The Effects of 1-Year Treatment With a Herbst Mandibular Advancement Splint on Obstructive Sleep Apnea, Oxidative Stress, and Endothelial Function

doi:10.1378/chest.06-0965

Chest

Volume 131, Issue 3, March 2007, Pages 740-749

https://doi.org/10.1378/chest.06-0965 Get rights and content

Abstract

Background: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 marke

Methods: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/m²), 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.

Results: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.

Conclusions: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.

Section snippets

Subjects

Patients were screened into the study from a pool of patients in whom OSA had been diagnosed by polysomnography and who had declined the use of nCPAP for lack of adjustment (the main stated reasons for refusal were claustrophobia, inconvenience, cost, nasal discomfort, and unappealing nature). Other inclusion criteria were an AHI of ≥ 10 and complaints of subjective sleepiness, forward jaw protrusion ability of at least 7 mm, and healthy teeth without dentures or movement. Exclusion criteria

Results

Of the 19 patients initially enrolled in the study, 3 dropped out due to ineffective treatment (ie, unchanged SDB despite maximum allowable jaw protrusion), and 16 continued in the study for 3 months. Two patients stopped using the MAS at 3 months, and of the 14 who continued using it with good compliance based on the results of their questionnaires, 12 underwent full assessment at 1 year and 2 refused to be restudied.Table 1 presents the demographic, clinical, and biochemical data of the study

Discussion

This is the first study to provide data on the long-term effects of MAS therapy on OSA and cardiovascular risk factors. The two major findings of our study are as follows: (1) treatment with the MAS may improve OSA both objectively and subjectively in patients with moderate and even severe OSA, and the MAS can thus be an alternative treatment when other treatment fails; and (2) the improvement in OSA severity tended to correlate with the improvement in cardiovascular pathophysiologic factors

References (51)

N Peled et al.
Nocturnal ischemic events in patients with obstructive sleep apnea syndrome and ischemic heart disease: effects of continuous positive air pressure treatment
J Am Coll Cardiol
(1999)
H Kraiczi et al.
Impairment of vascular endothelial function and left ventricular filling: association with the severity of apnea-induced hypoxemia during sleep
Chest
(2001)
K Christou et al.
Antioxidant capacity in obstructive sleep apnea patients
Sleep Med
(2003)
M Yamauchi et al.
Oxidative stress in obstructive sleep apnea
Chest
(2005)
GE Carpagnano et al.
8-Isoprostane, a marker of oxidative stress, is increased in exhaled breath condensate of patients with obstructive sleep apnea after night and is reduced by continuous positive airway pressure therapy
Chest
(2003)
JC Pepperell et al.
Ambulatory blood pressure after therapeutic and subtherapeutic nasal continuous positive airway pressure for obstructive sleep apnea: a randomized parallel trial
Lancet
(2002)
JM Marin et al.
Long term cardiovascular outcomes in men with obstructive sleep apnea-hypopnea with or without treatment with continuous positive airway pressure: an observational study
Lancet
(2005)
HM Engleman et al.
Improving CPAP use by patients with the sleep apnea/hypopnea syndrome (SAHS)
Sleep Med Rev
(2003)
WJ Randerath et al.
An individually adjustable oral appliance vs continuous positive airway pressure in mild-to-moderate obstructive sleep apnea syndrome
Chest
(2002)
GT Clark et al.
A crossover study comparing the efficacy of continuous positive airway pressure with anterior mandibular positioning devices on patients with obstructive sleep apnea
Chest
(1996)

Cited by (125)

Cardiovascular complications of pediatric obstructive sleep apnea
2023, Snoring and Obstructive Sleep Apnea in Children
Pediatric obstructive sleep apnea (OSA) leads to several comorbidities related to short and potentially long-term complications. In this chapter, the impact of pediatric OSA on the cardiovascular system is reviewed. Perturbations related to OSA, including sleep fragmentation, gas exchange abnormalities involving intermittent hypoxia and hypercapnia, and intrathoracic pressure changes related to respiration against an occluded upper airway, are all thought to be responsible for promoting cardiovascular disease (CVD). A review of the evidence implicating pediatric OSA with CVD will be examined by first reviewing cardiovascular complications that are subclinical or not easily clinically detectable, which include aberrations in the autonomic nervous system, systemic inflammation that is atherogenic, and finally, endothelial dysfunction. Next, the evidence for clinically detectable complications, including systemic hypertension and cardiac ventricular remodeling, will be reviewed. The evidence linking CVD to pediatric OSA should infer that untreated pediatric OSA will have a lasting impact on long-term cardiovascular health.
Mandibular advancement splints for the treatment of obstructive sleep apnea
2023, Encyclopedia of Sleep and Circadian Rhythms: Volume 1-6, Second Edition
Obstructive sleep apnea (OSA) is a chronic condition which lends itself to a comprehensive chronic disease management model, rather than a device-focused approach, so as to achieve the best possible health outcomes. Oral appliances are the main alternative to continuous positive airway pressure (CPAP) for the treatment of OSA. There has been an expansion of the research evidence to support the use of oral appliances in clinical practice and the clinical use of oral appliances for the treatment of OSA has become a mainstream practice.
Cardiovascular effects of oral appliance therapy in obstructive sleep apnea: A systematic review and meta-analysis
2018, Sleep Medicine Reviews
Obstructive sleep apnea (OSA) is associated with increased cardiovascular morbidity and mortality. This study systematically reviews the effects of oral appliance therapy (OAT) on a broad spectrum of cardiovascular outcomes.
A literature search was performed up to December 31st 2016. Twenty-five relevant full-text articles were retrieved. Sixteen articles were considered methodologically sufficient, including 11 randomized controlled trials.
Pooled data of the RCTs showed significant reductions in daytime systolic and diastolic blood pressure compared to baseline, but no significant reductions in heart rate, except for daytime heart rate when compared to inactive/placebo OAT. OAT and continuous positive airway pressure (CPAP) were equally effective in reducing blood pressure. Studies assessing the effect of OAT on heart rate variability, circulating cardiovascular biomarkers, and endothelial function and arterial stiffness, generally involved small numbers of patients, and were heterogeneous and inconclusive. Studies assessing the effect of OAT on cardiac function showed no effects on echocardiographic outcomes. One observational study showed that OAT was as effective as CPAP in reducing cardiovascular death.
It could be speculated that OAT may lead to a reduction in long-term cardiovascular morbidity and mortality in OSA patients. However, further methodologically high quality, longitudinal studies are warranted to address this key question.
Which place of pharmacological approaches beyond continuous positive airway pressure to treat vascular disease related to obstructive sleep apnea?
2018, Pharmacology and Therapeutics
Obstructive sleep apnea (OSA) is characterized by recurrent episodes of partial or complete upper airway obstruction, occurring during sleep, leading to chronic intermittent hypoxia (IH), which harms the cardiovascular system. OSA is associated with both functional and structural vascular alterations that contribute to an increased prevalence of fatal and non-fatal cardiovascular events. OSA is a heterogeneous disease with respect to the severity of hypoxia, the presence of daytime symptoms, obesity, and cardiovascular comorbidities. Various clusters of OSA phenotypes have been described leading to more highly personalized treatment. The aim of this review is to describe the various therapeutic strategies including continuous positive airway pressure (CPAP), oral appliances, surgery, weight loss, and especially pharmacological interventions that have been evaluated to reduce vascular alterations in both OSA patients and preclinical animal models. Conventional therapies, predominantly CPAP, have a limited impact on vascular alterations in the presence of co-morbidities. A better knowledge of pharmacological therapies targeting IH-induced vascular alterations will facilitate the use of combined therapies and is crucial for designing clinical trials in well-defined OSA phenotypes.
Sleep Disorders and Endothelial Dysfunction
2018, Endothelium and Cardiovascular Diseases: Vascular Biology and Clinical Syndromes
Obstructive sleep apnea (OSA) and sleep deprivation (SD) are common disturbances associated with increased cardiovascular risk. Although the precise mechanisms by which each of this disorders predisposes to cardiovascular disease are not completely understood, consistent evidence suggest that the components of OSA, particularly intermittent hypoxia, increased sympathetic activity, oxidative stress, and inflammation, among others, contribute to disrupt endothelial integrity and hamper endothelial repair capacity. Specific OSA treatment with continuous positive airway pressure (CPAP) is able to improve endothelial function and restore endothelial repair capacity. SD is also associated with sympathetic hyperactivity and vascular inflammation and endothelial dysfunction. Whether reversion of SD with lifestyle changes and sleep hygiene can improve endothelial dysfunction is not well established. In this chapter, we discuss the current evidence of the potential impact of OSA and SD on endothelial function, providing mechanistic insights and perspectives in this important research area.
Comparison of titrable thermoplastic versus custom-made mandibular advancement device for the treatment of obstructive sleep apnoea
2017, Respiratory Medicine
The disadvantages of custom-made mandibular advancement devices (MAD) for obstructive sleep apnoea (OSA) therapy are the cost and delay required to manufacture the device. This study aimed to evaluate the efficacy of a titrable, thermoplastic MAD compared to a custom-made MAD for OSA therapy.
In this prospective nonrandomized study, 158 patients with OSA from two French sleep centers were treated for 6 months with a titrable thermoplastic MAD (n = 86) or a custom-made MAD (n = 72). The primary outcome was the change in sleep-disordered breathing (SDB) severity.
After adjustment for baseline values, age, body mass index and study site, no significant intergroup differences were observed between thermoplastic and custom-made MAD for the outcome of apnoea, hypopnoea and oxygen desaturation indices. No between treatment differences were observed for the outcome of subjective sleepiness, symptoms of snoring and fatigue, depressive symptoms, and quality of life. Thermoplastic MAD therapy was associated with higher side effects scores for tooth pain (p < 0.0001) and self-reported occlusal changes (p = 0.0069). Mean (SD) reported compliance was lower in the thermoplastic MAD group than in the custom-made MAD group (6.4 [0.2] vs 7.1 [0.1] h/night; p = 0.035).
This study demonstrates the efficacy of a titrable thermoplastic MAD in reducing SDB and related symptoms in patients with mild to severe OSA. Reported compliance at 6 months was high despite more dental discomfort than with custom-made MAD.

View all citing articles on Scopus

: Equipment for this study was provided free of charge by Itamar-Medical. Dr. Peretz Lavie is a consultant and a board member of Itamar-Medical and SLP, and a board member of Sleep Medicine Center, Israel and SleepHealthCenters. Dr. Pillar is a consultant to Itamar-Medical. Drs. Itzhaki, Dorchin, Clark, and Lena Lavie have reported to the ACCP that no significant conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

View full text

Chest

Original ResearchThe Effects of 1-Year Treatment With a Herbst Mandibular Advancement Splint on Obstructive Sleep Apnea, Oxidative Stress, and Endothelial Function

Abstract

Section snippets

Subjects

Results

Discussion

J Am Coll Cardiol

Chest

Sleep Med

Chest

Chest

Lancet

Lancet

Sleep Med Rev

Chest

Chest

Chest

Am Heart J

J Am Coll Cardiol

Methods Enzymol

J Lipid Res

Sleep Med Rev

Respir Med

Chest

Prospective study of the association between sleep disordered breathing and hypertension

N Engl J Med

Obstructive sleep apnea syndrome as a risk factor for hypertension: population study

BMJ

Increased incidence of cardiovascular disease in middle-aged men with obstructive sleep apnea: a 7-year follow-up

Am J Respir Crit Care Med

Association of sleep-disordered breathing, sleep apnea, and hypertension in a large community-based study: Sleep Heart Health Study

JAMA

Obstructive sleep apnea: implications for cardiac and vascular disease

JAMA

Impairment of endothelium dependent vasodilation of resistance vessels in patients with obstructive sleep apnea

Circulation

Impaired vasodilator responses in obstructive sleep apnea are improved with continuous positive airway pressure therapy

Am J Respir Crit Care Med

Original Research
The Effects of 1-Year Treatment With a Herbst Mandibular Advancement Splint on Obstructive Sleep Apnea, Oxidative Stress, and Endothelial Function