Itzhaki, S., Dorchin, H., Clark, G., Lavie, L., Lavie, P. & Pillar, G. The effects of 1-year treatment with a Herbst mandibular advancement splint on obstructive sleep apnea, oxidative stress, and endothelial function. Chest 131, 740-749
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.
"The determination of the sample size was based on published data on the beneficial effect of an oral appliance using the same endpoint , 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. "
[Show abstract][Hide abstract] 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.
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.
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.
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(5):423120. DOI:10.1155/2014/423120 · 3.24 Impact Factor
"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   . In addition, some of the variance in endothelial function (EF) has been ascribed to circulating endothelial progenitor cells , and abnormalities in postocclusive reperfusion responses are reversed when adequate and effective treatment of the underlying OSA syndrome is administered  . "
[Show abstract][Hide abstract] 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.
59 habitually snoring children with various degrees of sleep-disordered breathing (age range, 4-16 years) 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 (1 min and 5 min) also were tested. Potential associations between evening-to-morning changes in EF and polysomnographic parameters were explored.
Evening-to-morning changes in children with OSA displayed severity-dependent deterioration of EF, and occlusions lasting 1 or 5 min during the reactive hyperemia test yielded similar findings.
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 · 3.15 Impact Factor
"In a trial looking at MDA plasma levels in severe OSA patients before and after 10 months of therapy, MDA levels fell significantly (Hernandez et al., 2006). An alternative therapy for mild OSA is an oral mandibular advancement device that moves the lower jaw forward; this therapy has also been shown to reduce MDA levels (Itzhaki et al., 2007). Overall, it seems that OSA contributes to elevated lipid peroxidation in individuals with moderate-severe OSA. "
[Show abstract][Hide abstract] ABSTRACT: Obstructive sleep apnea is increasingly recognized as an important contributor to cognitive impairment, metabolic derangements, and cardiovascular disease and mortality. Identifying the mechanisms by which this prevalent disorder influences health outcomes is now of utmost importance. As the prevalence of this disorder steadily increases, therapies are needed to prevent or reverse sleep apnea morbidities now more than ever before. Oxidative stress is implicated in cardiovascular morbidities of sleep apnea. What role oxidative stress plays in neural injury and cognitive impairments has been difficult to understand without readily accessible tissue to biopsy in persons with and without sleep apnea. An improved understanding of the role oxidative stress plays in neural injury in sleep apnea may be developed by integrating information gained examining neural tissue in animal models of sleep apnea with key features of redox biochemistry and clinical sleep apnea studies where extra-neuronal oxidative stress characterizations have been performed. Collectively, this information sets the stage for developing and testing novel therapeutic approaches to treat and prevent, not only central nervous system injury and dysfunction in sleep apnea, but also the cardiovascular and potentially metabolic conditions associated with this prevalent, disabling disorder.
Frontiers in Neurology 12/2012; 3:179. DOI:10.3389/fneur.2012.00179
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