Association of coronary artery calcification with obstructive sleep apnea and obesity in middle-aged men

Background and aimsObstructive sleep apnea (OSA) and obesity are closely associated, and both have been reported to increase the risk of coronary heart disease. Although obesity is known to be associated with coronary artery calcification (CAC), there is limited information on whether OSA is associated with CAC independent of obesity.Methods and resultsA cross-sectional study examined the association between OSA and CAC among 258 healthy men, ages 40–49 years old, randomly selected from a population-based cohort. All individuals underwent overnight polysomnography and electron-beam computed tomography to measure their apnea–hypopnea index (AHI) and degree of CAC. A logistic regression model including potential cardiovascular risk factors excluding body mass index (BMI) showed that the presence of CAC was significantly greater in the fourth quartile versus the first quartile of AHI severity (odds ratio [OR] 2.21, 95% confidence interval [CI] 1.01–4.86). A multivariate linear regression model excluding BMI also showed that AHI was significantly associated with CAC (P = 0.004). However, this association was no longer significant after adjusting for BMI.ConclusionsIn our cross-sectional study, even though both OSA and obesity were positively associated with the presence and extent of CAC, only obesity remained a significant independent contributor after an adjustment for potential cardiovascular risk factors, irrespective of OSA.     

Endothelial dysfunction and inflammatory reactions of elderly and middle-aged men with obstructive sleep apnea syndrome

Introduction  Obstructive sleep apnea syndrome (OSAS) is considered to be associated with cardiovascular complications, and atherosclerosis could mediate this relationship. Cardiovascular risk factors of OSAS still need to be elucidated in elderly patients, since studies about the association between OSAS and cardiovascular diseases have been done mainly in middle-aged adults. To investigate whether endothelial dysfunction, as an early marker of atherosclerosis, and inflammatory responses in OSAS were affected by age, we studied flow-mediated dilatation (FMD) and C-reactive protein (CRP) in elderly and middle-aged patients with OSAS. Materials and methods  This study enrolled 161 male subjects of 117 middle-aged (35–59 years old) and 44 elderly (≥60 years old) patients with OSAS. After they finished nocturnal polysomnography (NPSG), FMD was measured on the brachial artery and blood samples were obtained to determine serum CRP levels. Results and discussion  FMD was significantly lower in the elderly patients (p = 0.04), but no difference was observed between two age groups in body mass index (BMI), neck circumference, waist-to-hip ratio, apnea hypopnea index (AHI), serum CRP level, or NPSG findings related with nocturnal hypoxemia such as average O₂ saturation, percentage of time below 90% O₂ saturation, and oxygen desaturation index (ODI). From the results of stepwise multiple linear regression analysis, the lowest oxygen saturation was a significant determinant of FMD (β = 0.25, p < 0.01, adjusted R ² = 6%), and BMI (β = 0.22, p < 0.05) and waist-to-hip ratio (β = 0.21, p < 0.05) were significant variables to explain CRP (adjusted R ² = 11%, p < 0.01) in the middle aged patients. In the elderly patients, no variable was significant for predicting FMD, but AHI was significant determinant of CRP (β = 0.46, p < 0.01, adjusted R ² = 19%, p < 0.01). In predicting cardiovascular risks of OSAS, both hypoxia and obesity should be considered in the middle-aged group, whereas nocturnal respiratory disturbances are important in the elderly group.     

Decreased pituitary-gonadal secretion in men with obstructive sleep apnea

Decreased libido is frequently reported in male patients with obstructive sleep apnea (OSA). The decline in morning serum testosterone levels previously reported in these patients was within the normal adult male range and does not explain the frequent association of OSA and sexual dysfunction. We determined serum LH and testosterone levels every 20 min between 2200-0700 h with simultaneous sleep recordings in 10 men with sleep apnea and in 5 normal men free of any breathing disorder in sleep. The mean levels and area under the curve of LH and testosterone were significantly lower in OSA patients compared with controls [LH, 24.9 +/- 10.2 IU/liter.h vs. 43.4 +/- 9.5 (P < 0.005); testosterone, 67.2 +/- 11.5 nmol/liter.h vs. 113.3 +/- 26.8 (P < 0.003)]. Four of 10 patients had hypogonadal morning (0700 h) serum testosterone levels. Analysis of covariance (ANCOVA) revealed that the 2 groups differed significantly in the amount of LH and testosterone secreted at night independent of age or degree of obesity. After partialing out body mass index, there was a significant negative correlation between the amounts of LH and testosterone secreted at night and the respiratory distress index, but not with degree of hypoxia. Our findings suggest that OSA in men is associated with dysfunction of the pituitary-gonadal axis. The relation between LH-testosterone profiles and the severity of OSA suggests that sleep fragmentation and, to a lesser extent, hypoxia in addition to the degree of obesity and aging may be responsible for the central suppression of testosterone in these patients.     

Increased incidence of cardiovascular disease in middle-aged men with obstructive sleep apnea: a 7-year follow-up

The incidence of a cardiovascular disease (CVD) was explored in a consecutive sleep clinic cohort of 182 middle-aged men (mean age, 46.8 +/- 9.3; range, 30-69 years in 1991) with or without obstructive sleep apnea (OSA). All subjects were free of hypertension or other CVD, pulmonary disease, diabetes mellitus, psychiatric disorder, alcohol dependency, as well as malignancy at baseline. Data were collected via the Swedish Hospital Discharge Register covering a 7-year period before December 31, 1998, as well as questionnaires. Effectiveness of OSA treatment initiated during the period as well as age, body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP) at baseline, and smoking habits were controlled. The incidence of at least one CVD was observed in 22 of 60 (36.7%) cases with OSA (overnight oxygen desaturations of 30 or more) compared with in 8 of 122 (6.6%) subjects without OSA (p < 0.001). In a multiple logistic regression model, significant predictors of CVD incidence were OSA at baseline (odds ratio [OR] 4.9; 95% confidence interval [CI], 1.8-13.6) and age (OR 23.4; 95% CI, 2.7-197.5) after adjustment for BMI, SBP, and DBP at baseline. In the OSA group, CVD incidence was observed in 21 of 37 (56.8%) incompletely treated cases compared with in 1 of 15 (6.7%) efficiently treated subjects (p < 0.001). In a multiple regression analysis, efficient treatment was associated with a significant risk reduction for CVD incidence (OR 0.1; 95% CI, 0.0-0.7) after adjustment for age and SBP at baseline in the OSA subjects. We conclude that the risk of developing CVD is increased in middle-aged OSA subjects independently of age, BMI, SBP, DBP, and smoking. Furthermore, efficient treatment of OSA reduces the excess CVD risk and may be considered also in relatively mild OSA without regard to daytime sleepiness.     

Compliance with CPAP therapy in older men with obstructive sleep apnea

OBJECTIVES: Factors specifically affecting compliance with continuous positive airway pressure (CPAP) in older patients with obstructive sleep apnea (OSA) have not been described. The purpose of this study is to determine which factors are associated with compliance and noncompliance in older patients, a growing segment of the population. DESIGN: A retrospective chart review of older male patients prescribed CPAP therapy for OSA over an 8-year period. SETTING: Veterans Affairs Medical Center. PARTICIPANTS: All patients age 65 and older for whom CPAP therapy had been prescribed for treatment of OSA in the past 8 years. MEASUREMENTS: Records of all older male patients prescribed CPAP therapy for OSA over the last 8 years were reviewed. Compliance was defined by time-counter readings averaging 5 or more hours of machine run-time per night. RESULTS: Of 33 older male patients with OSA studied, 20 were found to be compliant and 13 noncompliant with nasal CPAP therapy. The mean age (+/- SEM) at the time of diagnosis of OSA in the compliant group was 68 (+/-1) years, whereas that of the noncompliant group was 72 (+/-1) years (P <.05). Of the compliant patients, 95% attended a CPAP patient education and support group, whereas only 54% of noncompliant patients attended (P =.006). Resolution of initial symptoms of OSA with CPAP therapy was significantly associated with compliance. Symptom resolution occurred in 90% of compliant patients and in only 18% of noncompliant patients (P <.0002). Factors that were significantly associated with noncompliance with CPAP were cigarette smoking, nocturia, and benign prostatic hypertrophy (BPH). Of noncompliant patients, 82% complained of nocturia, whereas only 33% of compliant patients complained of nocturia (P =.02). BPH was diagnosed in 62% of noncompliant patients and in only 15% of compliant patients (P =.004). Diuretic use was more common in the compliant group and, therefore, was not a cause of increased nocturia in noncompliant patients. CONCLUSION: In older male patients with OSA, compliance with CPAP therapy is associated with attendance at a patient CPAP education and support group. Resolution of symptoms with therapy also appears to be associated with enhanced compliance. In addition, we found an association between nocturia and the existence of BPH in older men with OSA who are not compliant with nasal CPAP. Larger observational studies should be performed to confirm these findings, and, if so confirmed, then further studies to determine whether treatment of BPH in older men with OSA improves compliance with CPAP.     

Sleepiness and nocturnal hypoxemia in Peruvian men with obstructive sleep apnea

Purpose

To evaluate the intensity of nocturnal hypoxemia associated with sleepiness in Peruvian men with a diagnosis of obstructive sleep apnea (OSA).

Methods

We carried out a secondary data analysis based on a study which includes patients with OSA who were seen in a private hospital in Lima, Peru from 2006 to 2012. We included male adults who had polysomnographic recordings and who answered the Epworth sleepiness scale (ESE). The intensity of nocturnal hypoxemia (oxygen saturation ≤90 %) was classified in four new categories: 0, <1, 1 to 10 and >10 % total sleep time with nocturnal hypoxemia (NH). When the ESE score was higher than 10, we used the definitions presence or absence of sleepiness. We used Poisson regression models with robust variance to estimate crude and adjusted prevalence ratios (PR) for association between sleepiness and NH.

Results

518 male patients with OSA were evaluated. Four hundred and fifty-two (87 %) patients had NH and 262 (51 %) had sleepiness. Of the 142 (27.4 %) patients who had >10 % total sleep time with NH, 98 (69.0 %) showed sleepiness and had a greater probability of sleepiness prevalence, with a crude PR of 1.82 (95 % CI 1.31–2.53). This association persisted in the multivariate models.

Conclusions

We found an association between NH and sleepiness. Only patients with the major intensity of NH (over 10 % of the total sleep time) had a greater probability of sleepiness. This suggests that sleepiness probably occurs after a chronic process and after overwhelming compensatory mechanisms.     

Determinants of chronic hypercapnia in Japanese men with obstructive sleep apnea syndrome

STUDY OBJECTIVE: To identify the determinants of chronic hypercapnia (ie, PaCO(2), > or = 45 mm Hg) in men with obstructive sleep apnea syndrome (OSAS) without airflow obstruction. DESIGN: An analysis was conducted of 143 male patients with OSAS, which had been diagnosed by polysomnography (PSG), who had been referred to a university hospital. Patients were classified as hypercapnic (ie, PaCO(2), > or = 45 mm Hg) and normocapnic (ie, PaCO(2), < 45 mm Hg), and obese (ie, body mass index [BMI], > or = 30 kg/m(2)) or nonobese (ie, BMI, < 30 kg/m(2)). Patients with airflow obstruction (ie, FEV(1)/FVC ratio, < 70%) were excluded from the study. Baseline clinical characteristics, pulmonary function, PSG data, and blood gas data were compared between hypercapnic and normocapnic patients. Correlations between PaCO(2) and several anthropometric, respiratory, and polysomnographic variables were determined by stepwise multiple regression analysis. RESULTS: Fifty-five patients (38%) were hypercapnic. Hypercapnic patients were younger and heavier, and had more abnormalities on pulmonary and PSG testing. Stepwise multiple regression analysis revealed that the PaCO(2) level was influenced significantly by the mean level of arterial oxygen saturation (SaO(2)) during sleep and by the percent of vital capacity (%VC) (R(2) = 0.430; p < 0.0001), indicating that 43% of the total variance in the PaCO(2) could be explained by the mean SaO(2) and %VC in hypercapnic patients. In contrast, only 13% of the total variance in the PaCO(2) was accounted for by the mean SaO(2) and BMI in normocapnic patients (R(2) = 0.134; p = 0.0034). The mean SaO(2), %VC, and PaO(2) were selected as independent variables for predicting the PaCO(2) in obese patients. These variables explained 41% of the total variance in the PaCO(2) (R(2) = 0.407; p < 0.0001), whereas the mean SaO(2) only accounted for 13% of the total variance in PaCO(2) levels in nonobese patients (R(2) = 0.134; p = 0.0064). CONCLUSION: Nocturnal desaturation and restrictive pulmonary impairment play major roles in determining the PaCO(2) in hypercapnic and obese OSAS patients without airflow obstruction.     

Mortality and apnea index in obstructive sleep apnea. Experience in 385 male patients

Although obstructive sleep apnea (OSA) has been studied in detail for over a decade, the mortality of this disorder is unclear. We calculated cumulative survival in 385 male OSA patients. We found that those with an apnea index (AI) greater than 20 had a much greater mortality than those with AI = less than 20. The probability of cumulative eight-year survival was .96 +/- 0.02 (SE) for AI = less than 20 vs. 63 +/- 0.17 for AI greater than 20 (p less than .05). This difference in mortality related to AI was particularly true in the patients less than 50 years of age in whom mortality from other causes is not common. None of the patients treated with tracheostomy or nasal CPAP died. Eight of the patients treated with uvulopalatopharyngoplasty (UPPP) died and the cumulative survival of the UPPP-alone treated group was not different from the survival curve of untreated OSA patients with an apnea index of greater than 20. We conclude that OSA patients with an apnea index of greater than 20 have a greater mortality than those below 20 and that UPPP patients be restudied after therapy. If the latter patients are found not to have marked amelioration of their AI, then they should be treated by nasal CPAP or tracheostomy.     

Long-term outcome for obstructive sleep apnea syndrome patients. Mortality

As the actual mortality and morbidity of obstructive sleep apnea syndrome (OSAS) have been unknown heretofore, we undertook a follow-up study of 198 OSAS patients seen at the Stanford Sleep Disorders Clinic between 1972 and 1980, for whom either tracheostomy (71 patients) or weight loss (127 patients) had been recommended. At five-year follow-up, all of the deaths (14) had occurred among those conservatively treated with weight-loss (a mortality rate of 11 per 100 patients per five years). These patents also had a higher five-year crude vascular mortality rate: 6.3 per 100 patients per five years, with an age-standardized vascular mortality rate of 5.9 per 100 patients per five years (95 percent confidence interval [CI] 2.5-11.6) vs 0 per 100 for the surgically treated population; this despite a lower mean apnea index (43 versus 69) and a lower mean body mass index (31 versus 34 kg/m2) in the conservatively treated group. With the fictional adjunction of one possible death at five-year follow-up in the surgically treated group, the age-adjusted odds of vascular mortality at five years for the conservatively treated group was 4.7. Our data therefore encourage "aggressive" treatment for patients with OSAS.     

Prevalence of sleep-disordered breathing and sleep apnea in middle-aged urban Indian men

No data are available on the prevalence of sleep-disordered breathing (SDB) and obstructive sleep apnea-hypopnea syndrome (OSAHS) in Indians. We conducted a two-phase cross-sectional prevalence study for the same in healthy urban Indian males (35-65 years) coming to our hospital in Bombay for a routine health check. We also investigated its risk factors and evaluated the significance of the most commonly asked questions that best correlated with the presence of OSAHS. In the first phase, 658 subjects (94%) returned completed questionnaires regarding their sleep habits and associated medical conditions. In the second phase, 250 of these underwent an overnight home sleep study. The estimated prevalence of SDB (apnea-hypopnea index of 5 or more) was 19.5%, and that of OSAHS (SDB with daytime hypersomnolence) was 7.5%. Multiple stepwise logistic regression determined body mass index, neck girth, and history of diabetes mellitus as the principal covariates of SDB. The presence of snoring, nocturnal choking, unrefreshing sleep, recurrent awakening from sleep, daytime hypersomnolence, and daytime fatigue was each statistically significant for identifying patients with OSAHS. The higher prevalence of OSAHS in urban Indian men is striking and may have major public health implications in a developing country.     

Insulin resistance and adipose-derived hormones in young men with untreated obstructive sleep apnea

Purpose

Obstructive sleep apnea (OSA) increases the risk for insulin resistance (IR). The mechanisms that link the two are not clear and are frequently confounded by obesity. OSA is associated with alterations in adipose-derived hormones (adipokines) that increase IR; however, previous studies have focused on middle-aged and older adults. The objective of this study was to determine if IR and alterations in adipokines exist in young men with OSA, independent of obesity.

Methods

Subjects were assigned into the following groups based on body mass index and presence of OSA: obese with OSA (OSA, n?=?12), obese without OSA (NOSA, n?=?18), and normal weight without OSA (CON, n?=?15). Fasting blood was obtained for batch analysis of biomarkers of IR. The homeostasis model assessment (HOMA) method was used to assess IR.

Results

HOMA and leptin were higher in the OSA group than the CON group. There were no differences in insulin, tumor necrosis factor alpha (TNF-α), and interleukin-6 (IL-6) between the OSA and NOSA groups. Adiponectin was lower in the OSA group vs. NOSA and CON; however, when controlled for central abdominal fat (CAF), the difference was nullified. When controlled for total body adiposity, however, CAF was 24 % higher in the subjects with OSA vs. subjects without OSA.

Conclusions

These findings suggest that excess CAF in young men with OSA may contribute to risk for type 2 diabetes indirectly by a degree that would otherwise not be reached through obesity, although further research is needed.     

老年男性阻塞性睡眠呼吸暂停综合征患者骨质疏松症发生风险

目的 旨在探索老年男性阻塞性睡眠呼吸暂停综合征（OSAS）患者骨质疏松症的发生风险。方法 自2015年1月～2017年10月,从北京和甘肃6家三甲医院的睡眠中心收集确诊为OSAS的男性患者798例,根据国际骨质疏松基金会骨质疏松风险一分钟测试题（IOF）将患者分为骨质疏松风险组和对照组。对患者进行定期随访（每6个月）。随访终点为发生骨质疏松风险。应用Cox回归分析老年男性OSAS患者骨质疏松的发生风险因素。结果 302例（48.5%）老年男性OSAS患者筛查出骨质疏松风险。与对照组相比,骨质疏松风险组年龄更高,舒张压更低,腰围更小,吸烟比例更多,睡眠参数中平均脉氧饱和度更低,血液指甘油三酯、尿酸和C反应蛋白相比对照组含量更低,颈动脉粥样硬化和慢性阻塞性肺疾病患病率较对照组明显更高,差异有统计学意义（P＜0.05）。Cox比例风险回归分析结果显示,在55个月的中位随访时间中,年龄（HR=1.029,95% CI 1.013～1.045）和颈动脉粥样硬化史（HR=1.547,95% CI 1.157～2.068）是老年男性OSAS患者骨质疏松发生风险的独立危险因素（P＜0.05）;而较高的腰围（HR=0.983,95% CI 0.976～0.990）和平均脉氧饱和度（HR=0.941,95% CI 0.904～0.979）可能是其保护因素（P＜0.05）。结论 OSAS患者容易继发骨质疏松症,增龄及合并颈动脉粥样硬化的老年男性OSAS患者更容易发生骨质疏松症,较高的腰围和平均脉氧饱和度是其保护因素。     

Coagulability in obstructive sleep apnea

BACKGROUND:

Obstructive sleep apnea (OSA) is a common disorder that affects both quality of life and cardiovascular health. The causal link between OSA and cardiovascular morbidity/mortality remains elusive. One possible explanation is that repeated episodes of nocturnal hypoxia lead to a hypercoagulable state that predisposes patients to thrombotic events. There is evidence supporting a wide array of hematological changes that affect hemostasis (eg, increased hematocrit, blood viscosity, platelet activation, clotting factors and decreased fibrinolytic activity).

OBJECTIVE:

To provide a comprehensive review of the current evidence associating OSA with increased coagulability, and to highlight areas for future research.

METHODS:

Keyword searches in Ovid Medline were used to identify relevant articles; all references in the articles were searched for relevant titles. The Web of Science was used to identify articles citing the relevant articles found using the Ovid Medline search. All original peer-reviewed articles, meta-analyses and systematic reviews regarding the pertinent topics between 1990 and present were selected for review.

RESULTS:

Hematocrit, blood viscosity, certain clotting factors, tissue factor, platelet activity and whole blood coagulability are increased in patients with OSA, while fibrinolysis is impaired.

CONCLUSION:

There is considerable evidence that OSA is associated with a procoagulant state. Several factors are involved in the procoagulant state associated with OSA. There is a need for adequately powered clinical studies involving well-matched control groups to address potential confounding variables, and to accurately delineate the individual factors involved in the procoagulant state associated with OSA and their response to treatment.     

睡眠呼吸暂停低通气综合征问卷对阻塞性睡眠呼吸暂停综合征诊断价值

目的 评价阻塞性睡眠呼吸暂停低通气综合征(OSAHS)的流行病学调查表筛查价值.方法 疑似OSAHS的987例患者为研究对象,按照中华医学会呼吸病学分会睡眠学组睡眠呼吸暂停低通气综合征流行病学调查表进行问卷并行多导睡眠监测.将此问卷表进行量化评分,用克隆巴赫信度系数(α系数)进行信度计算,将各相关因素做方差分析及x2检验,筛选出有统计学意义的因素最后做Logistic回归分析.以鼾声中度以上的打鼾及体质量指数≥25 kg/m2为高危,反之为低危,进行敏感性,特异性,假阳性,假阴性,阳性似然比,阴性似然比,阳性预测值等.结果 疑似OSAHS患者987例,其中男800例(81.05％),女187例(18.95％),年龄18～80岁,平均(47±12)岁,平均体质量指数(29±5) kg/m2.＞60岁者156例(15.81％),≤60岁者831例(84.19％).克隆巴赫信度系数(Cronbach'salpha)是0.803,假阳性者20,假阴性者142,真阳性者742,真阴性者83,问卷的敏感性是83.94％,特异性是80.58％,假阳性率19.42％,假阴性率16.06％,阳性似然比4.32,阴性似然比0.20,阳性预测值0.97,阴性预测值0.37,正确率83.59％.结论 该睡眠调查表对OSAHS筛查具有一定意义,可用于临床OSAHS的初筛,尤其适合在社区和基层医院中推广使用.     

A fatty meal aggravates apnea and increases sleep in patients with obstructive sleep apnea

Purpose

The purpose of this study was to investigate the role of a fatty meal before bedtime, on sleep characteristics and blood pressure in patients with obstructive sleep apnea (OSA).

Methods

Recently diagnosed, by full polysomnography (PSG), patients with OSA (n?=?19) were included. These underwent PSG for additional two consecutive nights. Two hours before the PSG examination, a ham and cheese sandwich of 360 kcal was served to all patients, at first night, while a fatty meal of 1,800 kcal was served before the second PSG examination. Comparisons were performed between the last two examinations in terms of PSG data and morning and night blood pressure measurements.

Results

After the fatty meal, a significant increase was observed in total sleep time (p?=?0.026) in the Apnea–Hypopnea Index (AHI) (p?=?0.015), as well as in the absolute number of obstructive and central apneas (p?=?0.032 and p?=?0.042, respectively) compared to the previous night. Conversely, distribution of sleep stages and indices of nocturnal hypoxia (average and minimum SpO₂ and sleep time with SpO₂?<?90 %) did not change significantly. Likewise, no significant change was observed in blood pressure measurements.

Conclusions

Fatty meal intake before sleep can increase AHI in OSA patients, although it does not affect sleep architecture or indices of hypoxia.     

Craniofacial obesity in patients with obstructive sleep apnea

Introduction  Obstructive sleep apnea (OSA) and obesity are serious, widespread public health issues. Objective  To localize and quantify geometric morphometric differences in facial soft tissue morphology in adults with and without OSA. Materials and methods  Eighty adult Malays, consisting of 40 patients with OSA and 40 non-OSA controls, were studied. Both groups were evaluated by the attending physician and through ambulatory sleep studies. 3-D stereophotogrammetry was used to capture facial soft tissues of both groups. The 3-D mean OSA and control facial configurations were computed and subjected to principal components analysis (PCA) and finite-element morphometry (FEM). Results  The body mass index was significantly greater for the OSA group (32.3 kg/m² compared to 24.8 kg/m², p < 0.001). The neck circumference was greater for the OSA group (42.7 cm compared to 37.1 cm, p < 0.001). Using PCA, significant differences were found in facial shape between the two groups using the first two principal components, which accounted for 50% of the total shape change (p < 0.05). Using FEM, these differences were localized in the bucco-submandibular regions of the face predominantly, indicating an increase in volume of 7–22% (p < 0.05) for the OSA group. Conclusion  Craniofacial obesity in the bucco-submandibular regions is associated with OSA and may provide valuable screening information for the identification of patients with undiagnosed OSA.