Pathophysiological parameters of obstructive sleep arnoea syndrome

Introduction: Obstructive Sleep Apnea (OSA) is one of the most widespreadsyndromes with sufferers from all ages. It is also known that OSA is directlylinked to obesity, as well as the incidence of Metabolic Syndrome (MS).Nevertheless, according to the bibliography on the subject, it is not clear whether the pathophysiological changes occurring to OSA patients are solely attributableto it irrespective of obesity or MS.Purpose: The aim of the study is to investigate the correlation of OSA, whethermild or severe, as it is expressed by the ΑΗΙ indicator, with somatometric data(cervice, hip, abdomen and hip perimeters), with obesity-generating fat tissuehormones, with sex/gender hormones, with thyroid gland hormones, with theIGFBP-1 growth factor, with inflammation indicators, with resistance toinsoulin, with hyperlipidemia, as well as Metabolic Syndrome characteristics.Material – Method: In the study, participated 131 patients (111 male, 21female), average age 55.4±12.4, average body mass index 34.3±11.2kg/m2 andaverage AHI indicator 44.7±26.3. Of those 131 patients, 75 (57.25%) sufferedfrom Metabolic Syndrome (according to ATP III criteria), while 56 (42.75%) didnot. Cervice, hip, abdomen and thigh perimeters were measured on all patients.Moreover, there were measurements of CRP, fibrinogen, ferritin, uric acid,cholesterol, triglycerides, HDL, glucose, insoulin, T3, free thyroxine, thyroidstimulating hormone, X-linked globin, sulfate dehydroepiandrosterone andtestosterone. Additionally, insoulin resistance was calculated through theHOMA-IR indicator. Finally, in 111 (95 male, 16 female) of the 131 patients,adinopectin, leptin and IGFBP-1 levels were measured.The participants were divided into two groups, those suffering only fromOSA, and those suffering from OSA and MS at the same time. Results: The results of the OSA correlations with the above parameters are asfollows:• AHI is correlated with BMI, cervice, hip, thigh and abdomen perimeters. Ofall the above correlations, cervice perimeter constitutes the determiningfactor of the OSA severity.• T3, FT4 and TSH figures are not affected in OSA sufferers. Consequently,the impact of hypothyroidism on OSA patients is low.• Uric acid levels are independent of the OSA indicator and are mostlyaffected by male gender and hemoglobin saturation on OSA patients withhigh levels of uric acid.• Obesity is linked / correlated to increased leptin levels, as well as lowIGFBP-1 levels, while OSA is only linked to low IGFBP-1 levels. Leptin isnot related to OSA.• Insoulin resistance (as measured through the HOMA-IR indicator) is loweron milder OSA sufferers (as expressed through AHI) AHI20.• No correlation between the HOMA-IR indicator and obesity was found. No correlation among adinopectin, obesity and OSA was found. OSA patients’ testosterone levels are inversrely proportionate to body massindex (R2: 0.290; p:0.01). Age and OSA indicator are unrelated totestosterone levels.• Inflammation indicators (ferritin, fibrinogen, CRP) are increased in OSApatients, irrespective of Metabolic Syndrome coexistence. Ferritin,however, (p20.Conclusions:• The perimeter of the cervice determines the severity of the OSA syndrome.• The effect of hypothyroidism on OSA patients is low, and therefore, noneed to measure thyroid hormones in all sufferers arises.• It is hypoxia rather than AHI that affects uric acid levels on OSA sufferers.• OSA is related to lower levels of IGFBP-1.• Leptin and adiponectin are not related to OSA.• Leptin levels drop with obesity. There was no correlation betweenadiponectin and obesity.• Resistance to insoulin depends on the severity of the OSA syndrome and on MS. No correlation between resistance to insoulin and obesity was found.• Testosterone levels are not related to OSA, but to the body mass index. Moreover, they are lower in patients suffering from both OSA and MS thanin those suffering from OSA alone. Consequently, the diminished libidofrequently mentioned by OSA patients is attributable to obesity rather thanOSA.• OSA increases inflammatory indicators regardless of MS.• Ferritin levels are higher in OSA and MS patients.• OSA is not related to hyperlipidemia, yet OSA and MS sufferers tend todevelop it as compared to those suffering from OSA alone.• SHGB and DHEAS are not related to either OSA or MS.• Ηoma-IR is related to the severity of OSA (increases when AHI>20).Εισαγωγή: Το σύνδρομο άπνοιας στον ύπνο (ΣΑΥ) είναι μία από τις, πλέον,διαδεδομένες νόσους και συναντάται σε ένα ευρύτατο φάσμα ηλικιών. Είναι,επίσης, γνωστό ότι το ΣΑΥ συνδέεται με την παχυσαρκία, καθώς και με τηνεμφάνιση Μεταβολικού Συνδρόμου (ΜΣ). Όμως, σύμφωνα με τη βιβλιογραφία,δεν είναι σαφές αν κάποιες από τις παθοφυσιολογικές αλλαγές που εμφανίζονταιστους ασθενείς με ΣΑΥ οφείλονται στο ΣΑΥ, ανεξάρτητα της παχυσαρκίας ήτου μεταβολικού συνδρόμου.Σκοπός: Σκοπός της μελέτης είναι να διερευνήσει τη συσχέτιση της υπνικήςάπνοιας, ποικίλης βαρύτητας, όπως αυτή εκφράζεται από τον υπνο-απνοϊκόδείκτη, με τα σωματομετρικά δεδομένα (περίμετρος τραχήλου, ισχίου, κοιλίας,μηρών) με ορμόνες του λιπώδους ιστού που προάγουν την παχυσαρκία, με τιςφυλετικές ορμόνες, με τις ορμόνες του θυρεοειδούς αδένα, με τον αυξητικόπαράγοντα IGFBP-1 με δείκτες φλεγμονής, με την αντίσταση στην ινσουλίνη, μετην υπερλιπιδαιμία, καθώς και με χαρακτηριστικά του Μεταβολικού Συνδρόμου (ΜΣ).Υλικό-Μέθοδος: Συμμετείχαν συνολικά 131 ασθενείς (110 άνδρες, 21γυναίκες), μέσος όρος ηλικίας 55.4±12.4, μέσος δείκτης μάζας σώματος34.3±11.2kg/m2 και μέσος δείκτης απνοιών-υποπνοιών ΑΗΙ 44.7±26.3. Από τους 131 ασθενείς οι 75 (57.25%) παρουσίασαν μεταβολικό σύνδρομο (σύμφωνα μετα κριτήρια του ΑΤΡ ΙΙΙ) και οι 56 (42.75%) όχι. Σε όλους τους ασθενείςυπολογίστηκε η περίμετρος τραχήλου, ισχίου, μηρού και κοιλιάς. Επιπλέον,μετρήθηκαν η CRP, το ινωδογόνο, η φερριτίνη, το ουρικό οξύ, η χοληστερόλη,τα τριγλυκερίδια, η HDL, η γλυκόζη, η ινσουλίνη, η ολική τριιωδοθυρονίνη, ηελεύθερη θυροξίνη, η θυρεοειδοτρόπος ορμόνη, η φυλοσυνδετική σφαιρίνη, ηθειϊκή δεϋδροεπιανδροστερόλη και η τεστοστερόνη. Υπολογίστηκε, επίσης, ηαντίσταση στην ινσουλίνη μέσω του δείκτη HOMA-IR. Tέλος, σε 111 (95άνδρες, 16 γυναίκες), από τους 131 ασθενείς, μετρήθηκαν τα επίπεδααδιπονεκτίνης, λεπτίνης και IGFBP-1.Οι ασθενείς χωρίστηκαν σε δύο ομάδες, σε αυτούς που είχαν μόνο ΣΑΥ καισε αυτούς που εμφάνιζαν ταυτόχρονα ΣΑΥ και ΜΣ.Αποτελέσματα: Τα αποτελέσματα των συσχετίσεων του ΣΑΥ με τις παραπάνωπαραμέτρους φαίνονται παρακάτω:• Ο ΑΗΙ συσχετίζεται με τον BMI, την περίμετρο του τραχήλου, τηνπερίμετρο του ισχίου, την περίμετρο του μηρού και την περίμετρο τηςκοιλίας. Από όλους τους παραπάνω συσχετισμούς, η περίμετρος τουτραχήλου είναι ο κύριος καθοριστικός παράγων για το μέγεθος του υπνο-απνοϊκού δείκτη.• Οι τιμές της ολική τριιωδοθυρονίνης (T3), της ελεύθερης θυροξίνης (FT4)και της θυρεοειδοτρόπος ορμόνης (TSH) δεν επηρεάζονται στους ασθενείςμε ΣΑΥ. Ως εκ τούτου, η επίπτωση του υποθυρεοειδισμού σε ασθενείς μευπνική άπνοια είναι χαμηλή. Τα επίπεδα του ουρικού οξέως είναι ανεξάρτητα από τον δείκτη απνοιών-υποπνοιών και επηρεάζονται από το άρρεν φύλο και τον κορεσμό τηςαιμοσφαιρίνης στους ασθενείς με ΣΑΥ που εμφανίζουν αυξημένο ουρικόοξύ.• H παχυσαρκία σχετίζεται με αυξημένα επίπεδα λεπτίνης και μειωμέναεπίπεδα μόνον του IGFBP-1, ενώ το ΣΑΥ σχετίζεται με μειωμένα επίπεδαIGFBP-1. Η λεπτίνη δεν σχετίζεται με το ΣΑΥ.• Η αντίσταση στην ινσουλίνη, έτσι όπως υπολογίστηκε από τον δείκτηHOMA-IR, είναι μειωμένη στους ασθενείς που παρουσιάζουν ηπιότεροΣΑΥ (όπως αυτό εκφράζεται από τον ΑΗΙ) ΑΗΙ20.• Δεν βρέθηκε κάποια συσχέτιση του δείκτη HOMA-IR με την παχυσαρκία.• Δεν βρέθηκε συσχέτιση μεταξύ αδιπονεκτίνης, παχυσαρκίας και ΣΑΥ.• Τα επίπεδα τεστοστερόνης στους ασθενείς με ΣΑΥ σχετίζονται αντιστρόφως ανάλογα με τον δείκτη μάζας σώματος (R2: 0.290; p:0.01). Ηηλικία και ο δείκτης απνοιών-υποπνοιών δεν σχετίζονται με τα επίπεδατεστοστερόνης.• Οι δείκτες φλεγμονής (φερριτίνη, ινωδογόνο, CRP), στους ασθενείς μεΣΑΥ, είναι αυξημένοι, ανεξάρτητα από την συνύπαρξη ή μη μεταβολικούσυνδρόμου. Η φερριτίνη, όμως, (p20, δεν σχετίζεται με τον υποθυρεοειδισμό, δεν σχετίζεται με την λεπτίνη και την αδιπονεκτίνη, δεν σχετίζεται με τα επίπεδα του ουρικού οξέως, δεν σχετίζεται με χαμηλά επίπεδα τεστοστερόνης, δεν σχετίζεται με την SHBG και την DHEAS, δεν σχετίζεται με την υπερλιπιδαιμία

Association between Patient- and Partner-Reported Sleepiness Using the Epworth Sleepiness Scale in Patients with Obstructive Sleep Apnoea

Excessive daytime sleepiness in obstructive sleep apnoea (OSA) is often measured differently by patients and their partners. This study investigated the association between patient- and partner-completed Epworth Sleepiness Scale (ESS) scores and a potential correlation with OSA severity. One hundred two participants, 51 patients and 51 partners, completed the ESS before and three months after initiating CPAP treatment. There was no significant difference when comparing patients’ and partners’ ESS scores at baseline (10.75 ± 5.29 vs. 11.47 ± 4.96, respectively) and at follow-up (6.04 ± 4.49 vs. 6.41 ± 4.60, respectively). There was a strong correlation between patients’ and partners’ ESS scores on both (baseline and follow-up) assessments (p < 0.001). There was significant improvement in patients’ and partners’ ESS scores after CPAP therapy (p < 0.001). There was no significant difference in patients’ or partners’ ESS scores between patients with mild, moderate or severe OSA. There was no significant correlation between oxygen desaturation index (ODI) and ESS score reported either by patient or by partner. In conclusion, our study revealed a strong correlation between patient- and partner-reported ESS scores. However, neither patient- nor partner-completed ESS scores were associated with OSA severity

Nasal Symptoms in Patients with Obstructive Sleep Apnoea and Their Association with Continuous Positive Airway Pressure Usage

The role of nasal symptoms in continuous positive airway pressure (CPAP) tolerance is not completely clear. This study aimed to investigate the association between CPAP usage and nasal symptoms, either prior to, or developing during, CPAP use in patients with obstructive sleep apnoea (OSA). Two hundred thirty patients were studied and divided into high-, low-, and non-CPAP users. Nasal symptoms and related quality of life parameters were evaluated prior to CPAP initiation and after three months. We also investigated predictive factors for CPAP usage. Non-CPAP users had significantly worse baseline scores for runny nose compared with high and low users (1.34 vs. 0.68 and 0.75, respectively, p = 0.006). There were no other significant differences between the groups. Runny nose was an independent predictive factor for lower CPAP usage (p = 0.036). An evaluation after three months showed worsening in runny nose score in high-CPAP users (p = 0.025) but not in low- and non-users. There were no significant changes in other nasal symptoms. Our study demonstrates that nasal symptoms were very common in this population but rhinorrhoea was the only symptom associated with poorer CPAP adherence. Moreover, rhinorrhoea worsened after a three-month trial of high-CPAP usage

Improvements in Plasma Tumor Necrosis Factor-Alpha Levels after a Weight-Loss Lifestyle Intervention in Patients with Obstructive Sleep Apnea

Obstructive sleep apnea (OSA) and systemic inflammation typically coexist within a vicious cycle. This study aimed at exploring the effectiveness of a weight-loss lifestyle intervention in reducing plasma tumor necrosis factor-alpha (TNF-a), a well-established modulator of systematic inflammation in OSA. Eighty-four adult, overweight patients with a diagnosis of moderate-to-severe OSA were randomized to a standard care (SCG, n = 42) or a Mediterranean lifestyle group (MLG, n = 42). Both groups were prescribed continuous positive airway pressure (CPAP), while the MLG additionally participated in a 6-month behavioral intervention aiming at healthier weight and lifestyle habits according to the Mediterranean pattern. Plasma TNF-a was measured by an immunoenzymatic method both pre- and post-intervention. Drop-out rates were 33% (n = 14) for the SCG and 24% (n = 10) for the MLG. Intention-to-treat analysis (n = 84) revealed a significant decrease in median TNF-a only in the MLG (from 2.92 to 2.00 pg/mL, p = 0.001). Compared to the SCG, the MLG exhibited lower follow-up TNF-a levels (mean difference adjusted for age, sex, baseline TNF-a and CPAP use: −0.97 pg/mL, p = 0.014), and further controlling for weight loss did not attenuate this difference (p = 0.020). Per protocol analyses (n = 60) revealed similar results. In conclusion, a healthy lifestyle intervention can lower plasma TNF-a levels in patients with OSA

Cardiometabolic Benefits of a Weight-Loss Mediterranean Diet/Lifestyle Intervention in Patients with Obstructive Sleep Apnea: The “MIMOSA” Randomized Clinical Trial

Although continuous positive airway pressure (CPAP) is the first-line treatment for obstructive sleep apnea (OSA), its cardiometabolic benefits are questionable. Our aim was to explore whether the combination of a weight-loss Mediterranean diet/lifestyle intervention with OSA standard care leads to greater cardiometabolic improvements compared with standard care alone. We randomly assigned 187 adult, overweight, polysomnography-diagnosed moderate-to-severe OSA patients to a standard care group (SCG, n = 65), a Mediterranean diet group (MDG, n = 62) or a Mediterranean lifestyle group (MLG, n = 60). All three groups were prescribed with CPAP. Additionally, the SCG only received brief written healthy lifestyle advice, while intervention arms were subjected to a six-month weight-loss behavioral intervention based on the Mediterranean diet. The MLG also received guidance for improving physical activity and sleep habits. Glucose metabolism indices, blood lipids, liver enzymes and blood pressure improved only in intervention arms, and were significantly lower compared to the SCG post-intervention (all p < 0.05). The age-, sex-, baseline- and CPAP use-adjusted relative risk (95% confidence interval) of metabolic syndrome was 0.58 (0.34–0.99) for the MDG and 0.30 (0.17–0.52) for the MLG compared to the SCG. The MLG additionally presented a lower relative risk of metabolic syndrome compared to the MDG (0.52 (0.30–0.89)). After further adjustment for body-weight change, a lower relative risk of metabolic syndrome was still evident for the MLG compared to the SCG. In conclusion, although standard care alone does not improve OSA patients’ cardiometabolic profile, its combination with a weight-loss Mediterranean diet/lifestyle intervention leads to significant cardiometabolic benefits

Associations between Vitamin D Status and Polysomnographic Parameters in Adults with Obstructive Sleep Apnea

Vitamin D deficiency (VDD) may be associated with obstructive sleep apnea (OSA) presence and is more pronounced with increasing OSA severity; however, the relationship between these two entities remains unclear. This was a cross-sectional study among 262 adults with in-hospital-attended polysomnography-diagnosed OSA and no additional major comorbidities, aiming to explore possible associations between serum 25-hydroxyvitamin D [25(OH)D] levels and polysomnographic parameters. Data on demographics, medical history, anthropometric indices, and lifestyle habits were collected at enrolment. Serum 25(OH)D was evaluated using chemiluminescence, with VDD defined as 25(OH)D p 2 [3.38 (1.52–7.52)], but not in the younger and non-obese adults. This study provides further evidence of an inverse association between vitamin D levels and OSA severity and underscores the importance of considering vitamin D status as a potential modifiable factor in the comprehensive management of OSA

Cardiometabolic Benefits of a Weight-Loss Mediterranean Diet/Lifestyle Intervention in Patients with Obstructive Sleep Apnea: The “MIMOSA” Randomized Clinical Trial

Although continuous positive airway pressure (CPAP) is the first-line treatment for obstructive sleep apnea (OSA), its cardiometabolic benefits are questionable. Our aim was to explore whether the combination of a weight-loss Mediterranean diet/lifestyle intervention with OSA standard care leads to greater cardiometabolic improvements compared with standard care alone. We randomly assigned 187 adult, overweight, polysomnography-diagnosed moderate-to-severe OSA patients to a standard care group (SCG,n= 65), a Mediterranean diet group (MDG,n= 62) or a Mediterranean lifestyle group (MLG,n= 60). All three groups were prescribed with CPAP. Additionally, the SCG only received brief written healthy lifestyle advice, while intervention arms were subjected to a six-month weight-loss behavioral intervention based on the Mediterranean diet. The MLG also received guidance for improving physical activity and sleep habits. Glucose metabolism indices, blood lipids, liver enzymes and blood pressure improved only in intervention arms, and were significantly lower compared to the SCG post-intervention (allp< 0.05). The age-, sex-, baseline- and CPAP use-adjusted relative risk (95% confidence interval) of metabolic syndrome was 0.58 (0.34-0.99) for the MDG and 0.30 (0.17-0.52) for the MLG compared to the SCG. The MLG additionally presented a lower relative risk of metabolic syndrome compared to the MDG (0.52 (0.30-0.89)). After further adjustment for body-weight change, a lower relative risk of metabolic syndrome was still evident for the MLG compared to the SCG. In conclusion, although standard care alone does not improve OSA patients’ cardiometabolic profile, its combination with a weight-loss Mediterranean diet/lifestyle intervention leads to significant cardiometabolic benefits

The effectiveness of a weight-loss Mediterranean diet/lifestyle intervention in the management of obstructive sleep apnea: Results of the ? MIMOSA ? randomized clinical trial

Background & aims: Although continuous positive airway pressure (CPAP) is the first-line treatment for obstructive sleep apnea (OSA), lifestyle interventions have also emerged as complementary therapeutic choices. We aimed to explore whether the addition of a weight-loss Mediterranean diet/lifestyle inter-vention to OSA standard care, i.e. CPAP prescription and brief written healthy lifestyle advice, has an incremental effect on improving OSA severity, over the effect of standard care alone. Methods: We designed a parallel, randomized, controlled, superiority clinical trial. Eligible participants were adult, overweight men and women, diagnosed with moderate-to-severe OSA [apnea-hypopnea index (AHI)> 15 events/h] through an attended overnight polysomnography. Participants were blindly randomized to a standard care group (SCG, n = 65), a Mediterranean diet group (MDG, n = 62) or a Mediterranean lifestyle group (MLG, n = 60). All three study groups were prescribed with CPAP. The SCG additionally received written healthy lifestyle advice, while intervention arms were subjected to a 6-month behavioral intervention aiming at weight loss and increasing adherence to the Mediterranean diet. The MLG also received counselling on physical activity and sleep habits. Polysomnographic data and OSA symptoms were evaluated pre-and post-intervention. Results: A total of 187 OSA patients were recruited. Seven patients were excluded post-randomization and 53/180 (29%) were lost to follow-up. No harms from the interventions applied were reported. Ac-cording to intention-to-treat analysis (n = 180), mean (95% confidence interval) AHI change was-4.2 (-7.4,-1.0) for the SCG,-24.7 (-30.4,-19.1) for the MDG and-27.3 (-33.9,-20.6) for the MLG. Post-intervention age-, sex-, baseline-and CPAP use-adjusted AHI was significantly lower in the MDG and the MLG compared to the SCG (mean difference:-18.0, and-21.2, respectively, both P < 0.001), and the differences remained significant after further adjustment for body-weight change (P = 0.004 and 0.008, respectively). Other respiratory event indices, daytime sleepiness and insomnia were also significantly lower in both intervention arms compared to the SCG (all P < 0.05). The MLG only presented higher percent rapid-eye-movement sleep and lower daytime sleepiness compared to the MDG (both P < 0.05). Results were similar in the per-protocol analysis (n = 127). Conclusions: A dietary/lifestyle intervention on top of standard care leads to greater improvements in OSA severity and symptomatology compared to standard care alone. Benefits are evident regardless of CPAP use and weight loss. Trial registration: Clinicaltrials.gov NCT02515357, https://clinicaltrials.gov/ct2/show/NCT02515357. (c) 2020 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved

A weight-loss Mediterranean diet/lifestyle intervention ameliorates inflammation and oxidative stress in patients with obstructive sleep apnea: results of the “MIMOSA” randomized clinical trial

Purpose Inflammation and oxidative stress are implicated in obstructive sleep apnea (OSA) pathophysiology. We aimed at exploring whether the combination of a weight-loss Mediterranean diet/lifestyle intervention with OSA standard care, i.e., continuous positive airway pressure (CPAP) prescription, can lead to greater improvements in inflammation and oxidative stress, compared to standard care alone. Methods This was a randomized controlled clinical trial in 187 adult, overweight patients with moderate-to-severe OSA. Participants were randomized to a standard care (SCG, n = 65), a Mediterranean diet (MDG, n = 62) or a Mediterranean lifestyle group (MLG, n = 60). All groups received OSA standard care. Intervention arms participated in a 6-month behavioral weight-loss intervention based on the Mediterranean diet, while the MLG also received counselling on physical activity and sleep habits. Results Seven patients were excluded and 53/180 were lost to follow-up. In intention to treat analysis (n = 180), the SCG did not exhibit changes in any of the markers assessed. Post-intervention age-, sex-, baseline- and CPAP use-adjusted plasma high sensitivity C-reactive protein levels (mg/L) were lower in the MDG and the MLG compared to the SCG (mean difference - 1.33, P = 0.039 and - 1.68, P = 0.007, respectively). The MLG also exhibited lower urinary 8-iso prostaglandin F2a levels (ng/mg creatinine) compared to the SCG and the MDG (mean difference - 1.10, P < 0.0001 and - 0.80, P = 0.001, respectively). Adiponectin and oxidized guanine levels were not altered in any of the study groups. Results were similar in per protocol analysis (n = 127). Conclusion A weight-loss Mediterranean diet/lifestyle intervention on top of CPAP has anti-inflammatory and antioxidant benefits in OSA. Registration The trial was prospectively registered at ClinicalTrials.gov (NCT02515357) on August 4, 2015