Obstructive sleep apnea and metabolic dysfunction in polycystic ovary syndrome

Obstructive sleep apnea (OSA) is an underrecognized, yet significant factor in the pathogenesis of metabolic derangements in polycystic ovary syndrome (PCOS). Recent findings suggest that there may be two "subtypes" of PCOS, i.e. PCOS with or without OSA, and these two subtypes may be associated with distinct metabolic and endocrine alterations. PCOS women with OSA may be at much higher risk for diabetes and cardiovascular disease than PCOS women without OSA and may benefit from therapeutic interventions targeted to decrease the severity of OSA. The present chapter will review what is currently known about the roles of sex steroids and adiposity in the pathogenesis of OSA, briefly review the metabolic consequences of OSA as well as the metabolic abnormalities associated with PCOS, review the prevalence of OSA in PCOS and finally present early findings regarding the impact of treatment of OSA on metabolic measures in PCOS.     

Relationships between sleep disordered breathing and glucose metabolism in polycystic ovary syndrome

CONTEXT: Women with polycystic ovary syndrome (PCOS) are insulin resistant and are at increased risk for sleep apnea, which, in turn, may contribute to insulin resistance. OBJECTIVE: The objective of this study was to determine relationships between risk and severity of obstructive sleep apnea (OSA) and glucose metabolism in PCOS. DESIGN AND SETTING: This study included two cohorts of women with PCOS in a tertiary care hospital. PATIENTS AND MAIN OUTCOME MEASURES: Cohort 1 included 40 nondiabetics who completed the Epworth Sleepiness Scale, the Pittsburgh Sleep Quality, and the Berlin Questionnaire to assess risk of OSA; 32 of the 40 women had an oral glucose tolerance test. Cohort 2 included eight women who had a sleep study, glycosylated hemoglobin level, and an oral glucose tolerance test. RESULTS: In cohort 1, 62.5% of the women had poor sleep quality by Pittsburgh Sleep Quality Index, and 18 (45%) had chronic daytime sleepiness by Epworth Sleepiness Scale. Thirty of the 40 women had a high risk of OSA by Berlin Questionnaire. Women with high OSA risk had higher fasting insulin levels and homeostasis model assessment index compared with those with low OSA risk (168.2 +/- 17.3 vs. 97.2 +/- 6.4 pmol/liter, P = 0.011; 6.3 +/- 0.7 vs. 3.6 +/- 0.3 mg/dl x microU/ml, P = 0.014, respectively). Among women with normal glucose tolerance, insulin levels were significantly higher in those at high vs. low OSA risk, independently of body mass index. Women in cohort 2 had rapid eye movement (REM)-predominant OSA with lower sleep efficiency, longer sleep latency, and less REM sleep than controls. Glycosylated hemoglobin levels and the area under the glucose curve positively correlated with the apnea-hypopnea index (rP = 0.82, P = 0.013; rP = 0.96, P = 0.0008, respectively) and the number of oxygen desaturations in REM sleep (rP = 0.97, P = 0.0009; rP = 0.97, P = 0.005, respectively). CONCLUSION: PCOS is associated with poor sleep quality, daytime sleepiness, and increased risk for OSA. Insulin levels and measures of glucose tolerance in PCOS are strongly correlated with the risk and severity of OSA.     

Increased prevalence of obstructive sleep apnea syndrome in obese women with polycystic ovary syndrome

Obstructive Sleep Apnea (OSA) is considerably more common in men than women. Preliminary data suggest that androgens may play a role in the male predominance of apnea. Polycystic Ovary Syndrome (PCOS) is characterized by menstrual disturbances, androgen excess, and frequently obesity. These features suggest that women with PCOS may be at increased risk for OSA. To determine whether obese women with PCOS have an increased prevalence of sleep apnea compared with age and weight-matched reproductively normal women, we performed overnight polysomnography for determination of the apnea-hypopnea index (AHI) in 18 obese women with PCOS and age and weight-matched control women. Additional measurements included waist, hip, and neck circumferences, serum total testosterone, unbound testosterone, and DHEAS. Women with PCOS had a higher AHI than controls (22.5 +/- 6.0, vs. 6.7 +/- 1.0, P = 0.008). Women with PCOS were also more likely to suffer from symptomatic OSA syndrome (44.4% vs. 5.5%, P = 0.008). AHI correlated with waist-hip ratio (r = 0.51, P < 0.03), serum testosterone (r = 0.52, P < 0.03) and unbound testosterone (r = 0.50, P < 0.05) in women with PCOS. We conclude that obese women with PCOS are at increased risk of OSA when compared with matched reproductively normal women. Women with PCOS should be carefully questioned regarding symptoms of sleep apnea.     

Obstructive sleep apnoea and polycystic ovary syndrome: A comprehensive review of clinical interactions and underlying pathophysiology

Polycystic ovary syndrome (PCOS) is the most prevalent endocrine disorder in women of reproductive age. PCOS is associated with multiple comorbidities including, obesity, insulin resistance and type 2 diabetes, as well as mood disorders and impaired quality of life (QoL). Obstructive sleep apnoea (OSA) is also a common medical condition that is often undiagnosed, particularly in women. OSA is associated with a similar spectrum of comorbidities to that observed in PCOS, including manifestations of the metabolic syndrome and impaired QoL, whilst obesity frequently constitutes a common denominator in the pathophysiology of both OSA and PCOS. Hence, it is not surprising that OSA and PCOS may coexist in women of reproductive age, and the current clinical guidelines on the management of PCOS recommend screening for OSA symptoms in overweight/obese women with PCOS. In this review, we examine the relationship between OSA and PCOS and explore the potential underlying mechanisms that link these two conditions.     

Polycystic ovary syndrome is associated with obstructive sleep apnea and daytime sleepiness: role of insulin resistance

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder of premenopausal women, characterized by chronic hyperandrogenism, oligoanovulation, and insulin resistance. Obstructive sleep apnea (OSA) and excessive daytime sleepiness (EDS) are strongly associated with insulin resistance and hypercytokinemia, independently of obesity. We hypothesized that women with PCOS are at risk for OSA and EDS. Fifty-three women with PCOS (age range, 16-45 yr) and 452 control premenopausal women (age range, 20-42), from a general randomized sample for the assessment of prevalence of OSA, were evaluated in the sleep laboratory for 1 night. In addition, women with PCOS were tested for plasma free and weakly bound testosterone, total testosterone, and fasting blood glucose and insulin concentrations. In this study, PCOS patients were 30 times more likely to suffer from sleep disordered breathing (SDB) than the controls [odds ratio = 30.6, 95% confidence interval (7.2-139.4)]. Nine of the PCOS patients (17.0%) were recommended treatment for SDB, in contrast with only 3 (0.6%) of the control group (P < 0.001). In addition, PCOS patients reported more frequent daytime sleepiness than the controls (80.4% vs. 27.0%, respectively; P < 0.001). PCOS patients who were recommended treatment for SDB, compared with those who were not, had significantly higher fasting plasma insulin levels (306.48 +/- 52.39 vs. 176.71 +/- 18.13 pmol/L, P < 0.01) and a lower glucose-to-insulin ratio (0.02 +/- 0.00 vs. 0.04 +/- 0.00, P < 0.05). Plasma free and total testosterone and fasting blood glucose concentrations were not different between the two groups of PCOS women. Our data indicate that SDB and EDS are markedly and significantly more frequent in PCOS women than in premenopausal controls. Also, insulin resistance is a stronger risk factor than is body mass index or testosterone for SDB in PCOS women. These data support our proposal that, independently of gender, sleep apnea might be a manifestation of an endocrine/metabolic abnormality in which insulin resistance plays a principal role.     

Practice patterns of screening for sleep apnea in physicians treating PCOS patients

Women with polycystic ovarian syndrome (PCOS) have been shown to have a very high prevalence of obstructive sleep apnea (OSA). Screening for OSA is recommended for PCOS patients. How far this is carried out in actual practice is unknown. To study practice patterns with regard to screening for OSA in physicians—both obstetrician/gynecologists (ObGyn) and endocrinologist—who manage PCOS. A secondary aim of this study was to identify practice differences, if any. Two hundred ObGyn and 140 endocrine academic institutions were contacted and mailed with questionnaires, if willing to participate. Responses were obtained from 50 (29.4%) ObGyn physicians and 29 (26.4%) endocrine physicians. The questionnaire was closed-ended. Physicians reported a high occurrence of obesity—36.7% of the physicians reported that 75–100% of their patients had morbid obesity. However, reported prevalence of symptoms was low—86.1% of the physicians felt their patients snored infrequently (<25% of the time) and 74.7% felt that their patients had excess daytime sleepiness (EDS) infrequently. Of the physicians, 92.4% ordered a sleep study <25% of the time. No significant difference in practice between the specialties was identified. Physicians who manage PCOS patients do not believe that these patients have significant symptoms nor warrant frequent testing for OSA. This may reflect lack of knowledge about the link or may imply that PCOS patients remain largely asymptomatic. Educating specialist physicians managing PCOS about OSA and improved tools for OSA screening may improve detection.     

Metabolic disturbances in obesity versus sleep apnoea: the importance of visceral obesity and insulin resistance

Obstructive sleep apnoea (OSA) is a very prevalent disorder particularly amongst middle-aged, obese men, although its existence in women as well as in lean individuals is increasingly recognized. Despite the early recognition of the strong association between OSA and obesity, and OSA and cardiovascular problems, sleep apnoea has been treated as a 'local abnormality' of the respiratory track rather than as a 'systemic illness'. In 1997, we first reported that the pro-inflammatory cytokines interleukin (IL)-6 and tumour necrosis factor-alpha (TNF alpha) were elevated in patients with disorders of excessive daytime sleepiness (EDS) and proposed that these cytokines were mediators of daytime sleepiness. Also, we reported a positive correlation between IL-6 or TNF alpha plasma levels and the body mass index (BMI). In subsequent studies, we showed that IL-6, TNF alpha, leptin and insulin levels were elevated in sleep apnoea independently of obesity and that visceral fat, was the primary parameter linked with sleep apnoea. The association of OSA with insulin resistance and diabetes type 2 has been confirmed since then in several epidemiological and clinical studies. Furthermore, our findings that women with polycystic ovary syndrome (PCOS, a condition associated with hyperandrogenism and insulin resistance) were much more likely than controls to have sleep disordered breathing (SDB) and daytime sleepiness support the pathogenetic role of insulin resistance in OSA. Other findings that support the view that sleep apnoea and sleepiness may be manifestations of a serious metabolic disorder, namely the Metabolic or Visceral Obesity Syndrome, include: obesity without sleep apnoea is associated with daytime sleepiness; PCOS and diabetes type 2 are independently associated with EDS after controlling for SDB, obesity and age; and increased prevalence of sleep apnoea in postmenopausal women, with hormonal replacement therapy associated with a significantly reduced risk for OSA. In conclusion, accumulating evidence provides support to our model of the bi-directional, feedforward, pernicious association between sleep apnoea, sleepiness, inflammation and insulin resistance, all promoting atherosclerosis and cardiovascular disease.     

The sympathetic nervous system in polycystic ovary syndrome: a novel therapeutic target?

Polycystic ovary syndrome (PCOS) is a common endocrine condition associated with long‐term health risks, including type 2 diabetes and vascular dysfunction in addition to reproductive sequelae. Many of the common features of PCOS, such as central obesity, hyperinsulinaemia and obstructive sleep apnoea (OSA), are associated with chronic sympathetic overactivity, suggesting that sympathoexcitation may be involved in the pathogenesis of this condition. Rodent models of polycystic ovaries have shown that ovarian sympathetic outflow may be increased, accompanied by elevated intra‐ovarian synthesis of nerve growth factor (NGF) which may be involved in initiation of ovarian pathology. Patients with PCOS have evidence of increased muscle sympathetic nerve activity (MSNA), altered heart rate variability and attenuated heart rate recovery postexercise, compared with age‐ and BMI‐matched controls, suggesting a generalized increase in sympathetic nerve activity. Active weight loss can reduce MSNA and whole body noradrenaline spillover, whereas low‐frequency electroacupuncture decreased MSNA in overweight women with PCOS. Treatment of OSA with continuous positive airways pressure may reduce plasma noradrenaline levels and diastolic blood pressure and improve cardiac sympathovagal balance. Renal sympathetic denervation also reduced MSNA, noradrenaline spillover and blood pressure in two PCOS subjects with hypertension, accompanied by improved insulin sensitivity. The sympathetic nervous system may thus offer a new therapeutic target in PCOS but larger and longer‐term studies are needed before these treatments can be considered in clinical practice.     

Obstructive sleep apnea and excessive daytime sleepiness among patients with type 2 diabetes mellitus: a single-center study from Iran

Obstructive sleep apnea (OSA) and excessive daytime sleepiness (EDS) are common in patients with type 2 diabetes mellitus (T2DM). This study was aimed to evaluate the prevalence and risk factors of the OSA and EDS among Iranian patients with T2DM. We conducted a cross-sectional study on randomly selected 173 patients with T2DM aged 30 to 65. We assessed daytime sleepiness using the Epworth sleepiness scale and risk of OSA using the STOP-BANG questionnaire. Further information was demographic and anthropometric characteristics plus metabolic profile. Of all, 122 (74 %) patients were at high risk for OSA and 78 (45 %) patients suffered from EDS. Patients at high risk for OSA were older and had higher BMI, waist circumference, neck circumference, systolic, and diastolic blood pressure. In addition, men were significantly at a higher risk for OSA than women. Logistic regression revealed that age, male sex, and neck circumference were independent predictors of risk for OSA. The only independent predictor of EDS was age. Patients with T2DM are at high risk for OSA; also, daytime sleepiness is highly prevalent in this population. Our results indicated that the evaluation of OSA, EDS, and their risk factors should be included in the clinical management of patients with T2DM.     

Perioperative Versorgung von Patienten mit obstruktiver Schlafapnoe

Obstructive sleep apnea (OSA) is very common in patients who undergo orthopedic, general and cardiac surgery. Emerging evidence suggests that patients with known or suspected OSA are at increased risk for perioperative respiratory, cardiac and cerebral complications. The magnitude of the risk is linked to the severity of OSA and aggravating diseases (e.g. pulmonary disease and obesity) as well as to comorbidities that can be aggravated by OSA (e.g. coronary artery disease). This review discusses strategies for perioperative management, covering preoperative screening for and treatment of OSA, risk evaluation, modified premedication and anesthesia as well as postoperative monitoring of OSA patients. Management of ambulatory and in-patient surgery varies. Existing protocols of perioperative management of OSA patients are helpful and merit further systematic scientific validation.     

Obstructive Airway Disease and Obstructive Sleep Apnea: Effect of Pulmonary Function

This study sought to determine whether reduced pulmonary function in obstructive airway disease (OAD) is an independent risk factor for obstructive sleep apnea (OSA). This was a prospective observational study conducted at an outpatient pulmonary clinic. Adults with a known diagnosis of COPD/asthma were enrolled as OAD group. Family members without a history of COPD/asthma who accompanied these patients to the clinic were enrolled as a control group. The Berlin Questionnaire (BQ) was used to assess OSA risk in the OAD group and controls. Forced expiratory volume in 1 second (FEV(1) % predicted) was determined from spirometry. The subjects at high risk for OSA were referred for a full overnight polysomnogram (PSG). The prevalence of patients with a high risk of OSA was 55.2% in the OAD group, which was higher than in the controls (7.5%, p?相似文献   

The association of angiotensin-converting enzyme gene insertion/deletion polymorphisms with OSA: a meta-analysis

Obstructive sleep apnoea (OSA) is an independent risk factor for hypertension. Increased angiotensin-converting enzyme (ACE) activity may be a possible promoting mechanism with different ACE insertion/deletion (I/D) genotypes influencing this activity. Studies investigating the association of ACE I/D polymorphisms with OSA have shown conflicting results. We aimed to undertake a meta-analysis of existing studies exploring the association of ACE I/D polymorphisms with the risk of OSA and hypertension. 10 studies were included in a random effects meta-analysis, comprising 1,227 OSA subjects and 1,227 controls. The effect size was measured using the odds ratio. The risk of having OSA in carriers of the D allele was 0.92 (95% CI 0.69-1.23). There was statistically significant heterogeneity across the studies (I(2)=42%, p=0.08 and I(2)=74%, p<0.0001 for genotype and allele frequency, respectively). The association of D allele frequency with the risk of OSA remained nonsignificant after stratification based on ethnicity, source of population sample, and the presence of hypertension. Subgroup analysis failed to show any influence of genotype and allele frequency on OSA severity. This meta-analysis revealed no association between the ACE I/D polymorphisms and OSA susceptibility.     

Obstructive sleep apnoea and the risk of type 2 diabetes: A meta‐analysis of prospective cohort studies

Background and objective: There has been increasing recognition that obstructive sleep apnoea (OSA) is associated with incident type 2 diabetes. The aim of this study was to assess the association between the severity of OSA and the risk of type 2 diabetes by performing a meta‐analysis of all available prospective cohort studies. Methods: A search was conducted of the PubMed, EMBASE, CINAHL and ISI Web of Knowledge databases through March 2012 to identify studies linking OSA with the risk of diabetes. Only prospective cohort studies, in which the presence of OSA was confirmed by objective measurements, were included. Fixed and random effects models were used to calculate pooled relative risks (RR). Results: This meta‐analysis of six prospective cohort studies including a total of 5953 participants, with follow‐up periods of 2.7–16 years, and 332 incident cases of type 2 diabetes, showed that moderate‐severe OSA was associated with a greater risk of diabetes (RR 1.63; 95% confidence interval (CI): 1.09–2.45), as compared with the absence of OSA. Sensitivity analyses yielded similar results. For subjects with mild OSA, as compared with those without OSA, the pooled RR of developing type 2 diabetes was 1.22 (95% CI: 0.91–1.63). Conclusions: This meta‐analysis indicates that moderate‐severe OSA is associated with an increased risk of type 2 diabetes, and this appears to be an independent risk factor for the development of diabetes.     

The predictive value of Holter monitoring in the risk of obstructive sleep apnea

BackgroundPatients with obstructive sleep apnea (OSA) often present with cardiovascular symptoms. Holter monitors were reported to predict sleep apnea, though were rarely used in everyday clinical practice. In this study, by comparing Holter monitoring to polysomnography (PSG), we try to find out an operable way for clinicians to use Holter to predict OSA risk.MethodsPatients (n=63) suspected of OSA underwent Holter monitoring with concurrent PSG at a sleep center. Respiration and heart rate variability (HRV) indices were calculated from the Holter and compared with PSG indices.ResultsThe sensitivity of the Holter-derived respiratory waveform for OSA was 90.0%, and the specificity was 82.6%. The time domain indices including standard deviation of all NN intervals during 24 hours, mean of standard deviation of the averages of NN intervals in all 5-minute segments, square root of the mean squared differences of successive NN intervals, percentage of beat-to-beat NN interval differences that were more than 50 milliseconds, and the frequency domain index of high frequency decreased in participants with OSA and correlated with the PSG derived indices including apnea-hypopnea index (AHI), oxygen reduction index (ODI) and nadir SaO₂. Logistic regression showed that standard deviation of all NN intervals during 24 hours and gender could predict the risk of OSA (P<0.001), with a sensitivity for diagnosing moderate to severe OSA of 87.5% and could accurately distinguish the risk of OSA in 77.8% of patients. Males with standard deviation of all NN intervals during 24 hours ≤177 ms or females with standard deviation of all NN intervals during 24 hours ≤80.9 ms were considered to be at high risk for OSA.ConclusionsCommercial and common parameters from Holter monitoring could predict the risk of OSA with high sensitivity. Therefore, the risk of OSA may be assessed using the Holter examination to improve the diagnosis and treatment rate of OSA.     

Increased maternal pregnancy complications in polycystic ovary syndrome appear to be independent of obesity—A systematic review,meta‐analysis,and meta‐regression

Polycystic ovary syndrome (PCOS) is associated with an increased risk of maternal pregnancy and delivery complications. However, the impact of clinical features of PCOS and other potential risk factors in PCOS is still unknown. We aimed to investigate the association of PCOS with maternal pregnancy and delivery complications with consideration of risk factors and potential confounders. The meta‐analysis included 63 studies. PCOS was associated with higher miscarriage, gestational diabetes mellitus, gestational hypertension, pre‐eclampsia, induction of labour, and caesarean section. The association of PCOS with these outcomes varied by geographic continent, PCOS phenotypes, and study quality. Pre‐eclampsia and induction of labour were not associated with PCOS on body mass index‐matched studies. No outcome was associated with PCOS on assisted pregnancies. Age was significantly associated with higher miscarriage on meta‐regression. There were no studies assessing perinatal depression. We confirm that PCOS is associated with an increased risk of maternal pregnancy and delivery complications. The association of PCOS with the outcomes is worsened in hyperandrogenic PCOS phenotypes, in specific geographic continents, and in the highest quality studies but disappears in assisted pregnancies. Future studies in PCOS are warranted to investigate proper timing for screening and prevention of maternal pregnancy and delivery complications with consideration of clinical features of PCOS.     

Risk factors of polycystic ovarian syndrome among Li People

Objective: To study the relevant risk factors of polycystic ovarian syndrome(PCOS) of Li People so as to provide basis for early diagnosis and treatment of PCOS. Methods: With casecontrol study method, 285 cases of PCOS of Li People were as recruited case group, and 580 cases of non-PCOS of female Li People as control group. Questionnaire was adopted to collect data regarding risk factors of PCOS, then the risk factors of PCOS was searched by univariate and multivariate analysis. Results: Multivariate analysis showed that the risk factors of PCOS included in menstrual cycle disorder(OR=5.824), bad mood(OR=2.852), family history of diabetes(OR=7.008), family history of infertility(OR=11.953), menstrual irregularity of mother(OR=2.557) and lack of physical exercise(OR=1.866). Conclusions: To target the high risk factors of menstrual cycle disorder, family history of diabetes, family history of infertility, family history of diabetes, bad mood and lack of physical exercise of female population, we should implement early screen, diagnose and treatment of POCS in order to reduce the incidence rate of PCOS and improve prognosis of PCOS.     

Evidence for an association between metabolic cardiovascular syndrome and coronary and aortic calcification among women with polycystic ovary syndrome

Women with polycystic ovary syndrome (PCOS) exhibit an adverse cardiovascular risk profile, characteristic of the metabolic cardiovascular syndrome (MCS). The aim of this study was to determine the prevalence of coronary artery (CAC) and aortic (AC) calcification among middle-aged PCOS cases and controls and to explore the relationship among calcification, MCS, and other cardiovascular risk factors assessed 9 yr earlier. This was a prospective study of 61 PCOS cases and 85 similarly aged controls screened in 1993-1994 for risk factors and reevaluated in 2001-2002. The main outcome measures were CAC and AC, measured by electron beam tomography. Women with PCOS had a higher prevalence of CAC (45.9% vs. 30.6%) and AC (68.9% vs. 55.3%) than controls. After adjustment for age and body mass index, PCOS was a significant predictor of CAC (odds ratio = 2.31; P = 0.049). PCOS subjects were also 4.4 times more likely to meet the criteria for MCS than controls. High-density lipoprotein cholesterol and insulin appeared to mediate the PCOS influence on CAC. Interestingly, total testosterone was an independent risk factor for AC in all subjects after controlling for PCOS, age, and body mass index (P = 0.034). We conclude that women with PCOS are at increased risk of MCS and demonstrate increased CAC and AC compared with controls. Components of MCS mediate the association between PCOS and CAC, independently of obesity.     

Carotid Intima Media Thickness in Patients with Obstructive Sleep Apnea: Comparison with a Community-Based Cohort

Background

The impact of obstructive sleep apnea (OSA) on the development of atherosclerotic cardiovascular disease (CVD) in the absence of overt CVD or risk factors is unclear. Our purpose was to assess whether patients with OSA without overt CVD or risk factors have subclinical atherosclerosis as evaluated by carotid intima medial thickness (CIMT) compared to matched controls.

Methods

We measured CIMT in patients >40 years old, who underwent polysomnography for suspected OSA and did not have a history of CVD or risk factors (smoking, hypertension, diabetes, hyperlipidemia). OSA severity was classified according to apnea–hypopnea index. Serum levels of high-sensitivity C-reactive protein, fibrinogen, and lipids were assessed and relationships with OSA severity explored. CIMT measurements from patients with OSA were compared those of to age-, gender-, and BMI-matched controls from a community-based cohort without known CVD or OSA.

Results

Fifty-one patients were studied. Of these, patients with severe OSA had an increased CIMT compared to patients without OSA, but the relationship was not significant after controlling for age (p = 0.10). However, 37 patients had OSA and were matched to 105 controls. CIMT was significantly increased in OSA patients versus controls (0.77 vs. 0.68 mm, p = 0.03). The difference between patients and controls was greater for patients with severe OSA (0.83 vs. 0.71 mm) than for patients with mild-to-moderate OSA (0.71 vs. 0.67 mm).

Conclusions

Patients with OSA but without a history of or risk factors for CVD have increased CIMT compared to a BMI-, age-, and gender-matched cohort. This provides evidence that OSA is an independent risk factor for the development of CVD.     

Obesity and craniofacial structure as risk factors for obstructive sleep apnoea: impact of ethnicity

OSA is the result of structural and functional abnormalities that promote the repetitive collapse of the upper airway during sleep. This common disorder is estimated to occur in approximately 4% of men and 2% of women, with prevalence studies from North America, Australia, Europe and Asia indicating that occurrence is relatively similar across the globe. Anatomical factors, such as obesity and craniofacial morphology, are key determinants of the predisposition to airway collapse; however, their relative importance for OSA risk likely varies between ethnicities. Direct inter-ethnic studies comparing craniofacial phenotypes in OSA are limited. However, available data suggest that Asian OSA populations primarily display features of craniofacial skeletal restriction, African Americans display more obesity and enlarged upper airway soft tissues, while Caucasians show evidence of both bony and soft tissue abnormalities. Our recent comparison of Chinese and Caucasian OSA patients found for the same degree of OSA severity. Caucasians were more obese, and Chinese had more skeletal restriction. However, the ratio of obesity to craniofacial bony size (or anatomical balance, an important determinant of upper airway volume and OSA risk) was similar between Caucasians and Chinese OSA patients. Ethnicity appears to influence OSA craniofacial phenotype but furthermore the relative contribution of the anatomical factors underlying OSA risk. The skeletal restriction craniofacial phenotype may be particularly vulnerable to increasing obesity rates. Better understanding of craniofacial phenotypes encompassing ethnicity may help improve OSA recognition and treatment; however, further studies are needed to elucidate ethnic differences in OSA anatomical risk factors.     

Chronic liver injury during obstructive sleep apnea

Patients with obstructive sleep apnea (OSA) are at risk for the development of fatty liver as a result of being overweight. Several data suggest that OSA per se could be a risk factor of liver injury; ischemic hepatitis during OSA has been reported, and OSA is an independent risk factor for insulin resistance. Therefore, we investigated liver damage and potential mechanisms in 163 consecutive nondrinking patients with nocturnal polysomnographic recording for clinical suspicion of OSA. Serum levels of liver enzymes were measured in all patients. Liver biopsy was offered to patients with elevated liver enzymes. Intrahepatic hypoxia was assessed by the expression of vascular endothelial growth factor (VEGF) on liver biopsy specimens. Severe OSA (apnea-hypopnea index [AHI] > 50/hr) was seen in 27% of patients; 52% had moderate OSA (AHI 10-50/hr), and 21% had no OSA. Overall, 20% had elevated liver enzymes. Independent parameters associated with elevated liver enzymes were body mass index (BMI) (OR: 1.13; CI: 1.03-1.2) and severe OSA (OR: 5.9; CI: 1.2-29). Liver biopsy was performed in 18 of 32 patients with elevated liver enzymes and showed steatohepatitis in 12 cases, associated with fibrosis in 7 cases. Patients with severe OSA were more insulin-resistant according to homeostasis model assessment, had higher percentage of steatosis as well as scores of necrosis and fibrosis, despite similar BMI. Hepatic immunostaining used as an indirect marker of hypoxia was not different between patients with or without severe OSA. In conclusion, severe OSA is a risk factor for elevated liver enzymes and steatohepatitis independent of body weight. Promotion of insulin resistance is probably involved. Further studies are needed to determine whether hypoxia contributes directly to liver injury.