Ryujiro Sasanabe

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;[ge;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≥30/h) (OR: 5.09; 95% CI: 2.67–9.71). Women with OSAS (AHI≥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≥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≥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.

Falling asleep while driving and automobile accidents among patients with obstructive sleep apnea–hypopnea syndrome

Abstract Among 448 patients with obstructive sleep apnea–hypopnea syndrome (OSAHS), 40 patients (8.9%) had been involved in one or more automobile accidents during the preceding 5 years. The main cause of these accidents was falling asleep while driving. Excessive sleepiness during driving was associated with an Epworth sleepiness scale (ESS) score of > 11 and/or an apnea–hypopnea index (AHI) of > 15. The automobile accident rate among 182 patients with severe OSAHS (AHI > 30) was significantly higher than the rate among 106 simple snorers (AHI < 5). Although four of the simple snorers were involved in automobile accidents, their ESS scores were all very high (15 or more).

Prevalence of ischemic heart disease among patients with sleep apnea syndrome

Abstract We investigated the prevalence of ischemic heart disease (IHD) in sleep apnea syndrome (SAS) and the presence of coronary risk factors involved in the onset of IHD in 386 subjects with suspected SAS due to heavy snoring. The prevalence of IHD among patients with untreated SAS was found to be 23.8%, and the percentage of patients having SAS complicated with IHD was high among those with moderate or severe SAS. Sleep apnea syndrome patients with IHD also showed high prevalences of hypertension and hyperlipidemia. It appears that sleep apnea aggravates the factors that cause coronary vascular disorders, and is involved in the onset of IHD.

Multiple cardiovascular risk factors in obstructive sleep apnea syndrome patients and an attempt at lifestyle modification using telemedicine-based education.

Severe obstructive sleep apnea syndrome (OSAS) is a typical ‘lifestyle‐related disease’ characterized by a high incidence of cardiovascular risk factors, such as obesity, smoking, hypertriglyceridemia, and diabetes mellitus. Patients with OSAS tend to have eating disorders as a result of efforts to overcome the intolerable sleepiness. Treatment of OSAS should therefore aim to improve the lifestyle through encouraging weight reduction, physical activity increase, and tobacco avoidance, in addition to direct therapy such as continuous positive airway pressure for upper airway obstruction. The telemedicine system we developed was considered to be effective for providing home‐based education on nutrition and exercise aimed at correcting multiple risk factors in OSAS patients.

Effects of physiological cardiac pacing on sleep-disordered breathing in patients with chronic bradydysrhythmias

In six patients with chronic bradydysrhythmias, polysomnographies were performed before cardiac pacemaker implantation and over the week following implantation. A patient with third‐degree atrioventricular block (AVB) and two patients with sinus node dysfunction (SND) were associated with sleep‐disordered breathing (SDB). Their cardiac pacemaker therapies, with the increase in the average heart rate, led to a reduction of apnea–hypopnea index and/or an improvement of Cheyne‐Stokes breathing. It seems that chronic bradydysrhythmia is one of the causative factors leading to SDB.

Effective three-dimensional evaluation analysis of upper airway form during oral appliance therapy in patients with obstructive sleep apnoea

The oral appliance (OA) is considered to be an effective treatment modality for obstructive sleep apnoea (OSA). Upper airway enlargement during OA therapy is critical, and lateral cephalometry has been used for the two-dimensional evaluation of upper airway form during this therapy. However, this method cannot provide an accurate three-dimensional (3D) view of upper airway form. To confirm the effects of OA on the upper airway in patients with OSAS, we performed CT in the presence and absence of OA in 15 Japanese patients (12 males, 3 females) who responded to OA therapy. CT in the presence and absence of OA was consecutively performed for each patient, and upper airway cross-sectional area in six arbitrary planes parallel to the palatal plane was measured. Next, 3D image reconstruction was performed; morphological changes in upper airway form were evaluated, and upper airway volume at three levels from the palatal plane to the deepest point of the epiglottis was measured. The cross-sectional area of two planes in the posterior soft palate region significantly increased in the presence of OA compared with that in the absence of OA. In the presence of OA, upper airway cross-sectional area and volume significantly increased in the posterior soft palate region compared with those in the posterior tongue region. 3D CT image reconstruction accurately confirmed morphological changes in the upper airway during OA therapy. Continued use of this 3D evaluation is expected to improve the results of OA therapy in the future.

Effect of rapid eye movement-related obstructive sleep apnea on adherence to continuous positive airway pressure

Objective Rapid eye movement (REM)-related obstructive sleep apnea (OSA) is characterized by respiratory events such as apnea and hypopnea predominately or exclusively during REM sleep. Several studies have revealed clinical predictors of adherence to the use of continuous positive airway pressure (CPAP). However, the effect of REM-related OSA on adherence to CPAP use remains unclear. Therefore, we investigated the effects of REM-related OSA on adherence to CPAP use 6 months after treatment initiation. Methods We enrolled 161 patients in this study and divided them into 3 groups: the good adherence, poor adherence, and dropout groups. We compared polysomnographic data and clinical findings, including those regarding morbidity of REM-related OSA, among the three groups to identify predictors of adherence to CPAP use. Results None of the 43 patients in the good adherence group had REM-related OSA. Multivariate logistic regression analysis of the good adherence and dropout groups indicated that REM-related OSA was the only factor associated with adherence to CPAP use (odds ratio, 41.984; 95% confidence interval, 2.257–781.007). Conclusions REM-related OSA is a reliable risk factor for dropout from CPAP therapy.

Gender Differences in the Severity of Sleep Apnea

Although the diagnosis of sleep apnea syndrome (SAS) was defined in the third edition of the International Classification of Sleep Disorders (ICSD-3) (1) published in 2014 by the American Academy of Sleep Medicine, there was no statement about the severity of SAS. Currently, the apneahypopnea index (AHI) is generally used to indicate the severity of SAS; however, there are sex differences in the frequency of occurrence of sleep apnea, which tends to be low in women. The severity of SAS can be determined from the associated complications and/or secondary diseases, and it is problematic to determine the severity using only the AHI, which is the number of apnea or hypopnea events that take place during 1 hour of sleep. For this reason, there was no statement about the severity of SAS in ICSD-3. The prognosis of SAS is related to the onset of ischemic heart disease, congestive heart failure, cerebrovascular disorder, and premature mortality. The onset of these diseases seems to be influenced by complications with hypertension, diabetes, and metabolic syndrome (MetS). Sasanabe et al. (2) studied the relationship between SAS and metabolic syndrome and found a high frequency of severe SAS in patients with MetS. Furthermore, SAS was related to the presence of MetS in men, but no exact relationship was seen in women. In a study of approximately 1,800 subjects, Mieno et al. (3) demonstrated that a higher AHI is a significant risk factor for the development of MetS in both Japanese men and women, but there was only a moderate degree of involvement in women. However, female sex was inversely associated with the prevalence of MetS, independent of other factors, such as apneic severity, suggesting that apnea may make women more resistant to MetS. However, which factors are responsible for this resistance is unknown, and future studies are expected to shed further light on this subject. Intermittent hypoxia has been shown to affect hypertension in sleep apnea (4). However, whether the number of times per hour or the duration of exposure to hypoxia is more influential is unclear at present. Even in patients with the same AHI, there is a wide range in the severity of the decreases in oxygen saturation accompanying apnea and hypopnea, and in some cases, exacerbation only occurs during rapid eye movement sleep. The desaturation is alleviated by aging and exacerbated by an increase in the body mass index (BMI); of note, women typically weigh less than men. Therefore, the severity of SAS cannot be determined based solely on the number of desaturation events. Similar to the estimated glomerular filtration rate for the detection of chronic kidney disease, a new index representing the severity of SAS that considers the prognosis, sex differences, age, increase in the BMI, hypoxia exposure, and the number of apnea or hypopnea events per hour is needed.

Improved accuracy for the detection of sleep apnea-related surges in blood pressure

The severity of obstructive sleep apnea syndrome (OSAS) increases in obese individuals along with the prevalence of complications, such as hypertension, type-2 diabetes, metabolic syndrome and chronic kidney disease,1,2 and these health-related issues lead to an increased risk of cardiovascular and cerebrovascular disease.3 Regarding the effects of OSAS on the cardiovascular system, patients with severe OSAS who continue treatment with continuous positive airway pressure (CPAP) have an improved prognosis, whereas patients who cannot continue CPAP have a clearly worse prognosis.4 In addition, another study has shown a high incidence of nocturnal deaths in OSAS patients.5 To prevent cardiovascular and cerebrovascular disease, risk factors such as metabolic syndrome and chronic kidney disease must be diagnosed early. Blood pressure must be controlled, which involves not only lowering the blood pressure but also minimizing wide fluctuations in blood pressure.6,7 Among middle-aged patients with OSAS, many patients without hypertension during the daytime may exhibit large variations in blood pressure and pulse rates only when breathing resumes by arousal reaction after nocturnal apnea. However, recording these surges in blood pressure at night is difficult with conventional ambulatory blood pressure monitoring (ABPM), which measures blood pressure at fixed intervals. Accordingly, Shirasaki et al.8 developed an ABPM method that detects arterial oxygen desaturation due to apnea and from that point measures blood pressure. However, the measurement algorithm used by Shirasaki et al.8 was weakly correlated with apnea severity, including the duration and severity of apnea itself and the severity of oxygen desaturation. To overcome this deficiency, in another paper, Shirasaki et al.9 proposed to further measure the blood pressure when the degree of oxygen desaturation became even more severe, without setting times when the blood pressure was not measured. This approach offered the advantage of blood pressure measurements corresponding to times when there was severe oxygen desaturation—namely, when there might be a reactive increase in blood pressure. However, by removing fixed times when the blood pressure was not measured, frequently repeated blood pressure measurements could interrupt sleep maintenance. To reduce the frequency of blood pressure measurements, the threshold for oxygen desaturation must be set to large values X10%. The severity of OSAS is evaluated by the apnea–hypopnea index. According to the American Academy of Sleep Medicine Manual for Scoring of Sleep and Associated Events,10 hypopnea is defined as a respiratory event associated with X4% oxygen desaturation. Currently, the degree of oxygen desaturation required to initiate the blood pressure measurement is 10%. The difference between 4 and 10% is large, and thus a considerable number of hypopnea and apnea events are being missed. It is possible that only severe events are being detected, which is a drawback to this approach. Surges in blood pressure in patients with slight arterial oxygen desaturation, such as elderly women with mild heart failure, are probably not being detected. Obese middle-aged patients with OSAS primarily exhibit snoring and have a short history of hypertension. Therefore, a revision of this algorithm may enable the more accurate measurement of nocturnal changes in blood pressure compared with conventional ABPM.

Oral Appliance Therapy for Mild Obstructive Sleep Apnoea Syndrome

Abstract We report a 42-year-old man who was admitted to the Aichi Medical University Hospital, Aichi, Japan, following cardiac arrest and was successfully revived using an automated external defibrillator. Percutaneous catheter intervention was performed and a cardioverter-defibrillator was implanted. The patient was also diagnosed with mild obstructive sleep apnoea syndrome and treated using an oral appliance. His apnoea-hypopnoea index improved from 13.5/ hour to 2.7/hour following the oral appliance treatment, which was continued for more than 3 years after his discharge.