Acute effects of autoadjusting and fixed continuous positive airway pressure treatments on cardiorespiratory coupling in obese patients with obstructive sleep apnea

BackgroundTreatment with positive airway pressure devices improved signs and symptoms of obstructive sleep apnea syndrome (OSA); however, auto-adjusting positive pressure (APAP) device was not as effective as continuous positive airway pressure (CPAP) in reducing arterial blood pressure and insulin resistance. The role played by autonomic cardiac regulation remains to be clarified.We aimed to test the effects of CPAP and APAP on autonomic regulation and cardiorespiratory coupling during sleep.MethodsWe retrospectively analyzed full-night polysomnographic studies. 19 patients newly diagnosed with severe OSA (AHI > 30) and 7 obese subjects without OSA (CON) were enrolled. Each OSA subject was assigned to CPAP or APAP treatment and underwent a sleep study after 1 week of treatment. Spectral and cross-spectral analyses of heart rate variability (HRV) and respiration were performed to assess autonomic profile and coherence (K²) between respiration and HF oscillation during sleep in CPAP, APAP and CON groups.ResultsIn CPAP and CON, LFnu and LF/HF, markers of sympathetic modulation, decreased from N2 to N3 and increased during REM sleep (p < 0.001), while in APAP group, sympathetic modulation was significantly higher compared with those of CPAP and CON during all sleep stages. K² values were lower in APAP compared with those in CPAP and CON.ConclusionAPAP treatment was characterized by a greater sympathetic activation and it was associated with a lower cardio-respiratory coupling compared with CPAP. This might account for the different effects on cardiovascular risk factors induced by the two treatments.     

Heart Rate Variability in Obstructive Sleep Apnea: A Prospective Study and Frequency Domain Analysis

Background: Cyclic variation of the heart rate is observed during apneic spells in obstructive sleep apnea (OSA). We hypothesized that autonomic changes would affect frequency‐domain measures of heart rate variability (HRV). Methods: We studied 20 patients (15 men, 5 women, mean age 47.2 ± 12.2 years) with suspected OSA undergoing overnight polysomnography, and five patients (4 men, 1 woman, mean age 49.2 ± 8.6 years) with recently diagnosed sleep apnea undergoing polysomnography while wearing continuous positive airway pressure (CPAP). Holter monitors were applied during sleep studies and data were analyzed in 5‐minute blocks over the course of the night. Using spectral analysis, low frequency (LF) and high frequency (HF) powers were calculated for each interval. Overall mean and standard deviation (SD) for LF power, HF power, and the LF:HF ratio were recorded for each patient. Comparisons were made between patients with severe OSA (apnea hypopnea index (AHI) > 30, n = 8 ), moderate OSA (AHI 1–30, n = 5 ), without OSA (AHI < 10, n = 7 ), and patients wearing CPAP (n = 5 ). Results: Assessment of overnight LF or HF power revealed no significant difference between the four groups. The LF:HF ratio, which represents sympathovagal balance, was higher among those with moderate disease compared to normals and those with severe OSA (both P = 0.037 ). The standard deviation of the LF:HF ratio was higher among those with moderate disease compared to normals (P = 0.0064) and those with severe OSA (P = 0.0006) . OSA patients receiving CPAP behaved like patients with moderate OSA, with increased SD of the LF:HF ratio. Conclusions: The observed changes in the LF:HF ratio and its SD suggest an increased sympathetic tone and discordance in sympathovagal activity in moderate OSA, which is blunted in severe OSA. CPAP may restore autonomic defects, characteristic of severe OSA, to moderate levels.     

The impact of continuous positive airway pressure on heart rate variability in obstructive sleep apnea patients during sleep: A meta-analysis

Background

Heart rate variability (HRV), modulated by cardiac autonomic function, is impaired in obstructive sleep apnea (OSA). However, the effect of continuous positive airway pressure (CPAP) on HRV is debated.

Efficacy and patient satisfaction with autoadjusting CPAP with variable expiratory pressure vs standard CPAP: a two-night randomized crossover trial

Expiratory pressure relief (C-Flex) technology monitors the patient’s airflow during expiration and reduces the pressure in response to the patient. Increased comfort levels associated with C-Flex therapy have potential to improve patient adherence to therapy. The purpose of this study was to assess the combination of autoadjusting CPAP (APAP) and C-Flex in terms of (1) treatment efficacy, and (2) patient preference when compared to standard CPAP. Fifteen patients who had previously undergone formal CPAP titration polysomnography were treated with either one night of the APAP with C-Flex or one night of conventional CPAP, in a crossover trial. Patient satisfaction levels were recorded using visual analog scales (VAS) on the morning after the study. Mean patient age was 50 ± 12 years, body mass index (BMI) was 36 ± 6 kg/m², baseline AHI was 53 ± 31 events/h, and CPAP Pressure was 11 ± 2 cm/H₂O. APAP with C-Flex was as effective as CPAP, with no differences detected in sleep latency (17 ± 5 vs 12.3 ± 3 min, p = 0.4), or respiratory indices (AHI of 4.2 ± 2 vs 2.4 ± 0.7 events/h, p = 0.1). VAS scores (scale 0–10) indicated a trend towards increased patient satisfaction while using APAP with C-Flex (7.9 vs 7.2, p = 0.07). 10 patients expressed a preference for APAP with C-Flex (VAS, 0 to10) over standard CPAP (total positive score of 68, mean score of 4.8 ± 4.3). One patient expressed no preference. Four patients expressed a preference for CPAP (total positive score of 13, mean score of 0.9 ± 1.9) (APAP with C-Flex vs standard CPAP, p < 0.01 paired t test). APAP with C-Flex eliminates sleep disordered breathing as effectively as standard CPAP. Patients indicated a preference for APAP with C-Flex suggesting a possible advantage in terms of patient adherence for this mode of treatment.     

Automatic pressure titration with APAP is as effective as manual titration with CPAP in patients with obstructive sleep apnea

BACKGROUND: The optimal approach to initiate positive-pressure therapy in patients with obstructive sleep apnea is still debated. Current options are autotitrating positive airway pressure (APAP) or manual titration with continuous positive airway pressure (CPAP). Procedures differ by parameters and by algorithms used for adapting pressure. OBJECTIVES: To evaluate the efficacy of attended automatic titration in a randomized crossover study compared with manual titration over 2 nights where the sequence of the titration mode was changed. Therapy outcome was controlled after 6 weeks. METHODS: 21 sleep apnea patients were treated using manual CPAP versus automatic APAP titration. The mode used during the 2nd night was continued for 6 weeks. Cardiorespiratory polysomnography, Epworth Sleepiness Scale (ESS), SF-36 score and compliance were assessed. RESULTS: Apnea-hypopnea index reduction was equally effective at similar effective pressure independent of the titration mode. If APAP was applied during the 1st night, total sleep time was longer (384 vs. 331 min, p < 0.01) and sleep efficacy was higher (91 vs. 81%, p < 0.01) than after starting with manual titration with CPAP. Compliance was comparable in both groups (4.6 +/- 1.9 h). The ESS improved in both groups (from 12.9 to 6.5). SF-36 scores and therapeutic pressure did not much change. CONCLUSIONS: Taking the sequence of titration into account, we found equal effectiveness of CPAP and APAP. Sleep quality was better with initial application of APAP - which favors attended automatic titration if only 1 titration night is possible. Both modes are comparable after 6 weeks regarding therapeutic pressure, efficacy, compliance and quality of life.     

The role of telemedicine in CPAP compliance for patients with obstructive sleep apnea syndrome

The objective of this study was to compare continuous positive airway pressure (CPAP) use, functional status, and client satisfaction in obstructive sleep apnea syndrome (OSAS) patients randomized to either telemedicine support or traditional care. In our university-affiliated sleep disorders center, patients with OSAS who were initiating CPAP therapy were randomized to receive telemedicine support vs traditional follow-up care for 30 days. The telemedicine group received a “Health Buddy” computer that provided daily Internet-based informational support and feedback for problems experienced with CPAP use. At 30 days, there were no significant differences in the hours of CPAP use between groups receiving traditional care (M=4.22, SD±2.05) and telemedicine support (M=4.29, SD±2.15), p=0.87, or in the proportion of nights with CPAP use between the traditional (M=50%±33.8) and telemedicine groups (M=47%±34.2), p=0.61. No significant differences were found between groups in functional status (M=2.27±4.56 vs M=2.03±3.88, respectively, p=0.76) or client satisfaction (M=28.0±3.51 vs M=28.5±3.05, p=0.43). Patients in the telemedicine and traditional groups had similar CPAP use, functional status, and client satisfaction. The data suggest that telemedicine support as provided by our model compares favorably with traditional care. As a provider-extender, telemedicine support for patients initiating use of CPAP may allow for greater practice efficiency while maintaining quality of care. Disclosure Statement: Supported by the Telemedicine Directorate, Walter Reed Army Medical Center, Washington, DC.     

Autotitration positive airway pressure therapy in patients with obstructive sleep apnea who are intolerant of fixed continuous positive airway pressure

Compliance with continuous positive airway pressure (CPAP) therapy is one of the most difficult management problems for patients with obstructive sleep apnea (OSA). We postulated that autotitration positive airway pressure (APAP) may be effective in some patients who have an intolerance of fixed CPAP. The study was done to estimate how often patients who cannot tolerate fixed CPAP can tolerate APAP. We identified 25 patients seen in the Sleep Disorders Center who had been treated with fixed CPAP for OSA and were intolerant of CPAP therapy despite multiple efforts to improve tolerance. We substituted APAP therapy and measured subjective and objective compliance with treatment 1 month later. The primary end point was the number of patients who successfully tolerated the use of APAP at the end of 30 days, measured objectively by the device's compliance monitor. A positive outcome was defined as an average use of APAP that was greater than 3 h per night on more than 70% of possible nights. Of the 25 patients (mean age, 68 years; mean apnea-hypopnea index, 35), 11 were able to tolerate APAP therapy. The mean number of hours of use in these responders was 6.2; the mean percentage of nights of use among responders was 89%. Determinants of successful APAP use were an apnea-hypopnea index (AHI) less than 18, male sex, OSA related to rapid eye movement, and a high body mass index. APAP therapy may be an effective option in patients who do not tolerate fixed-CPAP therapy.     

CPAP Compliance in Sleep Apnea Patients with and without Laboratory CPAP Titration

Advances in auto-adjusting positive airway pressure technology for obstructive sleep apnea now permit this treatment to be initiated outside of the sleep laboratory environment, bypassing the need for laboratory-based titration studies. Thus far, little research has addressed how such developments may affect compliance to continuous positive airway pressure (CPAP). We tested the effect of laboratory CPAP exposure and technologist support in a retrospective chart review of 98 veterans with obstructive sleep apnea to determine whether patients who received standard laboratory CPAP titration complied better with CPAP than did patients who received no laboratory CPAP titration. Fifty patients underwent standard technician-attended polysomnography (PSG) with CPAP titration, and 48 patients underwent unattended PSG with no laboratory trial of CPAP (first CPAP exposure was at home). Objective CPAP compliance measures were obtained from CPAP units at follow-up visits. Attended-PSG patients wore CPAP significantly longer per night on average (5.0 hours vs 3.9 hours) and tended to wear CPAP on more nights (76.5% vs 64.2%) compared with unattended-PSG patients. These findings suggest that patients sleep laboratory experience with CPAP and the support and education provided by sleep technologists are important factors in facilitating CPAP compliance.     

Randomised trial of compliance with flexible (C-Flex) and standard continuous positive airway pressure for severe obstructive sleep apnea

Introduction  Obstructive sleep apnea (OSA) is often treated with continuous positive airway pressure (CPAP) but the effectiveness of treatment is probably limited by poor compliance. CPAP manufacturers are thus attempting to devise more comfortable PAP devices in an effort to improve compliance. An example of such a novel device is Flexible expiratory-modulated PAP (C-Flex mode Respironics REMstar Pro, Murraysville, PA, USA). Materials and methods  We aimed to compare compliance between C-Flex and standard CPAP in patients with severe OSA in a randomised controlled trial. Nineteen patients with severe OSA (mean ± SD Apnea Hypopnea Index = 78 ± 33/h, Epworth 14 ± 4, PAP 8–17 cm H₂O, BMI = 39 ± 10 kg/m²) and aged 20–63 years were randomly assigned to 4 weeks of either C-Flex (setting II, n = 9) or CPAP (n = 10). Results  Patients treated with C-Flex exhibited a trend toward higher compliance with their PAP devices compared to patients treated with standard CPAP (4.7 ± 2.9 vs. 3.0 ± 2.1 h/night, p = 0.15, effect size = 0.68). Paradoxically, improvements in subjective sleepiness (Epworth Sleepiness Scale) were greater in those who received CPAP than C-Flex (8.1 + 4.9 vs. 2.1 + 4.0 points, p = 0.014, effect size = 1.46). Improvements in objective wakefulness (Modified Maintenance of Wakefulness Test) and simple reaction times (Psychomotor Vigilance Task) were not significantly different between treatments. This randomised trial provides some evidence that C-Flex might increase initial treatment compliance, compared to CPAP, in patients with severe OSA. However, this trend toward greater compliance was not associated with better short-term treatment outcomes for patients. These findings need to be confirmed in a larger, longer-term trial. Stipend from Massey University (to NSM). None of the authors have had any financial relationships with Respironics Inc., who are the manufacturers of the device tested. Respironics International Inc., through their New Zealand suppliers Care Medical, provided six C-Flex machines for the purposes of this trial.     

Longitudinal comparison study of pressure relief (C-Flex?) vs. CPAP in OSA patients

Background  Continuous positive airway pressure (CPAP) devices with the option of flexible pressure delivery (e.g., C-Flex) are thought to provide an improved degree of comfort and result in better therapeutic adherence while maintaining standard CPAP efficacy. The purpose of this study was to compare adherence and subjective measures of comfort between C-Flex and CPAP treatment. Methods  The study was an international, multisite, single-blinded study with participants randomized to either C-Flex or CPAP. Participants completed subjective measures of sleepiness and comfort at baseline, and at 30-, 90-, and 180-day follow-ups. Additionally, compliance data were downloaded from the device at each follow-up. Repeated measures analysis of variance was used to assess the effects of treatment. Results  There were 138 men and 46 women (average age of 48 ± 9.2, average Epworth Sleepiness Scale score of 14.9 ± 3.6, and average diagnostic apnea/hypopnea index (AHI) of 51.9 ± 27.7). C-Flex and CPAP groups were comparable on baseline measures, achieved comparable AHI on titration, and had comparable PAP pressure requirements. C-Flex users had comparable average hours of use per night and total nights of use across the study, but had a trend (p < .07) toward achieving greater total hours of utilization. While both groups had comparable decreases in sleepiness, C-Flex users reported on visual analog scales greater comfort (64.3 vs. 57.4; p = .01). Conclusions  The results of this study demonstrated that C-Flex has comparable resolution of respiratory indices and adherence. Furthermore, C-Flex users reported greater mask comfort.     

Effects of Nasal CPAP Treatment on Insulin Resistance, Lipid Profile, and Plasma Leptin in Sleep Apnea

Background  Obstructive sleep apnea has been linked with metabolic syndrome characterized by dyslipidemia, dyscoagulation, hypertension, and diabetes mellitus type 2 and their cardiovascular consequences. This study was designed to determine the effects of 8 weeks of therapy with continuous positive airway pressure (CPAP) on insulin resistance, glucose, and lipid profile, and the relationship between leptin and insulin-resistance parameters in patients with moderate-to-severe obstructive sleep apnea. Methods  In 44 patients, serum cholesterol, triglycerides, high-density lipoprotein, low-density lipoprotein, very low-density lipoprotein, leptin, and insulin parameters were measured at baseline and after 8 weeks of CPAP. Insulin resistance index was based on the homeostasis model assessment (HOMA-IR) method. Insulin sensitivity (HOMA-S) and insulin secretion capacity (HOMA-β) also were calculated. Thirteen patients were excluded from statistical analyses due to noncompliant CPAP usage (<4 h night⁻¹). Results  In 31 patients who used CPAP for ≥4 h night⁻¹, CPAP therapy reduced total cholesterol (P < 0.05), low-density lipoprotein (P < 0.05), and leptin (P < 0.05). Circulating leptin levels showed significant correlation with both HOMA-S and HOMA-IR at baseline and follow-up (P = 0.03 for all). In addition, there was no correlation between HOMA-IR and the severity of sleep apnea, which was shown by apnea-hypopnea index. Conclusions  In patients with moderate-to-severe obstructive sleep apnea, compliant CPAP usage may improve insulin secretion capacity, reduce leptin, total cholesterol, and low-density lipoprotein levels. Leptin showed significant relationship with insulin resistance, and this relationship remained after 8 weeks of CPAP therapy.     

Short- and long-term effects of CPAP on upper airway anatomy and collapsibility in OSAH

Rationale and aim  In obstructive sleep apnea hypopnea (OSAH) patients, an increase of upper airway (UA) collapsibility has been described together with a reduced UA caliber due to inflammation, edema, and fat accumulation in pharyngeal walls. CPAP is the main treatment of OSAH and acts mechanically by increasing pressure inside UA. The aim of this study was to assess the short- and long-term effects of CPAP on UA caliber and collapsibility in severe OSAH patients. Patients and methods  Ten obese patients (nine male, age 55± 9 yr, BMI 35.1 ± 6.1, Epworth sleepiness scale 12.3 ± 3.6 point, AHI 58.8 ± 27.1) had measurements of oropharingeal junction area (OPJ), mean pharyngeal area (APmean), maximal pharyngeal area (APmax) by acoustic pharyngometry and determination of expired volume in the first 0.5 s after the application at the mouth of −5 cmH₂O negative expiratory pressure (V,NEP_0.5) during wakefulness in the supine position under basal conditions (baseline) and after 1 week and 6 months of CPAP treatment. Results  OPJ was 0.74 ± 0.28 cm² at baseline, 0.90 ± 0.24 cm² after 1 week and 1.05 ± 0.31 cm² after 6 months (1 week and 6 months vs baseline p < 0.05). APmax was 2.28 ± 0.74 cm² at baseline, 2.79 ± 0.90 cm² after 1 week and 2.94 ± 0.33 cm² after 6 months (1 week and 6 months vs baseline p < 0.05). APmean was 1.43 ± 0.46 cm² at baseline, 1.82 ± 0.45 cm² after 1 week and 1.94 ± 0.35 cm² after 6 months (1 week vs baseline p < 0.01; 6 months vs baseline; p < 0.05). V,NEP_0.5 was 290 ± 73 mL at baseline, 291 ± 65 mL after 1 week and 338 ± 67 mL after 6 months (6 months vs baseline p < 0.05; 1 week vs 6 months p < 0.01). Conclusions  Our data suggest that CPAP treatment might be effective in OSAH patients not only by causing a mechanical splint of UA but also by inducing an improvement on anatomical (early) and functional (later on) aspects of UA that can be observed during wakefulness.     

阻塞性睡眠呼吸暂停患者持续正压通气治疗前后自主神经 …

目的 研究阻塞性睡眠呼吸暂停（ＯＳＡ）患者夜间睡眠时自主神经功能的状态，以及有效的持续正压通气治疗对自主神经张力的影响。方法 对５６例重度ＯＳＡ患者持续正压通气（ＣＰＡＰ）治疗前和治疗中进行夜间７小时多导睡眠图（ＰＳＧ）及动态心电图监测，另择３０名正常受试者作为对照。采用心率功率谱分析法（ＨＲＰＳＡ）定量分析ＯＳＡ患者治疗前后夜间自主神经功能的变化。结果 ＯＳＡ组夜间睡眠时伴随着反复的呼吸暂停和低     

Gabapentin therapy improves heart rate variability in diabetic patients with peripheral neuropathy

PurposeDiabetic cardiac neuropathy, which is characterized by reduced heart rate variability (HRV), frequently coexists with peripheral neuropathy. Gabapentin has been used for the treatment of diabetic neuropathy. We aimed to evaluate the possible effect of gabapentin treatment on autonomic function in patients with type 2 diabetes via HRV.MethodsThirty patients with type 2 diabetes mellitus and peripheral neuropathy and 28 age- and sex-matched healthy controls were consecutively registered. Each patient underwent HRV measurements, and diabetic patients were administered gabapentin. After 3 months of gabapentin therapy, HRV parameters were measured again.ResultsBaseline HRV parameters were blunted in patients with diabetes mellitus according to the controls [standard deviation of all NN intervals (SDNN, ms): 106.3±29.9 vs. 148.8±36.5, P=.001; power spectrum of the high-frequency band (HF, ms²): 133.6±98.3 to 231.4±197.6, P=.02; power spectrum of the low-frequency band (LF, ms²): 341.8±247.8 to 511.5±409.4, P=.048; LF/HF ratio: 3.3±2.4 to 2.6±1.5, P=.33]. After 3 months of treatment with gabapentin, some HRV parameters showed some improvement. SDNN (106.2±29.8 to 119.4 ± 25, P=.016) and HF (133.6±98.3 to 167.6±118.3, P=.021) increased significantly. LF/HF ratio decreased (from 3.3±2.4 to 2.3±1.9, P=.039) and LF remained unchanged (341.8±247.8 to 352.3±228.9, P=.88).ConclusionsTherapeutic doses of gabapentin not only alleviate neuropathic symptoms but also improve cardiac autonomic function in diabetic patients with peripheral neuropathy.     

Initiation of therapy for obstructive sleep apnea syndrome: a randomized comparison of outcomes of telemetry-supported home-based vs. sleep lab-based therapy initiation

Purpose

Diagnosis and treatment of obstructive sleep apnea are traditionally performed in sleep laboratories with polysomnography (PSG) and are associated with significant waiting times for patients and high cost. We investigated if initiation of auto-titrating CPAP (APAP) treatment at home in patients with obstructive sleep apnea (OSA) and subsequent telemonitoring by a homecare provider would be non-inferior to in-lab management with diagnostic PSG, subsequent in-lab APAP initiation, and standard follow-up regarding compliance and disease-specific quality of life.

Methods

This randomized, open-label, single-center study was conducted in Germany. Screening occurred between December 2013 and November 2015. Eligible patients with moderate-to-severe OSA documented by polygraphy (PG) were randomized to home management or standard care. All patients were managed by certified sleep physicians. The home management group received APAP therapy at home, followed by telemonitoring. The control group received a diagnostic PSG, followed by therapy initiation in the sleep laboratory. The primary endpoint was therapy compliance, measured as average APAP usage after 6 months.

Results

The intention-to-treat population (ITT) included 224 patients (110 home therapy, 114 controls); the per-protocol population (PP) included 182 patients with 6-month device usage data (89 home therapy, 93 controls). In the PP analysis, mean APAP usage at 6 months was not different in the home therapy and control groups (4.38 ± 2.04 vs. 4.32 ± 2.28, p = 0.845). The pre-specified non-inferiority margin (NIM) of 0.3 h/day was not achieved (p = 0.130); statistical significance was achieved in a post hoc analysis when NIM was set at 0.5 h/day (p < 0.05). Time to APAP initiation was significantly shorter in the home therapy group (7.6 ± 7.2 vs. 46.1 ± 23.8 days; p < 0.0001).

Conclusion

Use of a home-based telemonitoring strategy for initiation of APAP in selected patients with OSA managed by sleep physicians is feasible, appears to be non-inferior to standard sleep laboratory procedures, and facilitates faster access to therapy.

     

Continuous positive airway pressure in heart failure patients with obstructive sleep apnoea

Background: The aim of the study was to study the effect of 6 months of continuous positive airway pressure (CPAP) in community heart failure (HF) patients with obstructive sleep apnoea (OSA). Methods: Clinically stable outpatients with HF and OSA (left ventricular ejection fraction (LVEF) <45%, apnoea/hypopnoea index >15/h, n = 19) treated with CPAP and a control group (LVEF <45%, apnoea/hypopnoea index <10/h, n = 7) were compared at baseline and at 6 months by Minnesota heart failure score, Epworth sleepiness score, shuttle walk distance, brain natriuretic peptide, urinary catecholamines and echocardiographic indices using paired t‐test, McNemar’s tests and effect sizes. Results: In HF patients with OSA, CPAP improved LVEF (35.9 ± 6.1% to 40.6 ± 8.0%, P = 0.015), decreased LV end‐systolic volume (152 ± 74 to 135 ± 62 cm³, P = 0.03), systolic blood pressure (P = 0.04) and sleepiness (Epworth sleepiness score 8.8 ± 4.8 to 6.3 ± 3.2, P = 0.01), whereas walk distance, catecholamines, brain natriuretic peptide levels and symptoms were unchanged. These outcomes did not change in the HF control group. Conclusion: In community HF patients with OSA, CPAP therapy over 6 months improved LVEF, systolic blood pressure and sleepiness, but not sympathetic activation, brain natriuretic peptide or exercise levels. Acceptance was relatively low, potentially limiting therapeutic effectiveness.     

Effect of pioglitazone on cardiac sympathovagal modulation in patients with type 2 diabetes

This study aims to examine the effect of pioglitazone on potential progression of autonomic damage in addition to changes in control of cardiovascular function in patients with type 2 diabetes (T2DM). Thirty patients with T2DM and 32 healthy subjects participated in the study. Sympathovagal activity, assessed by power spectral analysis (PSA) of R–R intervals variability, and blood pressure (BP) were studied during clinostatism and orthostatism in controls and patients. We have assessed blood pressure control by 24-hour monitoring of ambulatory blood pressure. Patients were treated with pioglitazone (30 mg/day) for 6 months, and then re-evaluated by PSA for heart rate variability (HRV). Reduced levels of HbA1c (P < 0.0001) and urinary albumin (P = 0.008) were observed in pioglitazone-treated patients compared to untreated baseline levels. Arterial BP remained unchanged following pioglitazone treatment. T2DM patients had reduced HRV (low-frequency power; LF; P < 0.0001 and LF/HF; LF/HF; P < 0.0001) at baseline (clinostatism) compared to controls. Baseline clinostatic differences between groups persisted after pioglitazone treatment and no effect of treatment on basal HRV variables was observed. In controls, HF decreased and LF and LF/HF ratio increased in the orthostatic position. A similar effect for HF was observed in patients, but LF and LF/HF did not increase. The normal difference between HF-power in clinostatism versus orthostatism observed for controls (P < 0.0001) was restored in patients following pioglitazone treatment (P = 0.028). A significant decrease from lying to standing position in orthostatic LF-power (P < 0.0001) and LF/HF (P < 0.0001) was also observed between patients and controls. Although no differences in autonomic control of HRV were observed between controls and patients with T2DM, significant differences were observed in sympathovagal balance following either clinostatic or orthostatic challenge. These findings provide initial evidence of a potential additional benefit afforded by pioglitazone for the improvement of cardiac sympathovagal balance in T2DM.     

Nasal nitric oxide improved by continuous positive airway pressure therapy for upper airway inflammation in obstructive sleep apnea

Purpose

In this report, we examined the association between obstructive sleep apnea (OSA) and upper and lower airway inflammation based on nitric oxide (NO) measurements.

Methods

Study subjects included 51 consecutive participants. Sleep-disordered breathing was evaluated by a type 3 portable monitor and quantified by respiratory disturbance index (RDI). Airway inflammation was noninvasively analyzed by the measurement of nasally and orally exhaled NO; nasal value was presented as nasally exhaled NO minus orally exhaled NO. In 15 patients prescribed nasal continuous positive airway pressure (nCPAP) therapy, exhaled NO was re-evaluated in 10.7 ± 6.3 months after nCPAP therapy.

Results

Nasal NO was significantly higher in patients with severe OSA (RDI ≥ 30/h) than those with non-OSA (RDI < 10/h) (76.9 ± 26.0 ppb vs. 47.9 ± 22.0 ppb, respectively, p = 0.016) and correlated with RDI (rho = 0.36, p = 0.0099), whereas orally exhaled NO did not differ between non-OSA and OSA patients and was not correlated with RDI. In 15 patients, nasal NO after nCPAP therapy was significantly decreased than that before nCPAP therapy (81.9 ± 31.2 ppb vs. 53.7 ± 27.2 ppb, respectively, p = 0.0046); in 11 patients having good compliance to nCPAP therapy (nCPAP use >4 h per night on more than 70% of nights), this association was more remarkable.

Conclusions

In OSA, upper but not lower airway inflammation can be increased by repetitive collapse of the upper airway. Future studies are required to determine the role of nasal NO in OSA.

     

Short-term effects of oral theophylline in addition to CPAP in mild to moderate OSAS

Theophylline is effective in the treatment of central apneas and periodic breathing. In obstructive sleep apnea syndrome (OSAS), results of pharmacological monotherapy with theophylline are inconsistent. The present study investigates whether additional theophylline in patients with OSAS and continuous positive airway pressure (CPAP) therapy might improve ventilation, lower effective CPAP pressure levels or affect sleep architecture. Patients with mild to moderate OSAS (mean apnea index [AI] 12.8+/-11.7) and CPAP therapy (Autoset system; n=16, all male) received either 900 mg of oral sustained-release theophylline (T) or placebo (P) on two separate nights, 3 days apart, using a randomized double-blind crossover study design. There was no change in AI (T: 0.7+/-1.4 vs. P: 0.7+/-0.6/h; P=0.3) or apnea-hypopnea index (AHI; T: 4.3+/-3.3 vs. P: 4.5+/-3.7/h; P=0.84) when theophylline was added to CPAP therapy. We observed no difference in mean CPAP pressure (T: 6.9+/-2.1 vs. P: 6.7+/-1.9 cm H2O; P=0.7) or 95% pressure percentiles (T: 9.7+/-2.7 vs. P: 9.3+/-2.1cm H2O; P=0.3) when nights with theophylline were compared to placebo nights. Theophylline reduced significantly total sleep time (T: 290.6+/-58.9 vs. P: 338.0+/-40.1 min; P=0.02) and thus sleep efficiency (SE; T: 70.5+/-14.9%, P: 82.0+/-70.5%; P=0.005). Rapid eye movement and slow wave sleep were not affected. Oral theophylline did not show any additional effects on ventilation parameters or pressures in patients with mild to moderate OSAS once CPAP therapy has been successfully installed. SE was reduced with theophylline with unchanged sleep architecture. The role of oral theophylline may be in patients with predominately central apneas not eligible for ventilation therapy or severe cases.     

The effect of continuous positive airway pressure on glucose control in diabetic patients with severe obstructive sleep apnea

Obstructive sleep apnea (OSA) is independently associated with glucose intolerance and insulin resistance, and recent studies have shown that continuous positive airway pressure (CPAP) improves insulin sensitivity. The objective of this study was to describe the change in glycosylated hemoglobin (HbA1c) after treatment with CPAP in patients with type 2 diabetes mellitus and OSA. To test this hypothesis, we performed a retrospective analysis of 38 patients seen in the sleep clinic of an urban public teaching hospital. All patients had OSA and type 2 diabetes mellitus, and their diabetic medication regimen had remained unchanged during the period of CPAP therapy. Sixty-one percent were men, body mass index was 42±9.5 kg/m², and the Apnea–Hypopnea Index was 53±36 per hour. HbA1c before therapy with CPAP was 7.8±1.4% and decreased to 7.3±1.3% after 134±119 days of therapy (p<0.001). Treatment with CPAP leads to a clinically significant drop in HbA1c in patients with type 2 diabetes mellitus and severe OSA.