https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(05)71141-7.pdf

Long-term cardiovascular outcomes in men with obstructive sleep apnoea-hypopnoea with or without treatment with continuous positive airway pressure: an observational study

ContextSleep-disordered breathing (SDB) and sleep apnea have been linked to
hypertension in previous studies, but most of these studies used surrogate
information to define SDB (eg, snoring) and were based on small clinic populations,
or both.ObjectiveTo assess the association between SDB and hypertension in a large cohort
of middle-aged and older persons.Design and SettingCross-sectional analyses of participants in the Sleep Heart Health Study,
a community-based multicenter study conducted between November 1995 and January
1998.ParticipantsA total of 6132 subjects recruited from ongoing population-based studies
(aged ≥40 years; 52.8% female).Main Outcome MeasuresApnea-hypopnea index (AHI, the average number of apneas plus hypopneas
per hour of sleep, with apnea defined as a cessation of airflow and 
hypopnea defined as a ≥30% reduction in airflow
or thoracoabdominal excursion both of which are accompanied by a ≥4% drop in oxyhemoglobin
saturation), obtained by unattended home polysomnography. Other measures include
arousal index; percentage of sleep time below 90% oxygen saturation; history
of snoring; and presence of hypertension, defined as resting blood pressure
of at least 140/90 mm Hg or use of antihypertensive medication.ResultsMean systolic and diastolic blood pressure and prevalence of hypertension
increased significantly with increasing SDB measures, although some of this
association was explained by body mass index (BMI). After adjusting for demographics
and anthropometric variables (including BMI, neck circumference, and waist-to-hip
ratio), as well as for alcohol intake and smoking, the odds ratio for hypertension,
comparing the highest category of AHI (≥30 per hour) with the lowest category
(<1.5 per hour), was 1.37 (95% confidence interval [CI], 1.03-1.83; P for trend=.005). The corresponding estimate comparing
the highest and lowest categories of percentage of sleep time below 90% oxygen
saturation (≥12% vs <0.05%) was 1.46 (95% CI, 1.12-1.88; P for trend <.001). In stratified analyses, associations of hypertension
with either measure of SDB were seen in both sexes, older and younger ages,
all ethnic groups, and among normal-weight and overweight individuals. Weaker
and nonsignificant associations were observed for the arousal index or self-reported
history of habitual snoring.ConclusionOur findings from the largest cross-sectional study to date indicate
that SDB is associated with systemic hypertension in middle-aged and older
individuals of different sexes and ethnic backgrounds.

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Association of Sleep-Disordered Breathing, Sleep Apnea, and Hypertension in a Large Community-Based Study

background Previous studies have suggested that the obstructive sleep apnea syndrome may be an important risk factor for stroke. It has not been determined, however, whether the syndrome is independently related to the risk of stroke or death from any cause after adjustment for other risk factors, including hypertension. methods In this observational cohort study, consecutive patients underwent polysomnography, and subsequent events (strokes and deaths) were verified. The diagnosis of the obstructive sleep apnea syndrome was based on an apnea–hypopnea index of 5 or higher (five or more events per hour); patients with an apnea–hypopnea index of less than 5 served as the comparison group. Proportional-hazards analysis was used to determine the independent effect of the obstructive sleep apnea syndrome on the composite outcome of stroke or death from any cause. results Among 1022 enrolled patients, 697 (68 percent) had the obstructive sleep apnea syndrome. At baseline, the mean apnea–hypopnea index in the patients with the syndrome was 35, as compared with a mean apnea–hypopnea index of 2 in the comparison group. In an unadjusted analysis, the obstructive sleep apnea syndrome was associated with stroke or death from any cause (hazard ratio, 2.24; 95 percent confidence interval, 1.30 to 3.86; P=0.004). After adjustment for age, sex, race, smoking status, alcohol-consumption status, body-mass index, and the presence or absence of diabetes mellitus, hyperlipidemia, atrial fibrillation, and hypertension, the obstructive sleep apnea syndrome retained a statistically significant association with stroke or death (hazard ratio, 1.97; 95 percent confidence interval, 1.12 to 3.48; P=0.01). In a trend analysis, increased severity of sleep apnea at baseline was associated with an increased risk of the development of the composite end point (P=0.005). conclusions The obstructive sleep apnea syndrome significantly increases the risk of stroke or death from any cause, and the increase is independent of other risk factors, including hypertension.

https://www.nejm.org/doi/pdf/10.1056/NEJMoa043104

Obstructive sleep apnea as a risk factor for stroke and death.

The prevalence and related clinical features of obstructive sleep apnea-hypopnea (OSAH) in the general population were estimated in a two-phase cross-sectional study. The first phase, completed by 2,148 subjects (76.9%), included a home survey, blood pressure, and a portable respiratory recording, whereas in the second, subjects with suspected OSAH (n = 442) and a subgroup of those with normal results (n = 305) were invited to undergo polysomnography (555 accepted). Habitual snoring was found in 35% of the population and breathing pauses in 6%. Both features occurred more frequently in men, showed a trend to increase with age, and were significantly associated with OSAH. Daytime hypersomnolence occurred in 18% of the subjects and was not associated with OSAH. An apnea-hypopnea index (AHI) > or = 10 was found in 19% of men and 15% of women. The prevalence of OSAH (AHI > or = 5) increased with age in both sexes, with an odds ratio (OR) of 2.2 for each 10-yr increase. AHI was associated with hypertension after adjusting for age, sex, body mass index, neck circumference, alcohol use, and smoking habit. This study adds evidence for a link between OSAH and hypertension.

https://www.atsjournals.org/doi/pdf/10.1164/ajrccm.163.3.2005065

Obstructive sleep apnea-hypopnea and related clinical features in a population-based sample of subjects aged 30 to 70 yr.

Background: Sleep-disordered breathing is a common condition associated with adverse health outcomes including hypertension and cardiovascular disease. The overall objective of this study was to determine whether sleep-disordered breathing and its sequelae of intermittent hypoxemia and recurrent arousals are associated with mortality in a community sample of adults aged 40 years or older. Methods and Findings: We prospectively examined whether sleep-disordered breathing was associated with an increased risk of death from any cause in 6,441 men and women participating in the Sleep Heart Health Study. Sleep-disordered breathing was assessed with the apnea–hypopnea index (AHI) based on an in-home polysomnogram. Survival analysis and proportional hazards regression models were used to calculate hazard ratios for mortality after adjusting for age, sex, race, smoking status, body mass index, and prevalent medical conditions. The average follow-up period for the cohort was 8.2 y during which 1,047 participants (587 men and 460 women) died. Compared to those without sleep-disordered breathing (AHI: ,5 events/h), the fully adjusted hazard ratios for all-cause mortality in those with mild (AHI: 5.0–14.9 events/h), moderate (AHI: 15.0–29.9 events/h), and severe (AHI: $30.0 events/h) sleep-disordered breathing were 0.93 (95% CI: 0.80– 1.08), 1.17 (95% CI: 0.97–1.42), and 1.46 (95% CI: 1.14–1.86), respectively. Stratified analyses by sex and age showed that the increased risk of death associated with severe sleep-disordered breathing was statistically significant in men aged 40–70 y (hazard ratio: 2.09; 95% CI: 1.31–3.33). Measures of sleep-related intermittent hypoxemia, but not sleep fragmentation, were independently associated with all-cause mortality. Coronary artery disease–related mortality associated with sleepdisordered breathing showed a pattern of association similar to all-cause mortality. Conclusions: Sleep-disordered breathing is associated with all-cause mortality and specifically that due to coronary artery disease, particularly in men aged 40–70 y with severe sleep-disordered breathing. Please see later in the article for the Editors’ Summary.

/pdf/sleep-disordered-breathing-and-mortality-a-prospective-54wjrk24f4.pdf

Sleep-disordered breathing and mortality: A prospective cohort study

During 1976-1988 we diagnosed sleep apnea syndrome (SAS) in 1,620 adult men and women monitored in the Technion sleep laboratories. Their age at the time of diagnosis ranged between 21 and 79 years. Fifty-seven patients (53 men and 4 women) had died by 1990, 53% due to respiratory-cardiovascular causes. The observed/expected (O/E) mortality rates, calculated for men only, revealed excess mortality of patients under 70 years old. Excess mortality was significant in the fourth and fifth decades (3.33, p < 0.002; 3.23, p < 0.0002, respectively). In patients older than 70 O/E was 0.33 (p < 0.0007). Hierarchical multivariate analysis with four fixed variables [age, body mass index (BMI), hypertension and apnea index] and four additional variables added manually one at a time (heart disease, lung disease, diabetes, apnea duration) was used to determine the predictors of death from all causes, cardiopulmonary causes and from myocardial infarction (MI). All four major variables were found to be significant predictors of mortality from all causes, in addition to lung disease and heart disease. Only age and BMI were significant predictors of cardiopulmonary deaths in addition to lung disease. Age, BMI and hypertension predicted MI deaths in addition to lung disease. These results were interpreted to suggest that SAS affects death indirectly, most probably by being a risk factor for hypertension.

Mortality in Sleep Apnea Patients: A Multivariate Analysis of Risk Factors

A Crossover Study Comparing the Efficacy of Continuous Positive Airway Pressure With Anterior Mandibular Positioning Devices on Patients With Obstructive Sleep Apnea

The relationship between the severity of sleep apnea syndrome and 24-h blood pressure values in patients with obstructive sleep apnea

Objective:
To assess the efficacy, the compliance, and the complications of the anterior mandibular positioning (AMP) device in obstructive sleep apnea syndrome (OSA) patients.

Material & Methods:
Polysomnographic sleep studies were performed on 38 patients before and two weeks (± 3 days) after continuous use of the AMP device. Twenty patients also underwent polysomnographic follow-up recordings after 1 year.

Results:
The mean apnea-hypopnea index (AHI) before treatment was 35.6 ± 17.7 and decreased significantly to 22.7 ± 15.8 after 2 weeks of treatment (p = 0.01). The mean AHI after 1 year of usage was 25.3 ± 12.9, differing significantly from the pretreatment AHI (p = 0.01). Seventy-one percent of patients used the device for 18.4 months (range 12–27). One-year clinical evaluation showed preserved dental status, preserved action of the masticatory muscles, and preserved function of the temporo-mandibular joint (TMJ). Eleven (29%) of the patients did not use the AMP device because of TMJ pain and/or unsatisfying results.

Conclusions:
The AMP device is well tolerated in 76% of patient. When tolerated, its compliance and efficiency are preserved across the year without long-term oral and jaw dysfunctions. Laryngoscope, 119:585–588, 200

Short and long-term usage of a dental device in sleep apnea syndrome.

The efficacy of the anterior mandibular positioning (AMP) device in obstructive sleep apnea syndrome was assessed. This device advances the mandible anteriorly by approximately 5-7 mm. 29 patients were examined and questioned about temporomandibular (TM) and facial pain before and after treatment with the device. Polysomnographic sleep studies were performed on all before, and 2 weeks after continuous use of the AMP device. 10 of the patients also underwent polysomnographic follow-up after 1 year. The mean apnea index (AI) before treatment was 40.1, which decreased to 24.3 (p < 0.0001) after 14.3 days of treatment with the AMP device. O2 saturation also increased, from 84.2% before, to 89.2% after treatment (p < 0.002). In 10 patients the mean AI after 1 year was 24.9, not different from that after only 2 weeks of treatment, but significantly different from their mean AI before treatment (39.8). Use of the AMP device did not change blood saturation levels; neither did it affect dental status, action of the masticatory muscles, nor did it cause TM joint dysfunction. 21 patients (72.4%) have now been fitted with an AMP device, and the mean follow-up is 13.4 months (range 2-22); 3 have been using the AMP only intermittently for TM joint pain or discomfort. We conclude that the AMP device helps the majority of patients and is an alternative, nonsurgical method for treating obstructive sleep apnea syndrome.

Naama Yoffe

Papers

Mortality in Sleep Apnea Patients: A Multivariate Analysis of Risk Factors

A Crossover Study Comparing the Efficacy of Continuous Positive Airway Pressure With Anterior Mandibular Positioning Devices on Patients With Obstructive Sleep Apnea

The relationship between the severity of sleep apnea syndrome and 24-h blood pressure values in patients with obstructive sleep apnea

Short and long-term usage of a dental device in sleep apnea syndrome.

Treatment of obstructive sleep apnea with anterior mandibular positioning device