Elevated fractalkine in patients with obstructive sleep apnea hypopnea syndrome

Background

Obstructive sleep apnea hypopnea syndrome (OSAHS) has been increasingly linked to cardiovascular disease. Inflammatory processes associated with OSAHS may contribute to artherosclerosis in these patients. Fractalkine is a unique chemokine which has both adhesive and chemoattractant functions. We tested the hypothesis that OSAHS patients have increased fractalkine.

Methods and results

We studied 20 patients (18 males and 2 females) with newly diagnosed OSAHS, who were free of other diseases, had never been treated for OSAHS, and were taking no medications. We compared fractalkine measurements in these patients to measurements obtained in 15 control subjects (14 males and 1 female) who were matched for age and body mass index, and in whom occult OSAHS was excluded. Plasma fractalkine levels were significantly higher in patients with OSAHS than in controls (463.15?±?110.78 versus 364.67?±?64.81 pg/mL, F?=?2.58, P?=?0.004). Fractalkine were associated with AHI (r?=?0.756, P?<?0.0001), lowest oxygen saturation (r?=??0.466, P?=?0.005), and mean oxygen saturation (r?=??0.344, P?=?0.043). Plasma fractalkine levels were significantly decreased in patients with OSAHS after four nights nCPAP (463.15?±?110.78 versus 416.75?±?97.67 pg/mL, P?=?0.001).

Conclusions

OSAHS is associated with elevated levels of fractalkine, a marker of inflammation related to artherosclerosis. The severity of OSAHS is proportional to the fractalkine level.     

阻塞性睡眠呼吸暂停低通气综合征对患者心肌缺血负荷的影响

目的探讨阻塞性睡眠呼吸暂停低通气综合征(OSAHS)对患者心肌缺血的影响及可能机制。方法纳入52例OSAHS患者和21名健康体检者,应用多导睡眠监测系统(PSG)行至少7 h睡眠呼吸监测,长程动态心电图(Holter)同步记录心电动态变化,分析心肌缺血与呼吸紊乱指数(AHI)的关系。结果轻中度OSAHS组(5次/h≤AHI<30次/h)与重度OSAHS组(AHI≥30次/h)均表现为睡眠时心肌缺血负荷显著大于觉醒时,且OSAHS患者AHI与睡眠时心肌缺血负荷相关(r=0.667,P<0.01)。轻中度OSAHS组与重度OSAHS组分别根据有无心肌缺血情况,分为心肌缺血组和无心肌缺血组。轻中度组亚组分析显示,与无心肌缺血组相比,心肌缺血组清醒时与睡眠时的平均心率均显著增快[(83.33±6.86)次/min比(76.30±8.52)次/min;(64.71±6.94)次/min比(59.18±2.94)次/min,均为P<0.05]。重度组亚组分析显示,与无心肌缺血组相比,心肌缺血组睡眠效率(74.71%±8.32%比86.36%±6.33%,P<0.01)、最低血氧饱和度(52.36%±17.32%比64.80%±14.86%,P<0.05)、平均血氧饱和度(87.93%±4.80%比92.00%±1.73%,P<0.01)及总非快速动眼期时间/总睡眠时间(68.67%±4.19%比76.87%±7.16%,P<0.05)均显著降低,SaO_2<90%的时间及最长呼吸暂停时间[(236.65±132.72)min比(124.10±82.99)min;(71.63±15.94)s比(55.28±22.05)s,均为P<0.05]均显著延长。结论 OSAHS患者睡眠时的心肌缺血与阻塞性睡眠呼吸暂停相关。轻中度OSAHS患者睡眠时心肌缺血可能由反复交感神经系统激活相关的改变所致,重度OSAHS患者的心肌缺血可能与低氧血症及睡眠结构紊乱相关。     

Increased prevalence of obstructive lung disease in patients with obstructive sleep apnea

Study purposes

This study aims to determine whether there is an increased prevalence of obstructive lung diseases (OLDs) in patients with obstructive sleep apnea (OSA). We also determined whether among the OLD patients there is a difference in the prevalences of specific chronic disease co-morbidities between patients with and without OSA.

Methods

The prevalences of COPD, asthma, and COPD combined with asthma (ICD-9 coding) were compared between 1,497 adult OSA patients and 1,489 control patients, who were matched for age, gender, geographic location, and primary care physician. The prevalences of specific co-morbidities were measured in the OLD groups between patients with OSA and the matched control group.

Results

COPD, asthma, and COPD combined with asthma were found to be more prevalent among OSA patients compared to the matched controls. Prevalences among patients with and without OSA, respectively, were COPD—7.6 and 3.7 % (P?<?0.0001), asthma—10.4 and 5.1 % (P?<?0.0001), COPD plus asthma—3.3 and 0.9 % (P?<?0.0001). The Charlson Comorbidity Index was greater for OSA patients (2.3?±?0.2) than for controls (1.9?±?1.8; P?<?0.0001). These trends held for all severity ranges of OSA. Patients with OSA and COPD were characterized by more severe hypoxia at night compared with the OSA patients without OLD.

Conclusion

OSA was associated with an increased prevalence of OLDs.     

Prevalence of concomitant sleep disorders in patients with obstructive sleep apnea

We determined the prevalence of concomitant sleep disorders in patients with a primary diagnosis of obstructive sleep apnea (OSA). We retrospectively analyzed 643 patients, aged 18, with a primary diagnosis of OSA, evaluated by sleep specialists, in whom clinical and polysomnographic data were derived using standardized techniques by reviewing data from a standardized database and clinical charts. Concomitant sleep disorders were listed according to the International Classification of Sleep Disorders (American Academy of Sleep Medicine, 2000). The mean age was 48.5±13.5 years and 55% were male. Racial distributions were African–Americans 51.8% and Caucasian 47%. Indices of disordered breathing were respiratory disturbance index 32.4±30.4/h sleep and time <90% O₂ saturation 44.5±81.6 min. Thirty-one percent of patients had a concomitant sleep disorder. The most common were inadequate sleep hygiene (14.5%) and periodic limb movement disorder (PLMD, 8.1%). Of patients with other sleep disorders, 66.8% had treatment initiated for these disorders. Predictors of inadequate sleep hygiene (logistic regression) were: age (each decade OR=0.678, P=0.000000), gender (for M, OR=0.536), and the presence of at least one other major system disorder (OR=2.123, P=0.0015). Predictors of PLMD were: age (each decade OR=0.794, P=0.0005), gender (for M, OR=0.433, P=0.004), and total sleep time (for each 10 min, OR=0.972, P=0.0013). We conclude that approximately one third of patients with sleep apnea have another identifiable sleep disorder, usually requiring treatment. This suggests that practitioners evaluating and treating sleep apnea ought to be prepared to deal with other sleep disorders as well.     

Overlap syndrome: obstructive sleep apnea in patients with chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) and sleep apnea-hypopnea syndrome (SAHS) are both common diseases affecting respectively 10 and 5% of the adult population over 40 years of age, and their coexistence, which is denominated overlap syndrome, can be expected to occur in about 0.5% of this population. A recent epidemiologic study has shown that the prevalence of SAHS is not higher in COPD than in the general population, and that the coexistence of the two conditions is due to chance and not through a pathophysiologic linkage between these two diseases. Patients with overlap have a more important sleep-related O(2) desaturation than do patients with COPD with the same degree of bronchial obstruction. They have an increased risk of developing hypercapnic respiratory insufficiency and pulmonary hypertension when compared with patients with SAHS alone and with patients with "usual" COPD. In patients with overlap, hypoxemia, hypercapnia, and pulmonary hypertension can be observed in the presence of mild to moderate bronchial obstruction, which is different from "usual" COPD. Therapy of the overlap syndrome consists of nasal continuous positive airway pressure or nocturnal noninvasive ventilation (NIV), with or without associated nocturnal O(2). Patients who are markedly hypoxemic during daytime (Pa(O(2)) < 55-60 mm Hg) should be given conventional long-term O(2) therapy in addition to nocturnal ventilation.     

Elevated production of tumor necrosis factor-alpha by monocytes in patients with obstructive sleep apnea syndrome

STUDY OBJECTIVES: Tumor necrosis factor (TNF)-alpha is involved in the pathogenesis of atherosclerosis. In the present study, we examined TNF-alpha production by monocytes, serum levels of TNF-alpha, and the effects of nasal continuous positive airway pressure (nCPAP) in patients with obstructive sleep apnea syndrome (OSAS). DESIGN: Prospective observational study. SETTING: University hospital. SUBJECTS: Twenty-four patients with OSAS, 15 obese control subjects, and 12 healthy subjects. MEASUREMENTS AND RESULTS: After polysomnography, venous blood was collected at 5 am. Spontaneous production of TNF-alpha by monocytes for 24 h and serum levels of TNF-alpha were investigated. In addition, patients with moderate-to-severe OSAS were treated with nCPAP for 1 month, and spontaneous production of TNF-alpha by monocytes and serum levels of TNF-alpha were also measured. Spontaneous production of TNF-alpha by monocytes was significantly higher in patients with moderate-to-severe OSAS than in patients with mild OSAS (p < 0.0001), obese control subjects (p < 0.0001), or healthy subjects (p < 0.0001). Serum levels of TNF-alpha were also significantly higher in patients with moderate-to-severe OSAS than in patients with mild OSAS (p < 0.03), obese control subjects (p < 0.0005), or healthy subjects (p < 0.0001). Duration of hypoxia during total sleep time was independently associated with spontaneous production of TNF-alpha by monocytes in patients with OSAS and healthy and obese control subjects. nCPAP significantly decreased spontaneous production of TNF-alpha by monocytes (p < 0.03) and serum levels of TNF-alpha (p < 0.05) in patients with moderate-to-severe OSAS. CONCLUSIONS: Spontaneous production of TNF-alpha by monocytes and serum levels of TNF-alpha are elevated in patients with moderate-to-severe OSAS but are decreased by nCPAP.     

Elevated C-reactive protein levels and increased cardiovascular risk in patients with obstructive sleep apnea syndrome

Obstructive sleep apnea syndrome (OSAS) is associated with cardiovascular morbidity and mortality. Inflammatory processes associated with OSAS may contribute to cardiovascular morbidity in these patients. C-reactive protein (CRP) is an important serum marker of inflammation. We tested the hypothesis that patients with OSAS have increased plasma CRP. After 173 male subjects underwent polysomnography, 94 were considered to have OSAS (apnea-hypopnea index (AHI) > 5), 38 cardiovascular disease (CVD), and 56 without CVD. Seventy-nine subjects were considered not to have OSAS (AHI < 5) and from among these 57 patients without CVD were enrolled as control subjects. Serum CRP levels were significantly elevated in the OSAS + CVD group compared to the two other groups (P < 0.05). When we evaluated the association between the serum CRP level and severity of OSAS, CRP levels were positively correlated with AHI in OSAS patients (r = 0.61, P < 0.001) OSAS, as a marker of inflammation and cardiovascular risk, is associated with elevated levels of CRP. According to these results, the link between cardiovascular morbidity and OSAS may be explained by the coexistence of other cardiovascular risk factors such as circulating CRP levels.     

Oxidative stress in patients with obstructive sleep apnea syndrome

Purpose

We aimed to investigate whether systemic oxidative stress is increased in patients with obstructive sleep apnea syndrome (OSAS).

Methods

A total of 18 patients with severe OSAS and 13 controls were included in the study. Inclusion criteria for OSAS patients were: snoring and apnea–hypopnea index (AHI) of >30 in full polysomnography, no previous treatment for OSAS, non-smoking status, and a medical history of being free of comorbidities known to increase oxidative stress. Controls were recruited among subjects assessed for snoring in the Sleep Laboratory Department if they had AHI<5. At baseline, patients were evaluated by the Epworth Sleepiness Scale and underwent spirometry, echocardiography, and full polysomnographic study. Blood samples were collected for evaluation of oxidative stress biomarkers [protein carbonyls, reduced (GSH) and oxidized (GSSG) glutathione, 8-isoprostane, thiobarbituric acid-reactive substances (TBARS), catalase activity, Cu–Zn superoxide dysmutase (SOD), total antioxidant capacity (TAC)] before and on the morning following polysomnography.

Results

The overnight (morning–night) change (%) of GSH/GSSG ratio and GSH was significantly different between OSAS and controls (p?=?0.03 and p?=?0.048, respectively). Plasma protein carbonyls, erythrocyte catalase activity, 8-isoprostane, SOD, TBARS, and TAC plasma values were not different between OSAS and controls (p?>?0.05). No significant correlation was found between changes in the levels of biomarkers and AHI, arousal, or desaturation index.

Conclusion

The present prospective investigation in a population free of comorbidities or factors which may increase systemic oxidative stress provides evidence that obstructive sleep apnea per se might be associated with increased oxidative burden possibly via GSH/GSSG pathway.     

CPAP compliance in patients with obstructive sleep apnea syndrome

Obstructive sleep apnea syndrome (OSAS) is characterized by repeated cessations of breathing during sleep. Major symptoms of this disease are excessive daytime sleepiness, snoring, and witnessed apnea. Most of the patients are treated with CPAP. In this study, we aimed to evaluate the factors affecting adherence to the CPAP treatment. Seventy-one patients were enrolled to this study. Patients were divided into three groups according to CPAP usage. Group I consisted of patients who had never used CPAP, group II consisted of patients who had used CPAP occasionally, and group-III patients had used CPAP treatment regularly. Group-III patients had higher apnea–hypopnea index (AHI) than groups I and II (respectively, 56.6 ± 27.7, 26.3 ± 7.5, and 32.3 ± 7.06; p < 0.000 for both). Oxygen desaturation index was significantly higher in group-III patients comparing to groups I and II (44.6 ± 22.3, 15.9 ± 8.3, and 25.6 ± 9.5; p < 0.000 for all). Our findings have shown that only very severe patients use the CPAP device regularly (mean AHI 56.6 ± 27.7). Compliance to CPAP treatment seemed to be poor in patients with moderate to severe, AHI about 30, OSAS. Considering the well-established benefits of CPAP treatment in patients with true indications, patients should be encouraged to use CPAP regularly, and complications of OSAS should be keynoted.     

Homocysteine levels in patients with obstructive sleep apnea syndrome

The exact mechanism of development of cardiovascular disease in patients with obstructive sleep apnea syndrome (OSAS) remains to be unknown. The role of homocysteine in atherosclerotic disease process has become well established over the past ten years. Our aim was to study to compare homoscysteine levels between OSAS and control levels. Sixty-two subjects with OSAS and twelve similar controls in age, gender, body mass index, smoking and coronary heart disease were included in this prospective study. Serum levels of homocysteine (13.5 +/- 6.0 micromol/L vs. 10.2 +/- 2.9 micromol/L, p= 0.03) in the OSAS group were significantly greater than those in the control group. Logistic regression analyses showed that OSAS (Odds ratio: 9.08 95% CI 2.347-35.120; p= 0.001) was independent risk factors for high levels of serum homocysteine in age, smoking status, diabetes mellitus and coronary heart disease. We conclude that homocysteine may be an important factor for development of cardiovascular disease in patients with OSAS.     

老年阻塞性睡眠呼吸暂停低通气综合征并存心肌缺血患者的临床特点和治疗

目的观察老年阻塞性睡眠呼吸暂停低通气综合征(OSAHS)并存冠心病心肌缺血患者的临床特点和治疗疗效。方法选择OSAHS并存冠心病患者135例,分为轻、中、重度组,与单纯冠心病对照组45例进行比较,观察其动态心电图(Holter)变化,单纯药物及药物联合经鼻持续气道内正压通气(nCPAP)治疗效果。结果(1)治疗前各组白天心肌缺血发生率差异无统计学意义(P＞0．05)；夜间中、重度组心肌缺血发生率较对照组明显增高,差异有统计学意义(P＜0．05)。(2)药物治疗1个月,各组内比较,白天心肌缺血发生率明显减少,差异有统计学意义(P＜0．05)；中、重度组夜间心肌缺血发生率无明显减少,差异无统计学意义(P＞0．05)。(3)重度组总心血管复合终点事件发生率55．0%,较轻、中度组和对照组(20．0%、30．0%和24．4%)明显增高,差异有统计学意义(均为P＜0．05)。(4)对中、重度组31例发生心血管复合终点事件患者采用药物配合nCPAP治疗1周,与重度组单纯用药者比较,夜间心肌缺血发生率明显改善(77．4%对42．5%,P＜0．05)。结论老年中、重度OSAHS并存冠心病患者夜间心肌缺血发生率明显增高,重度组总心血管复合终点事件发生率增高。单纯抗心绞痛药物治疗能明显改善OSAHS并存冠心病患者白天心肌缺血症状；但是对中、重度患者夜间心肌缺血疗效不佳。药物配合nCPAP治疗能明显改善中、重度患者夜间心肌缺血,降低心血管复合终点事件发生率。     

老年心血管疾病患者阻塞性睡眠呼吸暂停综合征的评价

目的 评价老年心血管疾病患者阻塞性睡眠呼吸暂停综合征(OSAS)的患病情况和特点,为临床决策提供参考. 方法 采用便携式睡眠监测仪对入住在老年心内科的患者,进行睡眠呼吸监测,了解其阻塞性睡眠呼吸暂停(OSA)的患病情况. 结果 共监测了317例老年心血管疾病患者的夜间睡眠呼吸紊乱情况,得出符合OSA[睡眠呼吸紊乱指数(AHI)≥5]的有281例,占88.6%;符合阻塞性睡眠呼吸暂停综合征(OSAS)[AHI≥5,Epworth量表(ESS)≥9分]的有47例,占14.8%.多元回归分析结果 提示,以OSA严重程度作为因变量,对它影响有显著性意义的是最低血氧饱和度和血氧饱和度下降指数(简称氧减指数),而年龄、习惯性打鼾、嗜睡评分、体质指数(BMI)、血氧饱和度平均值和低于90%的时间对其影响无显著性意义. 结论 老年心血管疾病患者中OSAS具有高的患病率,而且无白天嗜睡症状的OSA的老年人患病率更高.对睡眠呼吸暂停严重程度的独立预测因子是最低血氧饱和度氧减指数,而老年人的年龄、BMI、是否经常打鼾、是否白天嗜睡与OSA的严重程度关系不密切.     

阻塞性睡眠呼吸暂停综合征患者肺功能与夜间低氧血症的关系

目的探讨睡眠呼吸暂停综合征（ＳＡＳ）患者体位及肥胖因素引起的肺功能改变与夜间低氧血症的关系。方法选择确诊为ＳＡＳ患者３４例，分别于坐位和仰卧位检查肺功能和血气分析，整夜多导睡眠仪监测。肺功能、血气指标和理想体重％（ＩＢＷ％）分别与呼吸暂停指数（ＡＩ）、＜９０％Ｔ（ＳａＯ２低于９０％时间占总睡眠时间百分比）进行相关分析。结果患者由坐位改为仰卧位，ＰａＯ２、肺活量（ＶＣ％）、补呼气量（ＥＲＶ）、功能残气量（ＦＲＣ％）、残气容积（ＲＶ％）、肺总量（ＴＬＣ％）均出现有统计学意义的降低。ＡＩ与仰卧位ＶＣ％、ＴＬＣ％呈正相关。＜９０％Ｔ与坐位ＰａＯ２、ＥＲＶ呈负相关。ＩＢＷ％与坐、仰卧位ＶＣ％和ＥＲＶ呈负相关，与坐位ＦＲＣ呈负相关。ＩＢＷ％与＜９０％Ｔ呈正相关。结论伴有肥胖的ＯＳＡＳ患者，体位改变及肥胖因素影响患者肺功能，加重呼吸暂停时的低氧血症     

Overlap syndrome involving obstructive sleep apnea syndrome associated with chronic obstructive pulmonary disease

We reported a case of overlap syndrome involving severe obstructive sleep apnea syndrome (OSAS) associated with chronic obstructive lung disease (COPD). This patient was a 52-year-old heavy smoking man, who had suffered from snoring and apnea for five years, and was admitted to our hospital because of worsening dyspnea. His BMI was 25 Kg/M2, His jaw was very small and he had a narrow upper airway. Chest X-ray showed hyperlucency throughout both lung fields with a markedly dilatation pulmonary arteries. His PaO2 was 62Torr, PaCO2 was 47Torr, FEV(1.0%) was 59%, mean pulmonary artery pressure was 27 mmHg, PSG showed that AHI was 70, were most pronounced during rapid eye movement sleep. He was given a diagnosis of overlap syndrome of OSAS associated with COPD. Generally, Overlap syndrome was believed that chronic bronchitis type (blue bloater) was more frequent than emphysema type. This case was a very rare case, with no obesity, moderate COPD, associated with pulmonary hypertension and hypercapnea, and then to be severe OSAS. However we should be more careful about the OSAS associated with overlap syndrome of the Japanese patients, because to be one factor of exacerbation of respiratory failure.     

Metabolic syndrome in Japanese patients with obstructive sleep apnea syndrome.

We investigated the prevalence of metabolic syndrome in patients with obstructive sleep apnea syndrome (OSAS) referred to a tertiary university-based medical center. A cross-sectional study of patients with a definite diagnosis of OSAS was performed using new diagnostic criteria for metabolic syndrome that were designed for the Japanese population. Clinical features and comorbidities related to metabolic syndrome were compared between 819 patients with OSAS (719 men and 100 women) and 89 control subjects without OSAS. Metabolic syndrome was significantly more common in the patients with OSAS than in the controls (49.5% vs. 22.0% for men, p < 0.01; 32.0% vs. 6.7% for women, p < 0.01). Men with OSAS (apnea-hypopnea index [AHI] > or =5/h) had a higher risk of metabolic syndrome compared with controls (odds ratio [OR]: 3.47; 95% confidence interval [CI]: 1.84-6.53). There was a significantly increased risk of metabolic syndrome in men with moderate OSAS (AHI: 15-29.9/h) (OR: 2.83; 95% CI: 1.42-5.66) and men with severe OSAS (AHI > or =30/h) (OR: 5.09; 95% CI: 2.67-9.71). Women with OSAS (AHI> or =5/h) also had an increased risk of metabolic syndrome (OR: 6.59; 95% CI: 1.47-29.38), and the risk was significantly higher in women with severe OSAS (AHI > or =30/h) (OR 14.00; 95% CI: 2.93-66.82). Risk factors for metabolic syndrome differed by gender: in men, age, body mass index (BMI), and OSAS (AHI > or =15/h) were significantly associated with metabolic syndrome, whereas, in women, BMI was the only risk factor for metabolic syndrome. The increase of metabolic syndrome in Japanese OSAS patients suggests that this patient population is burdened with multiple risk factors for cardiovascular disease.     

阻塞性睡眠呼吸暂停综合征术前评估方法的研究进展

阻塞性睡眠呼吸暂停综合征(obstructive sleep apnea syndrome,OSAS)是一种常见的因郡分或全部上呼吸道反复阻塞引起的睡眠障碍,其特征是睡眠时呼吸气流暂停超过10 s.手术患者合并OSAS可使患者更易发生围手术期并发症.目前OSAS诊断的金标准是多导睡眠图,其术前评估方法有量表法和便携式仪器诊断等多种方法.