Lack of Association of the APOE ε4 Allele with the Risk of Obstructive Sleep Apnea: Meta-Analysis and Meta-Regression

Study Objectives:

Reports on the association of polymorphisms in the gene encoding apolipoprotein E (APOE)—a vital macromolecule in cholesterol metabolism—with obstructive sleep apnea (OSA) have provided conflicting results. Our objective was to meta-analytically synthesize the existing evidence for the association of the APOE ε4 allele with the risk of OSA.

Design:

Random effects meta-analysis and meta-regression

Setting:

Genetic epidemiological studies reporting the association of APOE ε4 allele with OSA susceptibility.

Patients or Participants:

Synthesis of APOE ε4 allele data from 6,508 subjects including 1,901 cases of OSA and 4,607 controls.

Interventions:

None

Measurements and Results:

Eight studies were included in the random effects meta-analysis; the summary effect size measured as odds ratio (OR) for association of the APOE ε4 allele with the risk of OSA was found to be 1.13 (95% confidence interval 0.86–1.47). There was a statistically significant heterogeneity (I² = 72%, P = 0.001) across study results that was not explained by the mean age, proportion of males, or the proportion possessing the APOE ε4 allele or when grouped based on the geographic location of the study.

Conclusions:

The hypothesis that the APOE ε4 allele may be causally associated with OSA cannot be supported on the basis of published literature.

Citation:

Thakre TP; Mamtani MR; Kulkarni H. Lack of association of the APOE ε4 allele with the risk of obstructive sleep apnea: meta-analysis and meta-regression. SLEEP 2009;32(11):1507-1511.     

Obstructive Sleep Apnea in New Zealand Adults: Prevalence and Risk Factors Among Māori and Non-Māori

Study Objectives:

Examine the distribution of symptoms and risk factors, and estimate the prevalence of obstructive sleep apnea (OSA) among Māori and non-Māori New Zealanders.

Design:

Mail-out survey to a stratified random sample from the electoral roll of 10,000 people aged 30-59 y, and overnight MESAM IV monitoring during sleep of a similarly aged stratified random sample of 364 people from the Wellington electoral roll.

Setting:

Nationwide survey of OSA symptoms (71% response rate) and regional home-based measurement of respiratory disturbance index (RDI, 4% oxygen desaturations/h of sleep, plus bursts of snoring or ≥ 10/min increase in heart rate).

Participants:

Sample designs aimed for equal numbers of Māori and non-Māori participants, men and women, and participants in each decade of age.

Interventions:

N/A

Measurements and results:

Māori were more likely than non-Māori to report OSAS risk factors and symptoms. After controlling for sex and age, Māori were 4.3 times more likely to have RDI ≥ 15 (95% CI = 1.3–13.9). Ethnicity was not an independent risk factor after controlling for body mass index (BMI) and neck circumference. The prevalence of OSAS (RDI ≥ 5 and ESS > 10) was conservatively estimated to be 4.4% for Māori men, 4.1% for non-Māori men, 2.0% for Māori women, and 0.7% for non-Māori women.

Conclusions:

The national survey and the regional monitoring study indicate a higher prevalence of OSA among Māori and among men. The higher prevalence among Māori appears to be attributable to recognized risk factors, notably body habitus. In addition to increased prevention and treatment services, strategies are needed to reduce ethnic disparities in OSAS prevalence.

Citation:

Mihaere KM; Harris R; Gander PH; Reid PM; Purdie G; Robson B; Neill A. Obstructive sleep apnea in New Zealand adults: prevalence and risk factors among māori and non-māori. SLEEP 2009;32(7):949-956.     

Catathrenia: Parasomnia or Uncommon Feature of Sleep Disordered Breathing?

OBJECTIVE: We report a series of seven consecutive cases of catathrenia (sleep related groaning) that differ from limited previous reports in the literature with regard to sleep stage and response to treatment. BACKGROUND: Catathrenia was recently defined as a parasomnia in the International Classification of Sleep Disorders Diagnostic and Coding Manual (ICSD-2), but there is debate about its classification, and its response to CPAP is unknown. METHODS: We present 7 consecutive patients presenting with catathrenia over a 5-year period. They were all young women, ranging in age from 20 to 34 years with a body mass index (BMI) <25. They underwent standard clinical evaluation, questionnaires, physical exam, craniofacial evaluations, and nocturnal polysomnography. All seven were titrated on continuous passive airway pressure (CPAP) treatment for sleep disordered breathing then offered surgical treatment if unable to tolerate or adhere to CPAP recommendations. RESULTS: Groaning was present throughout all stages of sleep. The mean (SD) AHI and RDI were 3.2 (0.56) and 13.1 (2.4) respectively. CPAP resolved groaning in all cases. 5 patients (71%) elected subsequent surgical intervention. Three of the 4 that followed up after surgery required adjuvant oral appliance treatment, but all four ultimately had resolution of groaning. CONCLUSIONS: Catathrenia may have subtypes related to sleep stage specificity or presence of sleep disordered breathing. In our heterogeneous group of non-obese women with a normal AHI and elevated RDI, CPAP and select soft tissue surgeries of the upper airway (often augmented with an oral appliance) successfully treated nocturnal groaning.     

Determinants of laser-evoked EEG responses: pain perception or stimulus saliency?

Although laser-evoked electroencephalographic (EEG) responses are increasingly used to investigate nociceptive pathways, their functional significance remains unclear. The reproducible observation of a robust correlation between the intensity of pain perception and the magnitude of the laser-evoked N1, N2, and P2 responses has led some investigators to consider these responses a direct correlate of the neural activity responsible for pain intensity coding in the human cortex. Here, we provide compelling evidence to the contrary. By delivering trains of three identical laser pulses at four different energies, we explored the modulation exerted by the temporal expectancy of the stimulus on the relationship between intensity of pain perception and magnitude of the following laser-evoked brain responses: the phase-locked N1, N2, and P2 waves, and the non-phase-locked laser-induced synchronization (ERS) and desynchronization (ERD). We showed that increasing the temporal expectancy of the stimulus through stimulus repetition at a constant interstimulus interval 1) significantly reduces the magnitudes of the laser-evoked N1, N2, P2, and ERS; and 2) disrupts the relationship between the intensity of pain perception and the magnitude of these responses. Taken together, our results indicate that laser-evoked EEG responses are not determined by the perception of pain per se, but are mainly determined by the saliency of the eliciting nociceptive stimulus (i.e., its ability to capture attention). Therefore laser-evoked EEG responses represent an indirect readout of the function of the nociceptive system.     

Consequences of Comorbid Sleep Apnea in the Metabolic Syndrome—Implications for Cardiovascular Risk

Study Objectives:

Metabolic syndrome (MetSyn) increases overall cardiovascular risk. MetSyn is also strongly associated with obstructive sleep apnea (OSA), and these 2 conditions share similar comorbidities. Whether OSA increases cardiovascular risk in patients with the MetSyn has not been investigated. We examined how the presence of OSA in patients with MetSyn affected hemodynamic and autonomic variables associated with poor cardiovascular outcome.

Design:

Prospective clinical study.

Participants:

We studied 36 patients with MetSyn (ATP-III) divided into 2 groups matched for age and sex: (1) MetSyn+OSA (n = 18) and (2) MetSyn-OSA (n = 18).

Measurements:

OSA was defined by an apnea-hypopnea index (AHI) > 15 events/hour by polysomnography. We recorded muscle sympathetic nerve activity (MSNA - microneurography), heart rate (HR), and blood pressure (BP - Finapres). Baroreflex sensitivity (BRS) was analyzed by spontaneous BP and HR fluctuations.

Results:

MSNA (34 ± 2 vs 28 ± 1 bursts/min, P = 0.02) and mean BP (111 ± 3 vs. 99 ± 2 mm Hg, P = 0.003) were higher in patients with MetSyn+OSA versus patients with MetSyn-OSA. Patients with MetSyn+OSA had lower spontaneous BRS for increases (7.6 ± 0.6 vs 12.2 ± 1.2 msec/mm Hg, P = 0.003) and decreases (7.2 ± 0.6 vs 11.9 ± 1.6 msec/mm Hg, P = 0.01) in BP. MSNA was correlated with AHI (r = 0.48; P = 0.009) and minimum nocturnal oxygen saturation (r = −0.38, P = 0.04).

Conclusion:

Patients with MetSyn and comorbid OSA have higher BP, higher sympathetic drive, and diminished BRS, compared with patients with MetSyn without OSA. These adverse cardiovascular and autonomic consequences of OSA may be associated with poorer outcomes in these patients. Moreover, increased BP and sympathetic drive in patients with MetSyn+OSA may be linked, in part, to impairment of baroreflex gain.

Citation:

Trombetta IC; Somers VK; Maki-Nunes C; Drager LF; Toschi-Dias E; Alves MJNN; Fraga RF; Rondon MUPB; Bechara MG; Lorenzi-Filho G; Negrão CE. Consequences of comorbid sleep apnea in the metabolic syndrome—implications for cardiovascular risk. SLEEP 2010;33(9):1193-1199.     

Sleep onset rapid-eye-movement episodes in narcolepsy: REM sleep pressure or nonREM-REM sleep dysregulation?

SUMMARY  Thirty-two narcoleptic subjects with excessive daytime sleepiness and cataplexy were recorded for 33 continuous hours. The continuous polysomnographic recording (CPSG) was followed by a standard MSLT at 2-h intervals. There were 64 sleep onset REM episodes (SOREMs) vs 64 sleep onset nonREM episodes (SONREMs) during the CPSG, and 102 SOREMs vs 50 SONREMS during the MSLT. Both sleep onset types peaked at 13–15 h during the CPSG while sleep onsets were evenly distributed during the MSLT. In the latter procedure, the mean sleep latency was significantly shorter with SOREMs occurrence than with SONREMs occurrence. Two factors were extracted in each procedure by means of a Varimax Rotated Factor Analysis. During the CPSG, SOREMs were related to the preceding nocturnal sleep parameters in the first factor, and to the daytime total sleep time and the total number of sleep onsets in the second factor. During the MSLT, SOREMs were related only to the mean sleep latency and the total number of sleep onsets. It was concluded that the occurrence of SOREMs is primarily due to the residual somnolence in narcoleptic subjects. However, their occurrence during the MSLT is largely independent of the prior history of sleep and waking. Thus, we propose a nonREM-REM sleep dysregulation hypothesis to account for the appearance of SOREMs in narcolepsy.     

Respiratory Flow–Sound Relationship During Both Wakefulness and Sleep and Its Variation in Relation to Sleep Apnea

Tracheal respiratory sound analysis is a simple and non-invasive way to study the pathophysiology of the upper airway and has recently been used for acoustic estimation of respiratory flow and sleep apnea diagnosis. However in none of the previous studies was the respiratory flow–sound relationship studied in people with obstructive sleep apnea (OSA), nor during sleep. In this study, we recorded tracheal sound, respiratory flow, and head position from eight non-OSA and 10 OSA individuals during sleep and wakefulness. We compared the flow–sound relationship and variations in model parameters from wakefulness to sleep within and between the two groups. The results show that during both wakefulness and sleep, flow–sound relationship follows a power law but with different parameters. Furthermore, the variations in model parameters may be representative of the OSA pathology. The other objective of this study was to examine the accuracy of respiratory flow estimation algorithms during sleep: we investigated two approaches for calibrating the model parameters using the known data recorded during either wakefulness or sleep. The results show that the acoustical respiratory flow estimation parameters change from wakefulness to sleep. Therefore, if the model is calibrated using wakefulness data, although the estimated respiratory flow follows the relative variations of the real flow, the quantitative flow estimation error would be high during sleep. On the other hand, when the calibration parameters are extracted from tracheal sound and respiratory flow recordings during sleep, the respiratory flow estimation error is less than 10%.     

Sleep problems: predictor or outcome of media use among emerging adults at university?

The pervasiveness of media use in our society has raised concerns about its potential impact on important lifestyle behaviours, including sleep. Although a number of studies have modelled poor sleep as a negative outcome of media use, a critical assessment of the literature indicates two important gaps: (i) studies have almost exclusively relied on concurrent data, and thus have not been able to assess the direction of effects; and (ii) studies have largely been conducted with children and adolescents. The purpose of the present 3‐year longitudinal study, therefore, was to examine whether both sleep duration and sleep problems would be predictors or outcomes of two forms of media use (i.e. television and online social networking) among a sample of emerging adults. Participants were 942 (71.5% female) university students (M = 19.01 years, SD = 0.90) at Time 1. Survey measures, which were assessed for three consecutive years starting in the first year of university, included demographics, sleep duration, sleep problems, television and online social networking use. Results of a cross‐lagged model indicated that the association between sleep problems and media use was statistically significant: sleep problems predicted longer time spent watching television and on social networking websites, but not vice versa. Contrary to our hypotheses, sleep duration was not associated with media use. Our findings indicate no negative effects of media use on sleep among emerging adults, but instead suggest that emerging adults appear to seek out media as a means of coping with their sleep problems.     

Your Place or Mine? Does the Sleep Location Matter in Young Couples?

This study sought to characterize the impact of sleep location (own sleeping environment vs. partner’s sleeping environment), social setting (sleeping in pairs vs. sleeping alone), and sex on sleep. An experimental 2 x 2 (sleep location x social setting) within-subject design was employed with 15 young heterosexual couples. The results suggest that sleep location does not appear to have a strong and consistent effect on sleep quantity or quality. The social setting had a specific effect in heterosexual young men, who were found to sleep longer and rise later when cosleeping with their partner. In contrast, we did not find any significant effect of the social setting on sleep continuity parameters in women. In both sexes, sleep quality was perceived to be better when sleeping in pairs. However, there was a higher concordance of the partners’ body movements in cosleeping nights compared to the sleeping alone condition.     

Primary Lymphoma of Pituitary Gland: A Neoplasm of Acquired Malt?

A 66-yr-old man presented with presyncopal episodes, dizziness, anorexia, nausea, and weight loss and was noted to have low blood pressure with a postural drop and sparse eyebrows. Laboratory investigations revealed evidence of hypopituitarism. Magnetic resonance imaging (MRI) revealed a non-enhancing mass arising from the adenohypophysis. The neurohypophysis was displaced laterally but appeared otherwise normal. The lesion was thought to be a nonfunctioning pituitary adenoma and a trans-sphenoidal hypophysectomy was performed. Histologically, this lesion was a diffuse large B-cell lymphoma that had features of a high grade mucosa associated lymphoid tissue (MALT)-type lymphoma arising in association with low-grade B-cell lymphoma of MALT type. There was no clinical or radiological evidence of lymphoma in other sites and there was no evidence of an immunocompromised state. Only one previous case of primary malignant lymphoma of the pituitary has been reported and this patient presented with compression of the optic chiasm. We describe the clinical and pathological features of a patient who presented with hypopituitarism and was found to have a pituitary lymphoma. This is the first reported case of a pituitary lymphoma presenting with pituitary failure and the first case characterized by lymphocyte-marker studies that confirmed it to be a B-cell lymphoma.     

Is Transfer of Acquired Coordination of Head and Forepaw Movements Possible in Dogs?

Dogs were trained to tonic elevation of the forepaw and to use a lever to lift and maintain in position a food-containing cup during eating, this being accompanied by inclination of the head towards the feeder. In the conditions used here, the pretraining situation was that dogs would elevate the paw with an anticipatory upward movement of the lowered head; when the head tilted to the feeder, the paw flexed. The effect of special training, in which the initial coordination of the head and paw movements were remodeled, was that the animals maintained the paw elevated with the head in the lowered position. Dogs trained to perform the operant response with one paw did not transfer the acquired reaction when the working paw was changed. After the first training, the initial coordination was changed only between movements of the head and the working limb, but not between head movements and the non-trained paw. Remodeling of the initial movement coordination of the head with the second paw also occurred only as a result of the learning process.     

Determinants of social inequalities in child mortality in Mozambique: what do we know? What could be done?

Health inequalities are no longer an issue only for developed countries. In recent years there is agreement that all countries present health inequalities regardless of their level of wealth. In low-income countries and especially in sub-Saharan Africa where the majority of the poor people live as well as their children, research on child health inequalities is still scarce. This review of evidence suggests that if Mozambique is to achieve the millennium development goals (MDGs) by 2015 further research on important determinants of disparities in child mortality is urgently needed.