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Identifier 000440882
Title Η Αποφρακτική Υπνική Άπνοια (Σ.Α.Υ.) σε μετεμμηνοπαυσιακές γυναίκες και μεσήλικες μη-παχύσαρκους άνδρες. / Ήλια Κρητικού ; επιβλέπων καθηγητής, Αλέξανδρος Ν. Βγόντζας.
Alternative Title Osa in postmenopausal women and non-obese middle aged men
Author Κρητικού, Ήλια
Thesis advisor Βγόντζας, Αλέξανδρος Ν.
Reviewer Χρούσος, Γεώργιος
Σιαφάκας, Νικόλαος
Μπάστα, Μαρία
Ξεκούκη, Παρασκευή
Σίμος, Παναγιώτης
Σχίζα Σοφία
Abstract Obstructive sleep apnoea (OSA), is most frequent in obese middle-aged males, however its prevalence in females has been steadily increasing, and it peaks post-menopause. According to studies there is significant overlap of symptoms and comorbid disorders that accompany obesity and sleep apnea, since the majority of OSA patients are obese. More specifically, in obese male patients, OSA has been associated with visceral obesity, chronic low grade inflammation and insulin resistance. This complicated relationship resembles the “chicken or the egg” causality dilemma where the underlying pathophysiology is too difficult to disentangle. Important information could be provided by studies performed on non-obese patients with apnea but data so far has been scarce. Additionally, due to the paucity of information on non-obese apneic patients, it has been postulated that anatomic factors, such as local stenosis of the upper extrathoracic airways is the major contributing factor rather than visceral obesity and chronic inflammation. Moreover, it is unclear whether currently available therapies, such as the continuous positive airway pressure (CPAP), which is the mainstay treatment modality for OSA, can improve the symptoms and the cardiovascular morbidity that accompany OSA. OSA is characterised by repetitive episodes of upper airway obstruction leading to complete airflow cessation (apnoea) or partial airflow reduction (hypopnea) during sleep, that result in intermittent hypoxaemia, electroencephalographic arousals and sleep fragmentation. The associated hypoxaemia and the concomitant increase in arterial carbon dioxide tension are expected to result in sympathetic activation and catecholamine secretion, while the repeated arousals can cause activation of the hypothalamic–pituitary–adrenal (HPA) axis, thus increasing cortisol release. However, previous findings on the association of obstructive sleep apnoea (OSA) and the hypothalamic–pituitary–adrenal (HPA) axis are inconsistent, partly due to the confounding effect of obesity and infrequent sampling. In the current study our goal is to examine whether in a relatively nonobese population, OSA is associated with visceral fat, sleepiness and inflammation/insulin resistance as well as elevated cortisol levels. Secondary goal is to assess the effects of a 2-month placebo-controlled (sham-CPAP) continuous positive airway pressure (CPAP) use. The participants were middle-aged men and postmenopausal women and their gender-matched controls, and they were studied in the sleep laboratory for four nights. Measures of sleepiness (objective and subjective), performance, serial 24-h blood samples for interleukin (IL)-6, tumour necrosis factor receptor (TNFR)-1, leptin and adiponectin and cortisol, and single blood samples for high-sensitivity C-reactive protein (hsCRP), fasting lipids, fasting glucose and insulin levels were obtained. Abdominal (visceral (VAT), subcutaneous (SAT) adipose tissue) and liver fat were assessed with computed tomography. OSA patients were re-assessed following the same protocol post-CPAP and post sham-CPAP. Apnoeic males were significantly sleepier and had significantly higher hsCRP, IL-6, leptin and insulin resistance than controls. Apnoeic females had significantly higher hsCRP; however, objective sleepiness, IL-6, TNFR-1, insulin resistance (Homeostatic Model Assessment index), leptin and adiponectin were similar to controls. Apnoeic males had significantly higher VAT than controls, while apnoeic females had higher SAT than controls. In both sexes, OSA was associated with increased liver fat. Finally, in both apnoeic men and women, OSA was associated with significantly higher 24-h cortisol levels compared with gender matched controls. CPAP lowered cortisol levels significantly and improved subjective sleepiness, but no changes were observed in any of the inflammation/insulin resistance biomarkers. Finally, CPAP did not affect abdominal and liver fat. In conclusion, in non-obese apnoeic men and slightly obese postmenopausal women, OSA is associated with the metabolic syndrome, increased daytime sleepiness, inflammation and insulin resistance and this association is stronger in males than in females. Moreover in overweight males, OSA is associated with visceral adiposity whereas in females with global adiposity. Finally both genders exhibit significantly higher 24-h cortisol levels compared with controls. CPAP treatment, at least in the short-term, seems to improve objective sleep quality and lower cortisol levels, and thus may have a beneficial effect on cardiovascular morbidity such as hypertension. However this effect is partial since CPAP does not seem to affect the chronic inflammation and metabolic dysregulation that accompany OSA. Thus it is recommended that CPAP is combined with other treatment modalities targeting these disorders, including healthy diet, physical activity, anti-inflammatory medications and medications that improve insulin sensitivity. Our findings also underline the need for gender-specific therapeutic interventions. For example in men, target visceral fat accumulation through exercise and specific diet may be appropriate, while in women overall weight and fat loss may be beneficial.
Language Greek
Subject Cortisol
Fatty liver
Θεραπεία μάσκας
Issue date 2021-07-30
Collection   School/Department--School of Medicine--Department of Medicine--Doctoral theses
  Type of Work--Doctoral theses
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