical observations of strong sexual dimorphism.
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Obstructive sleep apnea and the metabolic syndrome: The road to clinically-meaningful phenotyping, improved prognosis, and personalized treatment.
Gaines, J, Vgontzas, AN, Fernandez-Mendoza, J, Bixler, EO
Sleep medicine reviews. 2018;:211-219
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Abstract
Obstructive sleep apnea (OSA) is an increasingly prevalent sleep disorder characterized by upper airway obstruction during sleep, resulting in breathing pauses, intermittent hypoxia, and fragmented sleep. In parallel, the constellation of adverse health outcomes associated with prolonged obesity, such as insulin resistance, elevated blood pressure, triglycerides, and reduced high-density lipoprotein cholesterol - termed metabolic syndrome -raises the risk of cardiovascular morbidity and mortality, type 2 diabetes, and all-cause mortality. Affecting 35-40% of U.S. adults, risk factors for metabolic syndrome, including obesity, middle age, sedentary behavior, and genetics, share considerable overlap with those for OSA. Thus, it has been difficult to disentangle cause, effect, and whether certain treatments, such as CPAP, can improve these outcomes. In this paper, we provide an update to our 2005 review which explored the association between OSA and metabolic syndrome, highlighting visceral obesity as the common etiological factor of both conditions. This update includes (a) recent data on physiological and biochemical mechanisms, (b) new data in nonobese men and women as well as children and adolescents, (c) insight from the latest treatment studies, (d) the role of aging in understanding clinically-meaningful phenotypes of the disorder, and (e) the potential diagnostic/prognostic utility of biomarkers in identifying OSA patients with the strongest cardiometabolic risk.
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Concurrent presence of inflammation and obstructive sleep apnea exacerbates the risk of metabolic syndrome: A KoGES 6-year follow-up study.
Kim, J, Yoon, DW, Lee, SK, Lee, S, Choi, KM, Robert, TJ, Shin, C
Medicine. 2017;(7):e4488
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Obstructive sleep apnea (OSA) leads to multiple end-organ morbidities that are mediated by the cumulative burden of oxidative stress and inflammation. Both OSA and inflammation play key roles in increased risk of cardiovascular disease (CVD). Thus, we hypothesized that the combination of inflammation and OSA could accelerate the development of metabolic syndrome (MetS) in a large cohort study.A total of 1835 participants were randomly selected from the ongoing Korean Genome and Epidemiology Study for the years between 2007 and 2015. Overnight polysomnography was performed on each participant. Blood was drawn for biochemical analyses. Participants with high or low inflammation were divided by high-sensitivity C-reactive protein (hsCRP). MetS was defined using the criteria of the modified National Cholesterol Education Program, Adult Treatment Panel III.The prevalence of MetS was higher among the subjects with OSA and high hsCRP levels than among the other corresponding groups. The incidence of MetS among the 4 groups stratified by OSA and inflammation status at the 6-year follow-up was 11.8%, 19.9%, 25.8%, and 36.0% (HsCRP[-]/OSA[-] vs HsCRP[+]/OSA[-] vs HsCRP[-]/OSA[+] vs HsCRP[+]/OSA[+], P < 0.01). After adjusting for age, sex, smoking, alcohol status, BMI, and change in BMI (ΔBMI) in a multiple logistic regression, the subjects with OSA and high hsCRP levels at follow-up had a 2.22-fold risk of developing MetS, as compared with those with no-OSA and low hsCRP levels (P < 0.01).MetS is more prevalent in the concurrent presence of inflammation and OSA. The combination of these conditions is associated with higher risk of MetS. Additional research is needed to help further define the significance of the combined effect of OSA and subclinical inflammation on the development of MetS in the context of reduction of CVD risk.
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Obstructive sleep apnea and weight loss treatment outcome among adults with metabolic syndrome.
Whited, MC, Olendzki, E, Ma, Y, Waring, ME, Schneider, KL, Appelhans, BM, Busch, AM, Chesebro, J, Pagoto, SL
Health psychology : official journal of the Division of Health Psychology, American Psychological Association. 2016;(12):1316-1319
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OBJECTIVE The purpose of this study was to examine whether adults with obesity and metabolic syndrome who screen as high risk for obstructive sleep apnea (OSA) lose less weight as part of a weight loss intervention than those who screen as low risk. METHOD We conducted a secondary analysis of a randomized trial comparing 2 weight loss interventions consisting of dietary counseling for adults with obesity and metabolic syndrome. Participants were screened for sleep apnea using a validated screening questionnaire. Percent weight loss was calculated from weight measured at baseline and intervention end (12 months). Weight loss of 5% or greater was considered clinically significant. Multivariate linear and logistic regression models estimated the association between OSA screening status (high vs. low risk) and percent weight loss and clinically significant weight loss, adjusting for relevant covariates including body mass index and sleep duration. RESULTS Nearly half of participants (45.8%) screened as high risk for OSA. Participants who screened as high risk for OSA lost less weight (1.2% ± 4.2% vs. 4.2% ± 5.3%) and were less likely to lose 5% or greater (24.4% vs. 75.6%) than participants without OSA. CONCLUSION Among adults with obesity and metabolic syndrome, those at high risk for OSA lost less weight in response to a dietary counseling intervention than adults with low risk of OSA. Routine OSA screening should be considered as part of weight loss treatment programs. Additional research is needed to determine how to tailor weight loss treatment for those with high risk for OSA. (PsycINFO Database Record
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[Correlative study of the metabolic disorder of hippocampus and cerebral cortex and cognitive impairment in moderate to severe OSAHS patients].
Wang, B, Xu, X, Liang, G, Zhang, Y, Liu, L, Zhang, J
Lin chuang er bi yan hou tou jing wai ke za zhi = Journal of clinical otorhinolaryngology, head, and neck surgery. 2015;(7):607-11
Abstract
OBJECTIVE To research the serum levels of BDNF, H2S and S-100β as metabolic product of hippocampus and cerebral cortex in moderate to severe obstructive sleep apnea hypopnea syndrome(OSAHS) patients before and after surgery, and to analyze their correlations with cognitive impairment. METHOD Forty-four randomly selected diagnosed OSAHS patients were divided into two groups according to Montreal Cognitive Assessment (MoCA), 19 cases in cognitively normal group and 25 cases in cognitive dysfunction group. Cases in cognitive dysfunction group underwent UPPP oriented surgery, and received 6 months follow-up, 21 cases were remained as treament group, 4 cases lost. 19 cases of healthy subjects were randomly selected as the normal control group. All groups were detected for the serum BDNF, H2S and S-100β levels to analyze the correlations between the biochemical indexes and sleep disorders indexes, hypoxia levels and cognitive function scores. RESULT (1) In the comparison between the treatment group and the normal control group regarding PSG monitoring results, the AHI, I + II, LA/HT and SLT90% indexes of OSAHS patients increased, and the III + IV phase, REM phase, MSaO2 and LSaO2 decreased. In the comparison between the cognitive dysfunction group and the cognitively normal group, the III + IV, REM and LSaO2 indexes of the cognitive dysfunction group decreased. (2) In the comparison between cognitive dysfunction group and cognitively normal group, and between the treatment group and the normal control group, BDNF and H2S levels increased and S-100β levels decreased, and the MoCA total scores, attention, memory/delayed recall scores decreased. (3) The correlation between biochemical indexes with PSG indexes was as follows. The serum BNDF and H2S levels were negatively correlated with AHI index. The serum BNDF and H2S levels were positively correlated with III + IV stage, REM stage and MSaO2 indexes. The S-100β level was positively correlated with AHI index, and S-100β levels were negatively correlated with III + IV stage, REM stage, MSaO2 and LSaO2 indexes. (4) The correlation between biochemical indexes and MoCA scores was as follows. The serum BNDF and H2S levels were positively correlated with MoCA total scores, attention, and memory/delayed recall scores. The serum S-100β levels were negatively correlated with MoCA total scores, attention and memory/ delayed recall scores. (5) The linear regression equation between MoCA total scores in cognitive dysfunction group of OSAHS patients and the serum BNDF, H2S and S-100β levels was as follows: Y(MoCA) = 40.131 + 0.22 X(BDNF) + 0.012 X(H2S)-0.647X(S-100β) (R2 = 0.461). CONCLUSION OSAHS patients with sleep disorder and nocturnal hypoxemia might suffer from cognitive dysfunction in which attention and memory predominates. Serum BNDF, H2S and S-100β levels, which could indirectly reflect the metabolic abnormalities degree of hippocampus and cerebral cortex, are sensitive indicators of early cognitive dysfunction in OSAHS patients.
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Oxidative stress in patients with obstructive sleep apnoea syndrome.
Passali, D, Corallo, G, Yaremchuk, S, Longini, M, Proietti, F, Passali, GC, Bellussi, L
Acta otorhinolaryngologica Italica : organo ufficiale della Societa italiana di otorinolaringologia e chirurgia cervico-facciale. 2015;(6):420-5
Abstract
Obstructive sleep apnoea syndrome (OSAS) is a disorder that leads to metabolic abnormalities and increased cardiovascular risk. The aim of this study was to identify early laboratory markers of cardiovascular disease through analysis of oxidative stress in normal subjects and patients with OSAS. A prospective study was designed to compare outcomes of oxidative stress laboratory tests in 20 adult patients with OSAS and a control group of 20 normal subjects. Laboratory techniques for detecting and quantifying free radical damage must be targeted to assess the pro-oxidant component and the antioxidant in order to obtain an overall picture of oxidative balance. No statistical differences in age, sex distribution, or BMI were found between the two groups (p>0.05). There were significant differences in the apnoea/hypopnoea index (AHI) between OSAS patients and the control group (p<0.05). Statistically significant differences in isoprostane, advanced oxidation protein products (AOPP) and non-protein bound iron (NPBI) levels were found between the study and control groups. No significant difference in the levels of thiol biomarkers was found between the two groups. The main finding of the present study was increased production of oxidative stress biomarkers in OSAS patients. The major difference between thiols and other oxidative stress biomarkers is that thiols are antioxidants, while the others are expressions of oxidative damage. The findings of the present study indicate that biomarkers of oxidative stress in OSAS may be used as a marker of upper airway obstructive episodes due to mechanical trauma, as well as a marker of hypoxaemia causing local oropharyngeal inflammation.
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Diet and exercise improve chemoreflex sensitivity in patients with metabolic syndrome and obstructive sleep apnea.
Maki-Nunes, C, Toschi-Dias, E, Cepeda, FX, Rondon, MU, Alves, MJ, Fraga, RF, Braga, AM, Aguilar, AM, Amaro, AC, Drager, LF, et al
Obesity (Silver Spring, Md.). 2015;(8):1582-90
Abstract
OBJECTIVE Chemoreflex hypersensitity was caused by obstructive sleep apnea (OSA) in patients with metabolic syndrome (MetS). This study tested the hypothesis that hypocaloric diet and exercise training (D+ET) would improve peripheral and central chemoreflex sensitivity in patients with MetS and OSA. METHODS Patients were assigned to: (1) D+ET (n = 16) and (2) no intervention control (C, n = 8). Minute ventilation (VE, pre-calibrated pneumotachograph) and muscle sympathetic nerve activity (MSNA, microneurography) were evaluated during peripheral chemoreflex sensitivity by inhalation of 10% O2 and 90% N2 with CO2 titrated and central chemoreflex by 7% CO2 and 93% O2 for 3 min at study entry and after 4 months. RESULTS Peak VO2 was increased by D+ET; body weight, waist circumference, glucose levels, systolic/diastolic blood pressure, and apnea-hypopnea index (AHI) (34 ± 5.1 vs. 18 ± 3.2 events/h, P = 0.04) were reduced by D+ET. MSNA was reduced by D+ET at rest and in response to hypoxia (8.6 ± 1.2 vs. 5.4 ± 0.6 bursts/min, P = 0.02), and VE in response to hypercapnia (14.8 ± 3.9 vs. 9.1 ± 1.2 l/min, P = 0.02). No changes were found in the C group. A positive correlation was found between AHI and MSNA absolute changes (R = 0.51, P = 0.01) and body weight and AHI absolute changes (R = 0.69, P < 0.001). CONCLUSIONS Sympathetic peripheral and ventilatory central chemoreflex sensitivity was improved by D+ET in MetS+OSA patients, which may be associated with improvement in sleep pattern.
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Effect of CPAP treatment for obstructive sleep apnea hypopnea syndrome on lipid profile: a meta-regression analysis.
Nadeem, R, Singh, M, Nida, M, Kwon, S, Sajid, H, Witkowski, J, Pahomov, E, Shah, K, Park, W, Champeau, D
Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine. 2014;(12):1295-302
Abstract
STUDY OBJECTIVE Patients with obstructive sleep apnea (OSA) frequently exhibit higher rates of dyslipidemia, a risk factor for cardiovascular and cerebrovascular disorders. Treatment for OSA by CPAP may improve cholesterol metabolism. This meta-regression analysis (MA) estimates the effect of CPAP treatment on dyslipidemia. METHODS PubMed and Cochrane libraries were searched by utilizing different combinations of keywords: CPAP, obstructive sleep apnea, serum lipids, dyslipidemia, cholesterol, total cholesterol (TC), low density lipoprotein, LDL, high density lipoprotein, HDL, triglyceride, and TG. Inclusion criteria were: (1) English articles and (2) studies with an adult population with the diagnosis of OSA who were treated with CPAP. The OSA group must have cholesterol profile including TC, LDLc, HDLc, and TG, without and with CPAP treatment. Fifty-four studies were reviewed, while 29 studies pooled for MA. RESULTS Thirty-four datasets from 29 studies with 1,958 subjects pooled. Treatment duration range was from 2 days to 1 year. TC standardized mean differences (SMD) ranged from -41.5 to -0.077, pooled mean difference (PMD) was -5.660 (LL -6.715 to UL -4.606, p < 0.001). SMD in LDL ranged from -3.7 to 0; PMD was -0.488 (LL -0.715 to UL -0.261, p < 0.001). HDL SMD ranged from -0.498 to 1.94. The PMD was 0.207 (LL 0.05 to UL 0.364, p < 0.01). TG SMD ranged from -9.327 to 1.98; PMD was -0.054 (LL -0.124 to UL 0.016, p < 0.129). CONCLUSIONS CPAP treatment for OSA seems to improve dyslipidemia (decrease in total cholesterol and LDL, and increase in HDL). It does not appear to affect TG levels.