Aibek E. Mirrakhimov

Prevalence of obstructive sleep apnea in Asian adults: a systematic review of the literature

BackgroundObstructive sleep apnea (OSA) is a common disease, affecting approximately 2% of women and 4% of men residing in Western communities. No systematically reviewed data are available about the prevalence of this disease in Asia, the most heavily populated continent.MethodsPubMed/Medline, Scopus and Google Scholar were searched for articles published from 1993 to May 2012 that reported the prevalence of OSA diagnosed via sleep monitoring and the prevalence of patients at risk for OSA as assessed by symptomatology and/or sleep questionnaires. We have also searched abstract database of major pulmonary and sleep scientific societies for relevant abstracts presented from 2010 to 2012. The following inclusion criteria were used: articles published in English, age ≥ 18 years, ≥ 100 participants in studies using sleep monitoring for the diagnosis of OSA, ≥ 300 participants in studies using questionnaires to detect patients at high risk for OSA. Exclusion criteria: duplicate publications, studies reporting the prevalence of central sleep apnea only, hospital based studies as well as studies assessing OSA prevalence among patients with resistant arterial hypertension, chronic kidney disease, heart failure and in patients with concomitant neurological disease.ResultsTwenty four articles were found to meet the inclusion criteria, covering 47,957 subjects (26,042 men and 21,915 women) and four relevant abstracts were noted. OSA prevalence ranged from 3.7% to 97.3%. Male gender, older age, a higher BMI and waist to hip ratio, greater neck circumference, arterial hypertension, smoking, snoring and daytime sleepiness were associated with OSA. Sample size, difference between the populations studied and the fact that some works included patients with a high pre-test probability of OSA explain the difference in prevalence rates.ConclusionThis systematic review highlights the lack of data regarding the prevalence of OSA in Asians. Only a few studies provide an approximate estimate of the OSA burden in some Asian communities.

Chronic obstructive pulmonary disease and glucose metabolism: a bitter sweet symphony

Chronic obstructive pulmonary disease, metabolic syndrome and diabetes mellitus are common and underdiagnosed medical conditions. It was predicted that chronic obstructive pulmonary disease will be the third leading cause of death worldwide by 2020. The healthcare burden of this disease is even greater if we consider the significant impact of chronic obstructive pulmonary disease on the cardiovascular morbidity and mortality.Chronic obstructive pulmonary disease may be considered as a novel risk factor for new onset type 2 diabetes mellitus via multiple pathophysiological alterations such as: inflammation and oxidative stress, insulin resistance, weight gain and alterations in metabolism of adipokines.On the other hand, diabetes may act as an independent factor, negatively affecting pulmonary structure and function. Diabetes is associated with an increased risk of pulmonary infections, disease exacerbations and worsened COPD outcomes. On the top of that, coexistent OSA may increase the risk for type 2 DM in some individuals.The current scientific data necessitate a greater outlook on chronic obstructive pulmonary disease and chronic obstructive pulmonary disease may be viewed as a risk factor for the new onset type 2 diabetes mellitus. Conversely, both types of diabetes mellitus should be viewed as strong contributing factors for the development of obstructive lung disease. Such approach can potentially improve the outcomes and medical control for both conditions, and, thus, decrease the healthcare burden of these major medical problems.

Obstructive Sleep Apnea and Non-Alcoholic Fatty Liver Disease: Is the Liver Another Target?

Obstructive sleep apnea (OSA) is recurrent obstruction of the upper airway during sleep leading to intermittent hypoxia (IH). OSA has been associated with all components of the metabolic syndrome as well as with non-alcoholic fatty liver disease (NAFLD). NAFLD is a common condition ranging in severity from uncomplicated hepatic steatosis to steatohepatitis (NASH), liver fibrosis, and cirrhosis. The gold standard for the diagnosis and staging of NAFLD is liver biopsy. Obesity and insulin resistance lead to liver steatosis, but the causes of the progression to NASH are not known. Emerging evidence suggests that OSA may play a role in the progression of hepatic steatosis and the development of NASH. Several cross-sectional studies showed that the severity of IH in patients with OSA predicted the severity of NAFLD on liver biopsy. However, neither prospective nor interventional studies with continuous positive airway pressure treatment have been performed. Studies in a mouse model showed that IH causes triglyceride accumulation in the liver and liver injury as well as hepatic inflammation. The mouse model provided insight in the pathogenesis of liver injury showing that (1) IH accelerates the progression of hepatic steatosis by inducing adipose tissue lipolysis and increasing free fatty acids (FFA) flux into the liver; (2) IH up-regulates lipid biosynthetic pathways in the liver; (3) IH induces oxidative stress in the liver; (4) IH up-regulates hypoxia inducible factor 1 alpha and possibly HIF-2 alpha, which may increase hepatic steatosis and induce liver inflammation and fibrosis. However, the role of FFA and different transcription factors in the pathogenesis of IH-induced NAFLD is yet to be established. Thus, multiple lines of evidence suggest that IH of OSA may contribute to the progression of NAFLD but definitive clinical studies and experiments in the mouse model have yet to be done.

Obstructive sleep apnea and kidney disease: is there any direct link?

BackgroundObstructive sleep apnea (OSA) is a common and underrecognized disorder affecting at least 2% and 4% of women and men, respectively. Chronic kidney disease (CKD), on the other hand, affects around 13% of US adults. Both of these conditions share some risk factors such as age, obesity, and smoking and are associated with increased cardiovascular morbidity and mortality. By itself OSA may play a role in the development of arterial hypertension, metabolic syndrome, type 2 diabetes mellitus, and dyslipidemia with potential impact on CKD development and/or progression. But the data regarding OSA and CKD are relatively scant.DiscussionMoreover, several studies had shown possible harmful effects on kidney function independent from conventional risk factors. CKD is associated with excessive fluid volume, with potential shift during recumbency towards the neck area with increased upper airway resistance. Thus, OSA and CKD may be the results of each other and when present together may impose much greater cardiovascular risk than either disease alone.

An association between TRP64ARG polymorphism of the B3 adrenoreceptor gene and some metabolic disturbances.

BackgroundsB3 adrenoreceptors (ADRB3) are abundant in adipose tissue and play the role in its metabolism and lipolysis. Some variants of the ADRB3 gene may predispose subjects for the development obesity and metabolic abnormalities in the setting of modern sedentary lifestyle. ADRB3 gene polymorphism association with metabolic disturbances has never been studied before in the ethnic Kyrgyz population.AimTo study an association between Trp64Arg polymorphism of the ADRB3 and metabolic syndrome (MS) components in an ethnic Kyrgyz group.Materials and methods213 Ethnic Kyrgyz volunteers over the age of 30 were enrolled in the study. The assessment plan for each individual comprised of general physical and anthropometric exams as well as laboratory tests (glucose, lipid panel, insulin) and genotyping by Trp64Arg polymorphism of the ADRB3. MS diagnosis was consistent with modified ATP III criteria (2005). Logistic regression analysis was performed to test the potential independent association between Arg64 allele with obesity, abdominal obesity (AO) and arterial hypertension (AH).ResultsTrp64Arg polymorphism of the ADRB3 was assessed in 213 individuals (145 men, 68 women) aged 30-73 (mean age 50.7 ± 7.6). Arg64 allele frequency was 0.239; ADRB3 genotype distribution among participants was: Trp64 homozygotes 54.5%, Trp64Arg 43.2% and Arg64 homozygotes 2.3%. There was an association between Trp64Arg и Arg64Arg genotypes and higher BMI, WC and obesity frequency (p < 0.00009), AO (p < 0.01), type 2 diabetes mellitus (DM) (p < 0.005) and lower high density cholesterol (HDL-C) level (p < 0.03). The logistic regression analysis showed the correlation of the Arg64 allele with obesity (OR 3.159; 95% CI 1.789-5.577) and AO (OR 1.973; 95% CI 1.118-3.481). The association between Arg64 allele and AH lost its significance after adjustment for obesity.ConclusionArg64 allele of the ADRB3 gene in the studied group has an association with MS components such as obesity, AO and decreased HDL-C level.

Cut off values for abdominal obesity as a criterion of metabolic syndrome in an ethnic Kyrgyz population (Central Asian region).

BackgroundPeople of different racial and ethnic backgrounds have a distinct pattern of central fat deposition, thus making it necessary to devise a race based approach for the diagnosis and evaluation of abdominal obesity (AO). This is the first study to determine the optimal waist circumference (WC) cutoff values for definition of AO in an ethnic Kyrgyz population.Methods323 persons of Kyrgyz ethnicity (183 women and 140 men), with a mean age of 51.8 ± 9.5 years old were included in the study. Measurement of blood pressure (BP), anthropometric data (including body mass index calculation and WC measurement), fasting blood sugar, serum lipid parameters and insulin were performed in all examined individuals. Insulin resistance (IR) was considered as HOMA index (insulin × fasting glucose/22.5) ≥ 2.77. Sensitivity and specificity for the presence of IR or two other criteria of MS (according to the international classification, 2009) were calculated by using receiver operating characteristic (ROC) curves for men and women separately.ResultsThe optimal sensitivity and specificity obtained from the ROC curves for IR were 88 cm in women (sensitivity of 0.85, 95%CI (0.72-0.93), specificity of 0.58, 95%CI (0.49-0.66)) and 94 cm for men (sensitivity of 0.8, 95% CI (0.65-0.91), specificity of 0.61, 95% CI (0.51-0.71)). The data from the ROC curve for any two other MS criteria confirmed the results and the WC 88 cm in women (sensitivity of 0.82, 95% CI (0.72-0.9), specificity of 0.72, 95% CI (0.62-0.8)) and 94 cm in men (sensitivity of 0.74, 95% CI (0.62-0.84), specificity of 0.73, 95% CI (0.61-0.83)) were corresponded to the optimal sensitivity and specificity.ConclusionWC ≥ 88 cm and ≥ 94 cm should be used as a criterion for the diagnosis of AO for Kyrgyz women and men respectively based on these results.

Physical exercise related improvement in obstructive sleep apnea. Look for the rostral fluid shift

Obstructive sleep apnea (OSA) is a common and underdiagnosed medical disorder. OSA is associated with the symptoms of excessive daytime sleepiness (EDS). These patients typically follow a sedentary lifestyle, and sedentary behavior is related to impaired fluid dynamics in the lower body, particularly the legs. In a supine position this fluid can move towards the neck, with a subsequent increase in upper airway (UA) resistance and UA collapse. Several studies have shown that rostral fluid shift worsens OSA; however, whether physical activity can influence this has not been tested. Physical activity related improvement in OSA severity cannot be fully explained by a weight loss in the performed studies, which is of particular importance. One of the potential additional pathways is via an improvement in leg fluid dynamics, with a subsequent decrease in the supine fluid shift toward the neck, since physical activity improves leg fluid dynamics. It is likely that patients with fluid overload states such as heart failure, chronic kidney disease and resistant arterial hypertension, as well as patients with EDS are likely to benefit the most from physical exercise in terms of better leg fluid clearance, and potentially in terms of OSA severity. However, none of the studies have directly assessed the potential effect of physical activity on the leg fluid volume, and more importantly on the supine fluid shift and OSA severity. These questions should be addressed in future studies of the effects of physical exercise on OSA severity.

Nonalcoholic fatty pancreatic disease and cardio-metabolic risk: is there is a place for obstructive sleep apnea?

BackgroundObstructive sleep apnea is a common disorder acting as a risk factor for the development and progression of cardiometabolic derangements including non-alcoholic fatty liver disease. Recent research data suggest that non-alcoholic fatty pancreatic disease may be a more sensitive marker than non-alcoholic fatty liver disease for early subclinical metabolic risk and may contribute to the progression of subclinical disease to overt type 2 diabetes mellitus.Presentation of the hypothesisWe postulate that obstructive sleep apnea may be a risk factor for non-alcoholic fatty pancreatic disease. It is well known that intermittent hypoxia related to obstructive sleep apnea leads to hormonal derangements. Excessive lipolysis, enhanced lipid synthesis and systemic and local inflammation may favor ectopic fat deposition similarly to non-alcoholic fatty liver disease. Furthermore, it is possible that obstructive sleep apnea can lead to pancreatic beta cell damage via intermittent hypoxia.Testing of the hypothesisFuture research should focus on the following: first, whether non-alcoholic fatty pancreatic disease is an independent risk factor for the development of metabolic disease including diabetes mellitus or is a simple consequence of obesity; second, the prevalence of non-alcoholic fatty pancreatic disease among people with obstructive sleep apnea and vice versa, which should be compared to the prevalence of these diseases in general population; third, whether coexistence of these conditions is related to greater cardiometabolic risk than either disease alone; and fourth, whether the treatment of obstructive sleep apnea will translate into the resolution of non-alcoholic fatty pancreatic disease.Implications of the hypothesisIf proven, this hypothesis will provide new knowledge on the complex interplay between various metabolic insults. Second, screening for NAFPD may identify individuals at risk for developing type 2 diabetes mellitus for targeted prevention. Third, screening for the presence of non-alcoholic fatty pancreatic disease in patients with obstructive sleep apnea may help to decrease the incidence of diabetes mellitus through a targeted prevention.

Sleep apnoea and post-stroke vascular events: is it only due to poor continuous positive airway pressure use?

Introduction: Asthma control test as many other validated questionnaires are used to assess level of control. However, they do not identify factors that may lead to poor control such as medication compliance and inhaler technique. In this study level of asthma control was assessed by using asthma control test (ACT) and simultaneously the accuracy of compliance with preventer medications and inhaler technique were evaluated. The main objective of the study is to find out the relationship between compliance and inhaler technique with the level of asthma control. Methodology: Prospective 3 months study (1st February – 31st May 2011) was conducted in a university hospital in Oman. Asthmatic adult patients on preventer inhaled medications were included. ACT was used to assess level of asthma control. Inhaler technique was evaluated using a standardized checklist. Compliance was assessed using a pre designed scoring system. Results : 218 patients were assessed. Poor control was found in126 (58%) patients, of whom 74 (59%) had poor compliance and 34(27%) had poor inhaler technique. There was no significant difference in the level of control between patients with good and partial compliance (60% vs 59%). Only 35 (16%) patients had good level of control and good compliance and good inhaler technique. Conclusion: Since compliance and inhaler technique have a direct effect on the level of control, they should be part of all asthma assessment tools.

Comment on: Obstructive sleep apnoea in relation to rheumatic disease

Andrew Lim, David Speers and Charles Inderjeeth Rheumatology Department, Sir Charles Gairdner Hospital, University of Western Australia, Medicine and Pharmacology, Perth and PathWest Laboratory Medicine, Department of Microbiology, Nedlands, Western Australia. Accepted 2 October 2012 Correspondence to: Charles Inderjeeth, Rheumatology Department, Sir Charles Gairdner Hospital, Hospital Avenue, Nedlands, Perth, Western Australia 6009. E-mail: charles.inderjeeth@health.wa.gov.au