The effects of 1-year treatment with a herbst mandibular advancement splint on obstructive sleep apnea, oxidative stress, and endothelial function

Technion - Israel Institute of Technology, H̱efa, Haifa, Israel
Chest (Impact Factor: 7.13). 03/2007; 131(3):740-9. DOI: 10.1378/chest.06-0965
Source: PubMed

ABSTRACT Obstructive sleep apnea (OSA) is associated with endothelial dysfunction. In the current study, we assessed the effect of long-term modified Herbst mandibular advancement splint (MAS) treatment on OSA, oxidative stress markers, and on endothelial function (EF).
A total of 16 subjects participated (11 men and 5 women; mean [+/- SD] age, 54.0 +/- 8.3 years; mean body mass index, 28.0 +/- 3.1 kg/m(2)), 12 of whom completed the 1-year evaluation. Apnea severity, levels of oxidative stress markers, and EF were assessed after 3 months and 1 year of receiving treatment. For comparison, 6 untreated patients underwent two evaluations 9 months apart, and 10 non-OSA individuals were assessed once as a reference group. The results are presented as the mean +/- SD.
The mean apnea-hypopnea index (AHI) decreased significantly from 29.7 +/- 18.5 events/h before treatment to 17.7 +/- 11.1 events/h after 3 months of treatment and 19.6 +/- 11.5 events/h after 1 year of treatment (p < 0.005 for both). The mean Epworth sleepiness scale score decreased significantly from 12.4 +/- 6.0 before treatment to 10.2 +/- 6.6 after 3 months of treatment and 7.8 +/- 3.8 after 1 year of treatment (p < 0.001 for both). The mean EF improved significantly from 1.77 +/- 0.4 before treatment to 2.1 +/- 0.4 after 3 months of treatment (p < 0.05) and 2.0 +/- 0.3 after 1 year of treatment (p = 0.055), which were similar to the values of the reference group. Thiobarbituric acid-reactive substance (TBARS) levels decreased from 18.8 +/- 6.2 nmol malondialdehyde (MDA)/mL before treatment to 15.8 +/- 3.9 MDA/mL after 3 months of treatment (p = 0.09) and 15.5 +/- 3.2 nmol MDA/mL after 1 year of treatment (p < 0.05). There was a correlation between the improvement in AHI and in EF or TBARS levels (r = 0.55; p = 0.05). The untreated control group remained unchanged.
The Herbst MAS may be a moderately effective long-term treatment for patients with OSA. EF improved to levels that were not significantly different than reference levels, even though apneic events were not completely eliminated. We think that these data are encouraging and that they justify the performance of larger randomized controlled studies.

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    • "The determination of the sample size was based on published data on the beneficial effect of an oral appliance using the same endpoint [28], showing that PAT improved from 1.77 ± 0.4 at baseline to 2.0 ± 0.4 after treatment. We hypothesized that the beneficial effect of statin treatment would be similar. "
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    ABSTRACT: Rationale. Accumulated evidence implicates sympathetic activation as inducing oxidative stress and systemic inflammation, which in turn lead to hypertension, endothelial dysfunction, and atherosclerosis in obstructive sleep apnea (OSA). Statins through their pleiotropic properties may modify inflammation, lipid profile, and cardiovascular outcomes in OSA. Methods. This multicenter, randomized, double-blind study compared the effects of atorvastatin 40 mg/day versus placebo over 12 weeks on endothelial function (the primary endpoint) measured by peripheral arterial tone (PAT). Secondary endpoints included office blood pressure (BP), early carotid atherosclerosis, arterial stiffness measured by pulse wave velocity (PWV), and metabolic parameters. Results. 51 severe OSA patients were randomized. Key demographics for the study population were age 54 ± 11 years, 21.6% female, and BMI 28.5 ± 4.5 kg/m(2). In intention to treat analysis, mean PAT difference between atorvastatin and placebo groups was 0.008 (-0.29; 0.28), P = 0.979. Total and LDL cholesterol significantly improved with atorvastatin. Systolic BP significantly decreased with atorvastatin (mean difference: -6.34 mmHg (-12.68; -0.01), P = 0.050) whereas carotid atherosclerosis and PWV were unchanged compared to the placebo group. Conclusion. In OSA patients, 3 months of atorvastatin neither improved endothelial function nor reduced early signs of atherosclerosis although it lowered blood pressure and improved lipid profile. This trial is registered with NCT00669695.
    Mediators of Inflammation 08/2014; 2014:423120. DOI:10.1155/2014/423120
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    • "Additionally, the presence of obesity and OSA contribute to the magnitude of ED lending support to the concept that both conditions may adversely impose incremental long-term cardiovascular risk [12] [13] [14]. In addition, some of the variance in endothelial function (EF) has been ascribed to circulating endothelial progenitor cells [15], and abnormalities in postocclusive reperfusion responses are reversed when adequate and effective treatment of the underlying OSA syndrome is administered [11] [16]. "
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    ABSTRACT: BACKGROUND: Restorative sleep is expected to promote improved endothelial function (EF) in the morning compared to the evening. However, in adults with obstructive sleep apnea (OSA) EF is not only adversely affected, but it worsens during the night. Data in pediatric OSA are scarce, and overnight changes have not been explored. Therefore, we sought to examine potential associations between pediatric OSA and overnight changes in EF. METHODS: 59 habitually snoring children with various degrees of sleep-disordered breathing (age range, 4-16years) underwent EF assessment (reactive hyperemia test by EndoPAT, Itamar Medical, Israel) in the evening before and the morning after an overnight polysomnography (PSG). Two brachial occlusion periods (1min and 5min) also were tested. Potential associations between evening-to-morning changes in EF and polysomnographic parameters were explored. RESULTS: Evening-to-morning changes in children with OSA displayed severity-dependent deterioration of EF, and occlusions lasting 1 or 5min during the reactive hyperemia test yielded similar findings. CONCLUSIONS: In children deterioration in EF during the night significantly correlated with the severity of OSA. Furthermore, the reactive hyperemia test can be reliably performed with only 60 seconds of arterial flow occlusion in children. These findings support our hypothesis that similarly to adults, sleep apnea in children results in endothelial dysfunction (ED). We speculate that pediatric OSA is less commonly associated with cardiovascular complications possibly due to the shorter duration of the syndrome.
    Sleep Medicine 05/2013; 14(6). DOI:10.1016/j.sleep.2013.02.010
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    • "OA is usually indicated for the treatment of patients with mild to moderate OSAS; however, it does have some disadvantages, such as inconvenience and complications (Epstein et al., 2009; Randerath et al., 2011). Itzhaki et al. (2007) reported that long-term OA treatment may improve OSAS with cardiovascular risk factors such as endothelial function and oxidative stress markers. In a recent study evaluating the effect of OA treatment for OSAS on cardiovascular autonomic variability, Coruzzi et al. (2006) concluded that 3 months of therapy using OA may improve indices related to cardiac autonomic modulation in patients with OSAS of mild degree. "
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    ABSTRACT: To determine whether surgery influences cardiovascular autonomic modulation in obstructive sleep apnoea syndrome (OSAS), the present study was performed to evaluate the effect of upper airway (UA) surgery on heart rate variability (HRV) using frequency domain analysis for patient groups who have had either successful or unsuccessful surgery. We compared body mass index (BMI), polysomnographic [apnoea index (AI), apnoea-hypopnoea index (AHI), minimum SaO(2)] and HRV [very low frequency (VLF) power, low frequency (LF) power, high frequency (HF) power, HF/LF ratio, LFnu = LF/(LF + HF), HFnu = HF/(LF + HF)] parameters between the unsuccessful (n = 14) and successful (n = 22) surgical groups before and after UA surgery. Significant changes were observed for the successful patient group with respect to mean AI (from 29.1 ± 21.3 to 2.0 ± 3.2 events h(-1), P < 0.001), AHI (from 38.6 ± 20.0 to 5.6 ± 5.1 events h(-1), P < 0.001), minimum SaO(2) (from 73.3 ± 12.7 to 86.3 ± 6.5%, P < 0.001), VLF power (from 25599 ± 12906 to 20014 ± 9839 ms(2), P = 0.013), LF power (from 17293 ± 7278 to 14155 ± 4980 ms(2), P = 0.016), LFnu (from 0.700 ± 0.104 to 0.646 ± 0.128, P = 0.031) and HFnu (from 0.300 ± 0.104 to 0.354 ± 0.128, P = 0.031); however, mean BMI, HF power and LF/HF ratio did not change significantly after UA surgery. No significant changes were observed in the unsuccessful surgical group. Successful UA surgery may improve cardiac sympathetic and parasympathetic modulation in patients with OSAS.
    Journal of Sleep Research 10/2011; 21(3):316-21. DOI:10.1111/j.1365-2869.2011.00978.x