Dae Wui Yoon

Obstructive sleep apnea as a risk factor for cerebral white matter change in a middle-aged and older general population

STUDY OBJECTIVE Obstructive sleep apnea (OSA) contributes to the development of systemic hypertension, and hypertension strongly predicts the development of white matter change (WMC). Thus, it is plausible that OSA mediates WMC. The goal of the current study is to determine whether a contextual relationship exists between OSA and cerebral WMC. DESIGN Cross-sectional analyses conducted in a population-based study. SETTING Korean community-based sample from the Korean Genome and Epidemiology Study (KoGES) who attended examinations in 2011 at a medical center. PARTICIPANTS There were 503 individuals (mean ± SD, age 59.63 ± 7.48 y) who were free of previously diagnosed cardiovascular and neurologic diseases. MEASUREMENTS AND RESULTS Participants underwent 1-night polysomnography and were classified as no OSA (obstructive apnea-hypopnea index [AHI] < 5, n = 289), mild OSA (AHI 5-15, n = 161), and moderate to severe OSA (AHI ≥ 15, n = 53). WMC was identified with brain magnetic resonance imaging (MRI) and was found in 199 individuals (39.56%). Multivariate logistic regression analyses adjusted for covariates revealed that moderate to severe OSA was significantly associated with the presence of WMC (odds ratio [OR] 2.08, 95%, confidence interval [CI] 1.05-4.13) compared with no OSA. Additional adjustment of hypertension to the model did not alter the significance of the association (OR 2.03, 95% CI 1.02-4.05). CONCLUSIONS Moderate to severe OSA is an independent risk factor for WMC in middle-aged and older individuals. Thus, early recognition and treatment of OSA could reduce the risk of stroke and vascular dementia.

Inflammatory and transcriptional roles of poly (ADP-ribose) polymerase in ventilator-induced lung injury

IntroductionPoly (ADP-ribose) polymerase (PARP) participates in inflammation by cellular necrosis and the nuclear factor-kappa-B (NF-κB)-dependent transcription. The purpose of this study was to examine the roles of PARP in ventilator-induced lung injury (VILI) in normal mice lung.MethodsMale C57BL/6 mice were divided into four groups: sham tracheostomized (sham), lung-protective ventilation (LPV), VILI, and VILI with PARP inhibitor PJ34 pretreatment (PJ34+VILI) groups. Mechanical ventilation (MV) settings were peak inspiratory pressure (PIP) 15 cm H2O + positive end-expiratory pressure (PEEP) 3 cm H2O + 90 breaths per minute for the LPV group and PIP 40 cm H2O + PEEP 0 cm H2O + 90 breaths per minute for the VILI and PJ34+VILI groups. After 2 hours of MV, acute lung injury (ALI) score, wet-to-dry (W/D) weight ratio, PARP activity, and dynamic compliance (CD) were recorded. Tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), myeloperoxidase (MPO) activity, and nitrite/nitrate (NOX) in the bronchoalveolar lavage fluid and NF-κB DNA-binding activity in tissue homogenates were measured.ResultsThe VILI group showed higher ALI score, W/D weight ratio, MPO activity, NOX, and concentrations of TNF-α and IL-6 along with lower CD than the sham and LPV groups (P < 0.05). In the PJ34+VILI group, PJ34 pretreatment improved all histopathologic ALI, inflammatory profiles, and pulmonary dynamics (P < 0.05). NF-κB activity was increased in the VILI group as compared with the sham and LPV groups (P < 0.05) and was decreased in the PJ34+VILI group as compared with the VILI group (P = 0.009). Changes in all parameters were closely correlated with the PARP activity (P < 0.05).ConclusionOveractivation of PARP plays an important role in the inflammatory and transcriptional pathogenesis of VILI, and PARP inhibition has potentially beneficial effects on the prevention and treatment of VILI.

Association of Obstructive Sleep Apnea and Glucose Metabolism in Subjects With or Without Obesity

OBJECTIVE The purpose of this study was to investigate whether the impact of obstructive sleep apnea (OSA) on glucose metabolism was different according to the presence or absence of obesity. RESEARCH DESIGN AND METHODS A total of 1,344 subjects >40 years old from the Korean Genome and Epidemiology Study were included. OSA was detected by home portable sleep monitoring. Plasma glucose, HbA1c, and insulin resistance were compared according to OSA and obesity status. The associations between OSA and impaired fasting glucose (IFG), impaired glucose tolerance (IGT), IFG + IGT, and diabetes were evaluated in subjects with and without obesity after adjusting for several confounding variables. The effect of visceral obesity on this association was evaluated in 820 subjects who underwent abdominal computed tomography scanning. RESULTS In subjects without obesity, fasting glucose, 2-h glucose after 75-g glucose loading, and HbA1c were higher in those with OSA than in those without after controlling for age, sex, and BMI. In addition, the presence of OSA in nonobese subjects was associated with a higher prevalence of IFG + IGT and diabetes after adjusting for several confounding variables (odds ratio 3.15 [95% CI 1.44–6.90] and 2.24 [1.43–3.50] for IFG + IGT and diabetes, respectively). Further adjustment for visceral fat area did not modify this association. In contrast, in those with obesity, none of the abnormal glucose tolerance categories were associated with OSA. CONCLUSIONS The presence of OSA in nonobese individuals is significantly associated with impaired glucose metabolism, which can be responsible for future risk for diabetes and cardiovascular disease.

Tae-Eum Type as an Independent Risk Factor for Obstructive Sleep Apnea

Obstructive sleep apnea (OSA) is prevalent and associated with several kinds of chronic diseases. There has been evidence that a specific type of Sasang constitution is a risk factor for metabolic and cardiovascular diseases that can be found in patients with OSA, but there are no studies that address the association between the Sasang constitution type (SCT) and OSA. The purpose of this study was to investigate the association between the SCT and OSA. A total of 652 participants were included. All participants were examined for demographic information, medical history, and completed an interviewer-administered questionnaire on life style and sleep-related variables. Biochemical analyses were performed to determine the glucose and lipid profiles. An objective recording of OSA was done with an unattended home PSG using an Embla portable device. The apnea-hypopnea index (AHI) and oxygen desaturation index (ODI) were significantly higher in the Tae-eum (TE) type as compared to the So-eum (SE) and the So-yang (SY) types. Even after adjusting for confounding variables, the TE type still had a 2.34-fold (95% CI, 1.11–4.94; P = 0.0262) increased risk for OSA. This population-based cohort study found that the TE constitutional type is an independent risk factor for the development of OSA.

So-Eum Type as an Independent Risk Factor for Irritable Bowel Syndrome: A Population-Based Study in Korea

OBJECTIVES It has been hypothesized that Sasang constitutional types (SCTs) have a specific hypoactive organ, which can account for vulnerability to related diseases or symptoms. This study examined the relationship between SCTs and irritable bowel syndrome (IBS). DESIGN Cross-sectional study in a population-based cohort study in Korea. PARTICIPANTS 1362 individuals (705 men and 657 women) who participated in the Korean Genome and Epidemiology Study. OUTCOME MEASURES The participants were classified into SCTs by the integrated diagnostic model and asked about symptoms related to IBS using the Rome II criteria. RESULTS The prevalence of IBS differed significantly among the SCTs, with 33 (18.3%) of the So-eum (SE) type, 74 (9.9%) of the Tae-eum (TE) type, and 57 (13.2%) of the So-yang (SY) type having IBS. Even after adjustment for possible confounders, the SE type for both sexes continued to show 1.82-fold (95% confidence interval [CI], 1.05-3.16) excess odds of having IBS. Men with SE type had a 2.97 times (95% CI, 1.34-6.58) and a 2.50 times (95% CI, 1.15-5.47) significantly higher odds of having IBS than the TE and SY types, respectively. In analysis for the joint effect of SCT and psychological stress, the multivariate odds ratio of IBS was 3.21 (95% CI, 1.33-7.75) for the SE type and Psychological Well-Being Index-Short Form (PWI-SF) score (<27), and 5.83 (95% CI, 1.80-18.88) for the SE type and PWI-SF (≥27) compared with the TE type and PWI-SF score (<27). CONCLUSIONS The SE type of SCT is an independent risk factor for IBS. The findings support the hypothesis that persons with SE type are vulnerable to gastrointestinal diseases.

Concurrent presence of inflammation and obstructive sleep apnea exacerbates the risk of metabolic syndrome: A KoGES 6-year follow-up study

Abstract 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 (&Dgr;BMI) 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.

Association between high nocturnal blood pressure and white matter change and its interaction by obstructive sleep apnoea among normotensive adults

Objectives: A reverse dipping pattern, characterized by higher night-time blood pressure (BP) than daytime BP, is associated with the increased risk for cerebrovascular disease, cardiovascular events and all-cause mortality. However, little has known about the association between white matter change (WMC) and reverse dipping pattern, particularly in normotensive adults. We aimed to examine whether WMC is associated with BP dipping patterns as measured with a 24-h ambulatory BP monitoring and whether obstructive sleep apnoea (OSA) is involved in this relationship Methods: A total of 703 normotensive adults were from an ongoing longitudinal study in a general population. WMC was measured with brain MRI. BP dipping patterns were defined as the ratio of the change in night-time and daytime SBP. OSA was categorized with the apnoea-hypopnea index, as measured with polysomnography. To avoid the influence of hypertensive medications, we only included normotensive adults for the final analysis. To examine the associations between WMC and dipping patterns, we built logistic models. To elucidate the role of OSA, we also conducted both modification and mediation tests. Results: Reverse dipping pattern was significantly associated with WMC (odds ratio 1.49, 95% confidence interval 1.02–2.18). Further, OSA modified the association between dipping patterns and WMC (P = 0.0118). No mediation effect of OSA was assessed. Conclusion: In 703 normotensive adults, the reverse dipping pattern showed a significant association with WMC, after adjusting for covariates. Further, according to the presence of OSA, the association between reverse dipping and WMC was varied.

Obstructive sleep apnea is associated with elevated high sensitivity C-reactive protein levels independent of obesity: Korean genome and epidemiology study

Obstructive sleep apnea syndrome (OSA) has been recognized as a common health problem, and increasing obesity rates have led to further remarkable increases in the prevalence of OSA, along with more prominent cardiovascular morbidities. Though previous studies have reported an independent relationship between elevated high sensitivity C-reactive protein (hsCRP) levels and OSA, the issue remains controversial owing to inadequate consideration of obesity and various confounding factors. So far, few population based studies of association between OSA and hsCRP levels have been published. Therefore, the purpose of the present study was to investigate whether OSA is associated with increased hsCRP levels independent of obesity in a large population-based study. A total of 1,835 subjects (968 men and 867 women) were selected from a larger cohort of the ongoing Korean Genome and Epidemiology Study (KoGES). Overnight polysomnography was performed on each participant. All participants underwent anthropometric measurements and biochemical analyses, including analysis of lipid profiles and hsCRP levels. Based on anthropometric data, body mass index (BMI) and waist hip ratio (WHR) were calculated and fat mass (FM) were measured by means of multi-frequency bioelectrical impedance analysis (BIA). Mild OSA and moderate to severe OSA were defined by an AHI >5 and ≥15, respectively. The population was sub-divided into 3 groups based on the tertile cut-points for the distribution of hsCRP levels. The percentage of participants in the highest tertile of hsCRP increased dose-dependently according to the severity of OSA. After adjustment for potential confounders and obesity-related variables (BMI, WHR, and body fat) in a multiple logistic model, participants with moderate to severe OSA had 1.73-, 2.01-, and 1.61-fold greater risks of being in the highest tertile of hsCRP levels than participants with non-OSA, respectively. Interaction between obesity (BMI ≥25kg/m2) and the presence of moderate-to-severe OSA was significant on the middle tertile levels of hsCRP (OR = 2.4), but not on the highest tertile, compared to the lowest tertile. OSA is independently associated with elevated hsCRP levels and may reflect an increased risk for cardiovascular morbidity. However, we found that OSA and obesity interactively contribute to individuals with general levels of hsCRP (<1.01 mg/dl). The short-term and long-term effects of elevated hsCRP levels on cardiovascular risk in the context of OSA remain to be defined in future studies.

The association between irritable bowel syndrome and the coexistence of depression and insomnia

OBJECTIVE The individual occurrence of depression or insomnia is a risk factor for irritable bowel syndrome (IBS), but few researchers have evaluated the association between comorbid depression and insomnia and IBS. The aim of the present study is to explore the relationship between IBS and the coexistence of depression and insomnia in a Korean population-based cohort study. METHODS A total of 3429 individuals who were enrolled in the Korean Genome and Epidemiology Study were analysed. Of the participants, 10.9% (n=374) were diagnosed with IBS based on the Rome II criteria. Regarding depressive symptoms, subjects were sub-divided into three groups based on the Beck Depression Inventory (BDI) score. Insomnia was defined as a positive response to at least one of three questions on sleep states. RESULTS The odds ratio (OR) of IBS increased proportionally as depressive symptoms worsened (OR: 1.64; 95% CI: 1.21-2.23 in middle tertile and OR: 2.61; 95% CI: 1.92-3.55 in highest tertile). Subjects with insomnia showed a higher OR of IBS than those without insomnia (OR: 1.81; 95% CI: 1.44-2.27). In the joint analysis of BDI and insomnia, the odds for IBS were significantly higher in all BDI tertiles with insomnia than in the corresponding BDI tertiles without insomnia. There was no significant interaction effect of BDI tertile and insomnia on IBS. CONCLUSION The presence of both depression and insomnia is significantly associated with IBS compared to each individual occurrence. Further prospective investigations are needed to explore possible causality between comorbid depression and insomnia and IBS.

Association of Sasang Constitutional Types with Incident Hypertension: A 12-Year Follow-Up Study

OBJECTIVES Sasang constitutional types (SCTs) are four distinct classifications of people based on physiologic and physical characteristics. The different types have been reported to have different disease susceptibility, but there are no studies reporting the association of SCT and hypertension (HTN) over a long-term follow-up period. This study prospectively investigated the association between SCT and incidence of HTN. DESIGN This was a prospective study in a population-based cohort study in Korea. SUBJECTS Data from two independent population-based cohorts that are embedded within the Korean Genome and Epidemiology Study were used. A total of 2083 subjects who were free of HTN at baseline were selected for the analysis. OUTCOME MEASURES HTN was diagnosed as systolic blood pressure (BP) ≥140 mmHg and diastolic BP ≥90 mmHg, use of antihypertensive medication, or diagnosis by doctor. The SCTs were classified using an integrated diagnostic method that included facial features, body shape, voice, and questionnaire responses. The association between the SCT and the incidence of HTN was investigated by Cox proportional hazard regression analysis and calculation of estimated survival functions. RESULTS The Tae-eum (TE) type showed a significantly increased risk for HTN (hazard ratio [HR] = 1.55, 95% confidence interval [CI] 1.15-2.10; p = 0.005), even after adjusting for all possible confounders. In a stratified analysis by body mass index (BMI) conducted only in the TE type, even those in the TE type with normal BMI had a significantly higher risk for HTN (HR = 1.47, 95% CI 1.07-2.03; p = 0.016). Furthermore, survival analysis showed that the TE type had a higher rate of developing HTN than the So-eum and So-yang types had, regardless of obesity status. CONCLUSIONS These results show that the TE type is an independent risk factor for HTN. Thus, early prevention and treatment for HTN in this type are needed.