Seiko Miyata

Continuous positive airway pressure improves daytime baroreflex sensitivity and nitric oxide production in patients with moderate to severe obstructive sleep apnea syndrome.

Individuals with obstructive sleep apnea syndrome (OSAS) are at high risk for cardiovascular morbidity and mortality. The effects of OSAS severity and nocturnal continuous positive airway pressure (CPAP) on daytime baroreflex sensitivity (BRS) and nitric oxide (NO) production were investigated in OSAS patients. Fifty-one consecutive males with OSAS and 29 age-matched healthy men underwent the Valsalva test and standard polysomnography. Patients with an apnea-hypopnea index (AHI) of ≥20 episodes per hour were randomized to receive CPAP treatment for 3 months (n=14) or no such treatment (n=19). The BRS index measured from the overshoot phase (phase IV) of the Valsalva maneuver and plasma NO concentration were significantly lower, whereas the AHI, oxygen desaturation time, arousal index, percentage of sleep stage 1, and systolic blood pressure were significantly greater, in patients with an AHI of ≥20/h than in those with an AHI of <20/h or in controls. The 24-h urinary excretion of norepinephrine was significantly reduced and the plasma NO concentration was significantly increased after one night of CPAP. The BRS index for phase IV and the Valsalva ratio were significantly increased in the CPAP group after the 3-month treatment period but remained unchanged in the non-CPAP group of OSAS patients. The daytime BRS index and NO production were thus inversely related to the severity of OSAS, and successful CPAP treatment improved these parameters in patients with moderate to severe OSAS. CPAP may therefore reduce the risk of cardiovascular complications due to endothelial dysfunction or increased sympathetic activity.

Influence of Nasal Resistance on Initial Acceptance of Continuous Positive Airway Pressure in Treatment for Obstructive Sleep Apnea Syndrome

Background: Continuous positive airway pressure (CPAP) is considered as the standard therapy for obstructive sleep apnea syndrome (OSAS), but some patients with OSAS are unable to accept CPAP due to nasal obstruction and poor nasal airflow. Objectives: We assessed the influence of nasal resistance before beginning CPAP treatment on the initial acceptance of CPAP in OSAS patients. Methods: The study subjects comprised 77 patients (74 males, 3 females) with primary OSAS, all of whom received CPAP treatment with nasal masks. Before trials, all subjects underwent overnight polysomnography, and nasal resistance was measured with active anterior rhinomanometry in the seated position on the first day of CPAP trial. Results: The CPAP treatment was accepted by 56 patients after the initial trials with overnight polysomnography. Body mass index, the number of apnea/hypopnea episodes per hour (apnea/hypopnea index; AHI), and the number of episodes per hour with an oxygen desaturation of >3% (oxygen desaturation index) were significantly higher (p < 0.01) and nasal resistance was lower (p = 0.003) in patients who accepted CPAP than in those who did not. Logistic regression analysis, with patient age, body mass index, Epworth sleepiness scale score, AHI, oxygen desaturation index, and nasal resistance before CPAP treatment as explanatory variables, showed that nasal resistance (OR + 0.1 Pa/cm3/s: 1.48; p = 0.002) and AHI (OR + 1 event/h: 0.93; p = 0.003) were significant factors for CPAP non-acceptance. Conclusions: Nasal resistance before the beginning of CPAP treatment has a significant effect on the acceptance of CPAP in OSAS patients, and hence, could be a predictive parameter for the initial acceptance of CPAP.

Poor sleep quality impairs cognitive performance in older adults.

The prevalence of insomnia increases with age. Short sleep duration is associated with deficits in cognitive performance. We hypothesized that short sleep duration and sleep quality influence cognitive performance in older adults. The study included 78 adults aged 60 years and over (72.2 ± 5.9 years). Total sleep time and sleep efficiency (total sleep time/time in bed × 100) were calculated using actigraphy. We evaluated cognitive performance with the continuous performance test‐identical pairs and the number‐back test. Sleep apnea was evaluated overnight with a portable home monitoring system. The accuracy of the 0‐back test significantly decreased in participants with total sleep time less than 5 h compared with those with total sleep time greater than 7 h, but there was no significant difference in continuous performance test‐identical pairs between the two groups. Participants with sleep efficiency <85% showed a significant decrease in 0‐ and 1‐back test accuracy compared with those with sleep efficiency ≥85%. There were no significant differences in the accuracy of number‐back tests and continuous performance test‐identical pairs between apnea–hypopnea index ≥15 h−1 and apnea–hypopnea index <15 h−1 groups, or among lowest SpO2 ≥ 90%, lowest 80–90%, and lowest SpO2 < 80% groups. Age, total sleep time and sleep efficiency were significantly correlated with accuracy on the 0‐back test. Age and sleep efficiency were significantly correlated with accuracy on the 1‐back test. Multiple regression analysis revealed that total sleep time was independently correlated with accuracy on the 0‐back test, while age was independently correlated with accuracy on the 1‐back test. Our findings suggest that sleep duration and sleep quality may play a role in cognitive performance in older adults.

Insufficient sleep impairs driving performance and cognitive function

Cumulative sleep deprivation may increase the risk of psychiatric disorders, other disorders, and accidents. We examined the effect of insufficient sleep on cognitive function, driving performance, and cerebral blood flow in 19 healthy adults (mean age 29.2 years). All participants were in bed for 8h (sufficient sleep), and for <4h (insufficient sleep). The oxyhaemoglobin (oxyHb) level by a word fluency task was measured with a near-infrared spectroscopy recorder on the morning following sufficient and insufficient sleep periods. Wisconsin card sorting test, continuous performance test, N-back test, and driving performance were evaluated on the same days. The peak oxyHb level was significantly lower, in the left and right frontal lobes after insufficient sleep than after sufficient sleep (left: 0.25+/-0.13 vs. 0.74+/-0.33 mmol, P<0.001; right: 0.25+/-0.09 vs. 0.69+/-0.44 mmol, P<0.01). The percentage of correct responses on CPT after insufficient sleep was significantly lower than that after sufficient sleep (96.1+/-4.5 vs. 86.6+/-9.8%, P<0.05). The brake reaction time in a harsh-braking test was significantly longer after insufficient sleep than after sufficient sleep (546.2+/-23.0 vs. 478.0+/-51.2 ms, P<0.05). Whereas there were no significant correlations between decrease in oxyHb and the changes of cognitive function or driving performance between insufficient sleep and sufficient sleep. One night of insufficient sleep affects daytime cognitive function and driving performance and this was accompanied by the changes of cortical oxygenation response.

Aortic Pressure Augmentation as a Marker of Cardiovascular Risk in Obstructive Sleep Apnea Syndrome

Obstructive sleep apnea syndrome (OSAS) is associated with increases in cardiovascular morbidity and mortality. Vascular changes in individuals with OSAS have not been fully elucidated, however. The possible impact of OSAS on the extent of aortic pressure augmentation (AG), an indicator of cardiovascular risk, was investigated. Forty-five consecutive male patients aged 35 to 78 years (56.0±9.6 years) who were referred to the sleep clinic of Nagoya University Hospital for screening and treatment of OSAS and 71 age-matched healthy men were enrolled in the study. AG was derived from the pressure waveform measured at the radial artery by applanation tonometry. The number of apnea and hypopnea episodes per hour (apnea-hypopnea index [AHI]) was determined by standard polysomnography. AG was significantly greater in OSAS patients than in controls (9.0±4.1 vs. 6.4±3.4 mmHg, p<0.001), and it was significantly reduced in 19 OSAS patients treated with continuous positive airway pressure. AG was also significantly correlated with the AHI (r=0.562, p<0.001) and age (r=0.356, p=0.016) but not with the serum concentrations of low and high density lipoprotein-cholesterol, triglyceride, or glycosylated hemoglobin. Stepwise multiple regression analysis revealed that the AHI was the most significant contributing factor to the increased AG in OSAS patients (β=0.109, r=0.530, p<0.001). OSAS may thus have an adverse effect on vascular function that can be ameliorated by appropriate treatment.

Relation of a common variant of the adiponectin gene to serum adiponectin concentration and metabolic traits in an aged Japanese population

Adiponectin is an adipocyte-derived protein that is down-regulated in obesity-linked disorders. Variants of the adiponectin gene (ADIPOQ) have been shown to affect adiponectin level. We have now examined the relation of polymorphisms of ADIPOQ to adiponectin concentration and to metabolic disorders in the Kita-Nagoya Genomic Epidemiology study, a population-based study of elderly Japanese. The genomic region including ADIPOQ was genotyped for 30 single nucleotide polymorphisms in 500 subjects of a screening population with the use of a fluorescence- or colorimetry-based allele-specific DNA primer–probe assay system. Four polymorphisms were then selected for genotyping in an additional 2797 subjects. Serum adiponectin level was negatively associated with metabolic abnormalities after adjustment for age and sex. The minor alleles of the rs1656930, Ile164Thr, and rs9882205 polymorphisms were associated with a low serum adiponectin level. Whereas the minor alleles of rs1656930 and rs9882205 were common (minor allele frequency of 6.2 and 38.5%, respectively), that of Ile164Thr was rare (0.9%). The minor allele of rs1656930 was positively associated with systolic blood pressure and the prevalence of hypertension. The association of rs1656930 with adiponectin level was replicated in an independent population. A subject with the 164Thr/Thr genotype had an extremely low serum adiponectin level (0.6 μg/ml) and the phenotype of metabolic syndrome. Our results suggest that a common variant of ADIPOQ, the minor allele of rs1656930, is associated with hypoadiponectinemia and hypertension. Screening for a common genetic background underlying low adiponectin levels might provide important information for assessment and management of metabolic disorders.

The ratio of adiponectin to homeostasis model assessment of insulin resistance is a powerful index of each component of metabolic syndrome in an aged Japanese population: Results from the KING Study

We evaluated the ratio of adiponectin level to homeostasis model assessment of insulin resistance (A/H ratio) as a risk marker for metabolic syndrome (MetS) and each of its components. The A/H ratio may prove to be a powerful index for evaluation of risk for MetS and each of its components.

Therapeutic Strategies for Sleep Apnea in Hypertension and Heart Failure

Sleep-disordered breathing (SDB) causes hypoxemia, negative intrathoracic pressure, and frequent arousal, contributing to increased cardiovascular disease mortality and morbidity. Obstructive sleep apnea syndrome (OSAS) is linked to hypertension, ischemic heart disease, and cardiac arrhythmias. Successful continuous positive airway pressure (CPAP) treatment has a beneficial effect on hypertension and improves the survival rate of patients with cardiovascular disease. Thus, long-term compliance with CPAP treatment may result in substantial blood pressure reduction in patients with resistant hypertension suffering from OSAS. Central sleep apnea and Cheyne-Stokes respiration occur in 30–50% of patients with heart failure (HF). Intermittent hypoxemia, nocturnal surges in sympathetic activity, and increased left ventricular preload and afterload due to negative intrathoracic pressure all lead to impaired cardiac function and poor life prognosis. SDB-related HF has been considered the potential therapeutic target. CPAP, nocturnal O2 therapy, and adaptive servoventilation minimize the effects of sleep apnea, thereby improving cardiac function, prognosis, and quality of life. Early diagnosis and treatment of SDB will yield better therapeutic outcomes for hypertension and HF.

Effects of Aged Garlic Extract on Left Ventricular Diastolic Function and Fibrosis in a Rat Hypertension Model

Daily consumption of garlic is known to lower the risk of hypertension and ischemic heart disease. In this study, we examined whether aged garlic extract (AGE) prevents hypertension and the progression of compensated left ventricular (LV) hypertrophy in Dahl salt-sensitive (DS) rats. DS rats were randomly divided into three groups: those fed an 8% NaCl diet until 18 weeks of age (8% NaCl group), those additionally treated with AGE (8% NaCl + AGE group), and control rats maintained on a diet containing 0.3% NaCl until 18 weeks of age (0.3% NaCl group). AGE was administered orally by gastric gavage once a day until 18 weeks of age. LV mass was significantly higher in the 8% NaCl + AGE group than in the 0.3% NaCl group at 18 weeks of age, but significantly lower in the 8% NaCl + AGE group than in the 8% NaCl group. No significant differences were observed in systolic blood pressure (SBP) between the 8% NaCl and 8% NaCl + AGE groups at 12 and 18 weeks of age. LV end-diastolic pressure and pressure half-time at 12 and 18 weeks of age were significantly lower in the 8% NaCl + AGE group compared with the 8% NaCl group. AGE significantly reduced LV interstitial fibrosis at 12 and 18 weeks of age. Chronic AGE intake attenuated LV diastolic dysfunction and fibrosis without significantly decreasing SBP in hypertensive DS rats.

Sleep and lifestyle habits in morning and evening types of human circadian rhythm

Current lifestyles often involve activities during the day and at night, and disruption of habits and sleep–wake rhythms may result in circadian rhythm disorders. We assessed the sleep habits and lifestyle habits in 52 subjects using the Japanese-language version of Horne and Ostbergs Morningness-Eveningness Questionnaire and the Tokyo Neurosciences General Laboratory Formula Examination of Life Habits. Of the 52 subjects, 9.6% were morning-types, 71.2% were intermediate-types, and 19.2% were evening-types. Of the evening-types, 40% had a variation in sleep time of more than two hours, and 20% had a variation in awakening time of more than two hours. Approximately 80% of the morning-types and 20% of the evening-types reported pleasant awakening experiences. Assessment of actual conditions of sleep and lifestyle habits using simple and highly reliable questionnaires may be useful in the prevention of sleep disorders and in the improvement of sleep and lifestyle habits.