Chronic Effects of Adaptive Servo-Ventilation Therapy on Mortality and the Urgent Rehospitalization Rate in Patients Experiencing Recurrent Admissions for Heart Failure　- A Multicenter Prospective Observational Study (SAVIOR-L).

BACKGROUND: This study investigated whether the chronic use of adaptive servo-ventilation (ASV) reduces all-cause mortality and the rate of urgent rehospitalization in patients with heart failure (HF).Methods and Results: This multicenter prospective observational study enrolled patients hospitalized for HF in Japan between 2019 and 2020 who were treated either with or without ASV therapy. Of 845 patients, 110 (13%) received chronic ASV at hospital discharge. The primary outcome was a composite of all-cause death and urgent rehospitalization for HF, and was observed in 272 patients over a 1-year follow-up. Following 1:3 sequential propensity score matching, 384 patients were included in the subsequent analysis. The median time to the primary outcome was significantly shorter in the ASV than in non-ASV group (19.7 vs. 34.4 weeks; P=0.013). In contrast, there was no significant difference in the all-cause mortality event-free rate between the 2 groups. CONCLUSIONS: Chronic use of ASV did not impact all-cause mortality in patients experiencing recurrent admissions for HF.

Nutritional Status and Sleep Quality Are Associated with Atrial Fibrillation in Patients with Obstructive Sleep Apnea: Results from Tokyo Sleep Heart Study.

The prevalence of obstructive sleep apnea (OSA) in patients with atrial fibrillation (AF) has been observed to be much higher than in control participants without AF. Limited data exist regarding the prevalence of AF in patients with OSA. The clinical characteristics, nutritional status, and sleep parameters associated with AF in patients with OSA remain unclear. In this study, we aimed to determine the prevalence and factors associated with AF in patients with OSA from a large Japanese sleep cohort (Tokyo Sleep Heart Study). This was a single-center explorative cross-sectional study. Between November 2004 and June 2018, we consecutively recruited 2569 patients with OSA who underwent an overnight full polysomnography at our hospital. They were assessed using a 12-lead ECG and echocardiography. The clinical characteristics, sleep parameters, and medical history were also determined. Of the OSA patients, 169 (6.6%) had AF. Compared with the non-AF patients, OSA patients with AF were older and male, and they had higher prevalence of a history of alcohol consumption, hypertension, chronic kidney disease, and undernutrition, as well as a reduced ejection fraction. With regard to the sleep study parameters, OSA patients with AF had reduced slow-wave sleep and sleep efficiency, as well as higher periodic limb movements. There were no significant differences in the apnea-hypopnea index or hypoxia index between the two groups. The logistic regression analysis demonstrated that age (OR = 4.020; 95% CI: 1.895-8.527; p < 0.001), a history of alcohol consumption (OR = 2.718; 95% CI: 1.461-5.057; p = 0.002), a high CONUT score (OR = 2.129; 95% CI: 1.077-4.209; p = 0.030), and reduced slow-wave sleep (OR = 5.361; 95% CI: 1.505-19.104; p = 0.010) were factors significantly related to AF. The prevalence of AF in patients with OSA was 6.6%. Age, a history of alcohol consumption, undernutrition, and reduced sleep quality were independent risk factors for the presence of AF in patients with OSA, regardless of the severity of OSA.

Multimodal Telemonitoring for Weight Reduction in Patients With Sleep Apnea: A Randomized Controlled Trial.

BACKGROUND: Telemonitoring the use of CPAP devices and remote feedback on device data effectively optimizes CPAP adherence in patients with OSA. RESEARCH QUESTION: Can expanding the scope of telemonitoring and remote feedback to body weight (BW), BP, and physical activity enhance efforts for BW reduction in Patients with OSA receiving CPAP? STUDY DESIGN AND METHODS: Participants were recruited from patients at 16 sleep centers in Japan with OSA and obesity who were receiving CPAP therapy. Obesity was defined as a BMI of ≥ 25 kg/m2, based on Japanese obesity guidelines. Implementation of CPAP telemonitoring was enhanced with electronic scales, BP monitors, and pedometers that could transmit data from devices wirelessly. Participants were randomized to the multimodal telemonitoring group or the usual CPAP telemonitoring group and were followed up for 6 months. Attending physicians provided monthly telephone feedback calls to the usual CPAP telemonitoring group on CPAP data obtained remotely. In the multimodal telemonitoring group, physicians additionally encouraged participants to reduce their BW, after sharing the remotely obtained data on BW, BP, and step count. The primary outcome was set as ≥ 3% BW reduction from baseline. RESULTS: One hundred sixty-eight participants (BMI, 31.7 ± 4.9 kg/m2) completed the study, and ≥ 3% BW reduction occurred in 33 of 84 participants (39.3%) and 21 of 84 participants (25.0%) in the multimodal telemonitoring and usual CPAP telemonitoring groups, respectively (P = .047). Whereas no significant differences were found between the two groups in the change in office and home BP, daily step counts during the study period were significantly higher in the multimodal telemonitoring group than in the usual CPAP telemonitoring group (4,767 steps/d [interquartile range (IQR), 2,864-6,617 steps/d] vs 3,592 steps/d [IQR, 2,117-5,383 steps/d]; P = .02) INTERPRETATION: Multimodal telemonitoring may enhance BW reduction efforts in patients with OSA and obesity. TRIAL REGISTRY: UMIN Clinical Trials Registry; No.: UMIN000033607; URL: www.umin.ac.jp/ctr/index.htm.

Moderate to severe obstructive sleep apnea is independently associated with inter-arm systolic blood pressure difference: Tokyo Sleep Heart Study.

OBJECTIVE: Obstructive sleep apnea (OSA) is recognized as an independent risk factor for cardiovascular disease. On the other hand, inter-arm systolic blood pressure difference (IAD), inter-ankle systolic blood pressure difference (IAND), and ankle-brachial index (ABI) are all known predictors of cardiovascular events. The aim of the present study was to investigate the association between OSA and four-limb blood pressure differences. METHODS: We conducted this cross-sectional study in a large sleep cohort from Tokyo Sleep Heart Study. In 2643 consecutive patients who visited our sleep clinic for polysomnography between 2005 and 2017, all the patients underwent blood pressure measurement simultaneously in all the four limbs by oscillometric methods. RESULTS: The prevalence rate of IAD ≥10 mmHg was significantly higher in the moderate OSA (15 ≤ apnea-hypopnea index [AHI] < 30) group (4.2%) and severe OSA (AHI ≥ 30) group (4.6%) than that in the no/mild (AHI < 15) OSA group (1.4%). Multivariate logistic regression analysis also identified moderate to severe OSA as being significantly associated with IAD ≥10 mmHg, even after adjustments for confounding variables (moderate OSA: odds ratio [OR], 4.869; 95% confidence interval [CI], 1.080-21.956; P = 0.039; severe OSA: OR, 5.301; 95% CI, 1.226-22.924; P = 0.026). However, there were no significant associations of the OSA severity with IAND ≥15 mmHg or ABI <0.9. CONCLUSIONS: Moderate to severe OSA was independently associated with the IAD, not but with the IAND or ABI.

Comparison of the Apnea-Hypopnea Index Determined by a Peripheral Arterial Tonometry-Based Device With That Determined by Polysomnography　- Results From a Multicenter Study.

Background: Sleep disordered breathing (SDB) is prevalent and associated with increased mortality in patients both with and without cardiovascular disease (CVD). Many portable monitoring devices, including peripheral arterial tonometry (PAT)-based devices, have been developed. Although previous studies have demonstrated that the apnea-hypopnea index (AHI) determined by PAT devices (pAHI) is strongly correlated with AHI determined by polysomnography (AHI-PSG), no data have been reported from a Japanese patient population or patients with CVD. In this study we compared the parameters determined by PAT-based devices with those determined by polysomnography in Japanese patients with CVD. Methods and Results: We enrolled 120 patients undergoing overnight polysomnography at 6 Japanese centers. A PAT-based device was used simultaneously with polysomnography. Polysomnography recordings were scored centrally by a technician in a blinded manner. PAT-based device recordings were scored using an automatic algorithm. There was a strong correlation between pAHI and AHI-PSG (r=0.896; P<0.001) with acceptable agreement. The strong correlation between pAHI and AHI-PSG was observed in patients with CVD (n=55; P=0.849; P<0.001) and without CVD (n=65; r=0.927; P<0.001). The presence or absence of CVD did not affect the relationship between pAHI and AHI-PSG (P=0.225). Conclusions: A PAT-based device provides a reliable AHI in a Japanese patient population, even in patients with CVD. These findings may help reduce the number of patients with undiagnosed SDB and CVD.

Role of dental sleep medicine in management of patients with obstructive sleep apnea disorders using a team approach.

OBJECTIVE: Obstructive sleep apnea (OSA) is a significant social and health issue. An integrated multidisciplinary approach to OSA management may be the most effective owing to its multifactorial etiology. In this study, we evaluated the frequency and efficacy of various treatment modalities for OSA administered via an integrated care delivery model, and assessed the role of dental sleep medicine as part of a multidisciplinary team. MATERIALS AND METHODS: We retrospectively evaluated 1115 patients with OSA treated at the Tokyo Medical University Hospital's Outpatient Clinic for OSA by a multidisciplinary team under one roof. The various treatment methods included the following: continuous positive airway pressure (CPAP), oral appliance (OA), surgery, and behavioral treatment. RESULTS: The patient number of study group was as follows: 771 (69.1%) CPAP; 240 (21.5%) OA; 76 (6.8%) behavioral treatment and 28 (3%) surgery. Because significantly fewer patients underwent surgery, there was a discrepancy between the recommended first-choice treatment and the actual treatment. A statistically significant number of younger patients in each treatment group underwent surgery. Success rate of OA and MMA were 74.4 and 80%, respectively. CONCLUSIONS: Proper selection of primary treatment to manage patients with OSA was possible under one-roof system that included dental sleep medicine.

Liver stiffness and arterial stiffness/abnormal central hemodynamics in the early stage of heart failure.

BACKGROUND: It remains to be clarified whether liver stiffness is a direct risk factor for heart failure (HF) or whether its association with HF is mediated by vascular damage. We conducted cross-sectional and prospective longitudinal studies to examine whether fibrosis 4 score (FIB-4 score) is directly associated with the serum NT-pro-BNP levels or the association is mediated by arterial stiffness and/or abnormal central hemodynamics. METHODS AND RESULTS: In 3040 health Japanese subjects with serum NT-pro-BNP levels < 125 pg/ml, the FIB-4 score was calculated, and the serum NT-pro-BNP levels, brachial-ankle pulse wave (baPWV) velocity and radial augmentation index (rAI) were measured. These parameters were measured again after a 3-year interval in 2135 subjects. Multivariate linear regression analysis demonstrated a significant cross-sectional association of the FIB-4 scores with the log-transformed the serum NT-pro-BNP levels (beta = 0.08, p < 0.01), but not with the baPWV or rAI. The change of serum NT-pro BNP levels during the study period was significantly higher in subjects with increase of the FIB-4 score during the study period (8.2 ±â€¯22.5 pg/ml) than that in those with decrease/no change (5.4 ±â€¯22.3 pg/ml) (p < 0.05). CONCLUSION: Liver stiffness may have a significant direct association with the development of HF from the early stage, without the mediation of arterial stiffness and/or abnormal central hemodynamics. Therefore, the FIB-4 score appears to serve as a direct risk factor for HF from the early stage, and its association with HF may not be mediated by vascular damages.

Obstructive Sleep Apnea as Possible Causal Factor for Visit-to-Visit Blood Pressure Variability.

BACKGROUND: Recent studies have shown that visit-to-visit blood pressure variability (BPV) is an independent risk factor for cardiovascular disease. However, it has not been clarified whether obstructive sleep apnea (OSA) is associated with visit-to-visit BPV. METHODS AND RESULTS: The 56 subjects with OSA and 26 control subjects without OSA were examined. Office BP was measured on 5 separate consecutive occasions prior to a polysomnography examination. The visit-to-visit BPV was expressed as the standard deviation and the coefficient of variation of the 5 systolic BP measurements. In subjects with an apnea-hypopnea index (AHI) of more than 20 episodes per hour, the visit-to-visit BPV was also measured after the start of continuous positive airway pressure (CPAP) therapy. Overall, the AHI positively correlated with the standard deviation and the coefficient of variation of systolic BP. In a multivariate analysis, the plasma noradrenaline level and the AHI were independently and positively correlated with the standard deviation and the coefficient of variation of the systolic BP. Among the patients who underwent CPAP therapy, good adherence with CPAP therapy significantly reduced the visit-to-visit BPV. CONCLUSIONS: OSA is associated with abnormal visit-to-visit BPV and sympathetic activation seems to be related in some way. (Circ J 2016; 80: 1787-1794).

Nocturnal Intermittent Hypoxia Is Associated With Left Ventricular Hypertrophy in Middle-Aged Men With Hypertension and Obstructive Sleep Apnea.

BACKGROUND: Obstructive sleep apnea (OSA) and left ventricular (LV) hypertrophy are considered to be closely associated. However, the relationship has not yet been fully demonstrated and is hence still controversial. The purpose of this study was to assess in hypertensive male patients the relationship between OSA and cardiac structure using a new index, namely, integrated area of desaturation (IAD), in addition to the apnea-hypopnea index (AHI) that is currently the most frequently used index of sleep-disordered breathing. METHODS: In our cross-sectional study, 223 hypertensive men younger than 65 years with sleep apnea and normal cardiac function were enrolled. All subjects were evaluated by fully attended polysomnography. Cardiac structure and function were evaluated by echocardiography. RESULTS: LV mass index significantly correlated with IAD (r = 0.203, P < 0.05), but not with AHI. Multivariate linear regression analyses showed that IAD, brain natriuretic peptide (BNP), and age are independent variables affecting the LV mass index (ß = 0.262, 0.237, and 0.173, respectively, P < 0.05). IAD was the one and only determinant among the indices of sleep-disordered breathing. CONCLUSIONS: Nocturnal intermittent hypoxia defined by IAD may be associated with LV hypertrophy in men with well-controlled hypertension and obstructive sleep apnea.

Severe obstructive sleep apnea increases left atrial volume independently of left ventricular diastolic impairment.

PURPOSE: Severe obstructive sleep apnea (OSA) directly impairs left ventricular (LV) diastolic function. Left atrial volume index (LAVI), an independent predictor of future cardiovascular events, is also related to OSA severity. This study aimed to assess whether OSA is associated with an increase in LAVI independently of LV diastolic function. METHODS: Two hundred six OSA patients (apnea hypopnea index, AHI ≥ 5/h) without cardiac disease, hypertension, and diabetes were enrolled. They underwent overnight fully attended polysomnography and 2-dimensional echocardiography in order to estimate LA volumes and LV diastolic function which was assessed by the ratio of transmitral early diastolic flow velocity to late diastolic flow velocity (E/A), deceleration time, and mitral annular velocity (e') which was derived from tissue Doppler imaging. Patients were divided into two groups based on AHI, namely, group M (5 ≤ AHI < 30/h) and group S (AHI ≥ 30/h). RESULTS: The LAVI value in group S was significantly larger than that in group M (20 ± 5 vs. 23 ± 5 mL/m(2), P < 0.001). E/A in group S was significantly lower than that in group M (P < 0.001), whereas the ratio of E to e' (E/e') in group S was significantly higher than that in group M (P < 0.001). AHI showed a statistically significant correlation with LAVI (P < 0.001). On multivariate linear regression analysis, severe OSA was independently related with LAVI even after adjusting for age, sex, systolic blood pressure, body mass index, and measurements of LV diastolic function (P = 0.04). CONCLUSIONS: Severe OSA itself might directly increase LAVI, independently of LV diastolic function.

Continuous positive airway pressure treatment improves cardiovascular outcomes in elderly patients with cardiovascular disease and obstructive sleep apnea.

Obstructive sleep apnea (OSA) is associated with the progression of cardiovascular disease (CVD), particularly in the middle-aged population. However, the clinical importance of OSA as a risk for CVD in the elderly population remains controversial. Moreover, evidence for the effectiveness of continuous positive airway pressure (CPAP) treatment for the secondary prevention of CVD in elderly patients is lacking. We assessed whether CPAP treatment improves cardiovascular outcomes in elderly patients with OSA and CVD. In this retrospective cohort study, we enrolled 130 elderly patients aged 65-86 years with moderate to severe OSA (apnea-hypopnea index ≥15/h) and a history of hospitalization due to CVD, who underwent polysomnography between November 2004 and July 2011. Patients were divided into the CPAP group (n = 64) or untreated OSA group (n = 66). The main outcome measures were cardiovascular death and hospitalization due to CVD. During the mean follow-up period of 32.9 ± 23.8 (standard deviation) months, 28 (21.5 %) patients either died or were hospitalized. The Kaplan-Meier curves indicated that event-free survival was significantly lower in the untreated OSA group than in the CPAP group (P < 0.005). A multivariate analysis showed that the risk was significantly increased in the untreated OSA group (hazard ratio 5.13; 95 % confidence interval 1.01-42.0; P < 0.05). Moderate to severe OSA not treated with CPAP was an independent risk factor for relapse of a CVD event, and adequate CPAP treatment improved cardiovascular outcomes in elderly patients.

Severe obstructive sleep apnea impairs left ventricular diastolic function in non-obese men.

OBJECTIVE: To evaluate whether obstructive sleep apnea (OSA) contributes directly to left ventricular (LV) diastolic dysfunction. METHODS: Seventy-four non-obese male OSA (apnea hypopnea index (AHI)⩾5/h) patients without cardiac disease, hypertension or diabetes were enrolled. Echocardiography, pulse wave velocity (PWV) measurements and laboratory testing were performed in all patients. LV diastolic function was assessed by the transmitral flow velocity (E/A ratio), and mitral annular velocity (Ea) was derived from tissue Doppler imaging (TDI). RESULTS: The E/A ratio and Ea in the severe OSA group (AHI⩾30/h) was significantly lower than those in the mild to moderate OSA group (5⩽AHI<30/h) (P<0.0001), whereas the S/D ratio, an indicator of pulmonary vein flow velocity, in the severe OSA group was significantly higher than that in the mild to moderate OSA group (P=0.04). AHI exhibited a statistically significant inverse correlation with the E/A ratio (r=-0.47, P=0.0001), but not with relative wall thickness (RWT), LV mass index (LVMI) or PWV. RWT, LVMI and PWV exhibited an inverse correlation with the E/A ratio. Multivariate linear regression analysis revealed that severe OSA was independently associated with the E/A ratio even after adjusting for age, insulin resistance, blood pressure, LV geometry, and PWV (ß=-0.23, P=0.001). CONCLUSIONS: These results indicate that severe OSA itself may contribute directly to LV diastolic dysfunction irrespective of LV geometry, arterial stiffness, obesity and its associated cardiovascular risk factors.

Overlap syndrome: additive effects of COPD on the cardiovascular damages in patients with OSA.

The chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (OSA) have been recently much focused as independent risks for cardiovascular disease. Furthermore, the complication of both has a worse prognosis compared with patients with only one of these diseases. However, the details of the underlying mechanisms of this worsened prognosis have not been clear. The cross-sectional study was conducted to examine whether the overlap of COPD augment the increase in arterial stiffness in subjects with OSA. If so, we examined the exaggeration of nocturnal hypoxemia and its related inflammation are related to this augmentation of increased arterial stiffness. In 524 male subjects with OSA diagnosed by polysomnography (apnea-hypopnea index >5/h) (52 ± 14 years old), the forced expiratory volume at 1 s/the forced vital capacity (FEV(1)/FVC) ratio, brachial-ankle pulse wave velocity (baPWV), blood C-reactive protein (CRP) and B-natriuretic peptide (BNP) levels were measured. The prevalence rate of COPD was 12% in this study subjects. Plasma BNP levels and the crude (median value, 17.2 vs. 14.1 m/s, p < 0.01) and adjusted value of baPWV were significantly higher in subjects with overlap syndrome than in those with OSA alone. However, parameters of nocturnal hypoxemia and serum CRP levels were similar between both groups. Thus, the overlap of COPD in patients with OSA augments increase in arterial stiffness without the exaggeration of nocturnal hypoxemia and inflammation. Even so, this augmentation may partially contribute to the increased cardiovascular risk in the overlap syndrome.

Coexistence of obstructive sleep apnoea and metabolic syndrome is independently associated with left ventricular hypertrophy and diastolic dysfunction.

PURPOSE: This study was conducted to investigate the impact of the severity of obstructive sleep apnoea (OSA) and metabolic syndrome (MS) on left ventricular (LV) hypertrophy and LV diastolic function. METHODS: Echocardiography for evaluation of LV hypertrophy (defined by relative wall thickness (RWT) and LV mass index (LVMI)) and for diastolic function (defined by the early rapid/atrial filling velocity (E/A ratio)) was performed on 660 OSA patients. RESULTS: In patients with both MS and severe OSA, LVMI and RWT were significantly higher and the E/A ratios were significantly lower compared to patients with neither MS nor severe OSA. Multivariate analysis after adjustment for other descriptive variables demonstrated that (1) coexistent MS and severe OSA was independently associated with increased LVMI and RWT and (2) severe OSA, MS and coexistence of both disorders were independently associated with a decreased E/A ratio. Significant interaction between MS and severe OSA was not observed with respect to LVMI and RWT, but was observed for the E/A ratio. CONCLUSIONS: Coexistent severe OSA and MS can exacerbate LV concentric hypertrophy. However, not only the coexistence of these two disorders, but also either severe OSA or MS can impair LV diastolic function.

Obstructive sleep apnea as a potential risk factor for aortic disease.

Obstructive sleep apnea (OSA) is not only a cause of hypertension; it also possibly affects the pathogenesis and progression of aortic disease because an inspiratory effort-induced increase in negative intrathoracic pressure generates mechanical stress on the aortic wall. The objective of the present study was to examine the incidence by location of OSA as a complication in patients with aortic aneurysm and patients with aortic dissection (AD). An overnight sleep study was conducted in the following study groups: the aortic disease group (n = 95) consisting of patients with thoracic aortic aneurysm (TAA, n = 32), patients with abdominal aortic aneurysm (AAA, n = 36), and patients with AD (n = 27); and a control group (n = 32), consisting of patients with coronary risk factors who were matched with the aortic disease group for age, gender, and body mass index (BMI). The 3% oxygen desaturation index (ODI) was significantly higher in all the TAA, AAA, and AD groups (P = 0.045, P = 0.003, and P = 0.005, respectively) than in the control group. The incidence of moderate to severe OSA [apnea hypopnea index (AHI) ≥15 events/h] was significantly higher in the first three groups (P = 0.026, P = 0.001, P = 0.003, respectively) than in the control group, while no significant difference was found between the TAA group and the AAA group with respect to these variables. Furthermore, no significant differences were found between the thoracic AD subgroup and the abdominal AD subgroup with respect to AHI and 3% ODI, as well as with respect to the incidences of moderate to severe OSA. Patients with TAA, patients with AAA, and patients with AD showed high incidences of moderate to severe OSA. Although this result suggests that OSA may be one of risks for aortic disease, unelucidated mechanism(s) other than negative intrathoracic pressure may be involved in the pathogenesis of aortic disease.

Gastric mucosal damage evaluated by transnasal endoscopy and QOL assessments in ischemic heart disease patients receiving low-dose aspirin.

OBJECTIVE: Transnasal endoscopy was conducted to examine gastric mucosal damage in Japanese patients with ischemic heart disease who were receiving low-dose aspirin for preventing the onset or recurrence of cardiovascular disease. PATIENTS AND METHODS: An endoscopist assessed gastric mucosal damage. Furthermore, the MOS 36-Item Short-Form Health Survey (SF-36(®)) and the Gastrointestinal Symptom-Rating Scale (GSRS) were used to assess the outcomes of their quality of life (QOL) and the possible presence of gastric cancer and H. pylori infection. RESULTS: Seventy-five patients were studied; and 24 (32.0%) and 16 (21.3%) of them concurrently received antithrombotic drugs other than aspirin and antiulcer drugs, respectively. Regarding gastric mucosal damage, 15 (20.0%) and 8 (10.7%) of the patients were endoscopically diagnosed with ulcer and hemorrhagic gastritis, respectively. Furthermore, 5 patients (6.7%) were found to have esophageal or gastric cancer. The positivity rate of Helicobacter pylori (H. pylori) was 45.3%. Patients receiving low-dose aspirin showed a decreased QOL. Consequently, no significant differences were found among the groups. Regarding endoscopic findings, no differences were found in the scores of both SF-36(®) and GSRS with respect to the presence or absence of gastric ulcer, hemorrhagic gastritis, and H. pylori infection. CONCLUSION: Transnasal endoscopy was possible to perform during the oral intake of low-dose aspirin without causing any hemorrhagic complications. Many patients with gastric mucosal lesions showed no subjective symptom, and patients receiving aspirin were strongly recommended to undergo regular transnasal endoscopy, regardless of the presence or absence of symptoms.

Severe obstructive sleep apnea increases cystatin C in clinically latent renal dysfunction.

BACKGROUND: Obstructive sleep apnea (OSA) increases the risk of cardiovascular disease (CVD) and has been reported to be associated with chronic kidney disease (CKD). Recent studies have demonstrated that cystatin C is a prognostic biomarker of the risk of death and CVD even in patients without established CKD. METHODS: In a cross-sectional study, we enrolled 267 consecutive OSA patients without CKD who had an apnea-hypopnea index (AHI) ≥ 5 events per hour in overnight polysomnography. CKD was defined as an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m(2) according to the modification of diet in renal disease (MDRD) equation (modified for Japanese). Serum cystatin C levels were measured in all patients. RESULTS: Cystatin C was significantly correlated with age (r = 0.37), body mass index (BMI) (r = 0.12), AHI (r = 0.17), C-reactive protein (CRP) (r = 0.12), and Brachial-ankle pulse wave velocity (r = 0.18). Logistic regression analysis demonstrated that severe OSA defined by an AHI ≥ 30 events per hour was an independent variable for the highest quartiles of serum cystatin C levels (≥0.88 mg/L) (OR: 2.04, 95% CI: 1.04-4.01, P = 0.04) even after adjustment for age, BMI ≥ 25, hypertension, and diabetes mellitus. CONCLUSIONS: This study indicates that severe OSA independently increases serum cystatin C levels in patients without CKD. Cystatin C is considered to be a biomarker that reflects both clinically latent renal dysfunction and cardiovascular risk that are influenced by OSA.

Effects of CPAP therapy on the sympathovagal balance and arterial stiffness in obstructive sleep apnea.

OBJECTIVE: Increased arterial stiffness and sympathovagal imbalance are noted in patients with obstructive sleep apnea (OSA). It has been thought that continuous positive airway pressure (CPAP) therapy can have beneficial effects on the vascular function in such cases. However, it is not yet clear whether the improvement of sympathovagal balance by CPAP might be related to reduction of the arterial stiffness, independent of changes in the blood pressure. METHODS: In 50 consecutive eligible patients with OSA (apnea-hypopnea index>/=20/hour) receiving CPAP therapy, the brachial-ankle pulse wave velocity (baPWV), heart rate variability (LF, HF and LF/HF ratio), baroreceptor sensitivity (BRS), plasma levels of C-reactive protein (CRP), and endothelial function as assessed by changes in the forearm blood flow before and after reactive hyperemia (END) were measured before and after 3-months' CPAP therapy. RESULTS: Significant decrease of the LF/HF ratio, plasma levels of CRP, baPWV and heart rate were observed after 3 months' CPAP therapy. The change in the baPWV following 3-months' CPAP therapy was significantly correlated with the change in the LF/HF ratio and mean blood pressure (MBP), but not with that of the BRS, CRP or END after the therapy. Multivariate linear regression analysis demonstrated a significant correlation between the change in the LF/HF ratio and that in the baPWV (beta=0.305, p=0.041), independent of the changes in the MBP, plasma CRP levels and heart rate. CONCLUSIONS: Improvement of the sympathovagal balance by CPAP therapy may be significantly related to decreased stiffness of the central to middle-sized arteries, independent of the changes in the blood pressure and vascular endothelial status.