Heritability of performance deficit accumulation during acute sleep deprivation in twins.

STUDY OBJECTIVES: To determine if the large and highly reproducible interindividual differences in rates of performance deficit accumulation during sleep deprivation, as determined by the number of lapses on a sustained reaction time test, the Psychomotor Vigilance Task (PVT), arise from a heritable trait. DESIGN: Prospective, observational cohort study. SETTING: Academic medical center. PARTICIPANTS: There were 59 monozygotic (mean age 29.2 ± 6.8 [SD] yr; 15 male and 44 female pairs) and 41 dizygotic (mean age 26.6 ± 7.6 yr; 15 male and 26 female pairs) same-sex twin pairs with a normal polysomnogram. INTERVENTIONS: Thirty-eight hr of monitored, continuous sleep deprivation. MEASUREMENTS AND RESULTS: Patients performed the 10-min PVT every 2 hr during the sleep deprivation protocol. The primary outcome was change from baseline in square root transformed total lapses (response time ≥ 500 ms) per trial. Patient-specific linear rates of performance deficit accumulation were separated from circadian effects using multiple linear regression. Using the classic approach to assess heritability, the intraclass correlation coefficients for accumulating deficits resulted in a broad sense heritability (h(2)) estimate of 0.834. The mean within-pair and among-pair heritability estimates determined by analysis of variance-based methods was 0.715. When variance components of mixed-effect multilevel models were estimated by maximum likelihood estimation and used to determine the proportions of phenotypic variance explained by genetic and nongenetic factors, 51.1% (standard error = 8.4%, P < 0.0001) of twin variance was attributed to combined additive and dominance genetic effects. CONCLUSION: Genetic factors explain a large fraction of interindividual variance among rates of performance deficit accumulations on PVT during sleep deprivation.

Noninferiority of functional outcome in ambulatory management of obstructive sleep apnea.

RATIONALE: Home portable monitor testing is increasingly being used to diagnose patients with obstructive sleep apnea (OSA) and to initiate them on continuous positive airway pressure (CPAP) treatment. OBJECTIVES: To compare functional outcome and treatment adherence in patients who receive ambulatory versus in-laboratory testing for OSA. METHODS: Veterans with suspected OSA were randomized to either home testing or standard in-laboratory testing. Home testing consisted of a type 3 portable monitor recording followed by at least three nights using an automatically adjusting positive airway pressure apparatus. Participants diagnosed with OSA were treated with CPAP for 3 months. MEASUREMENTS AND MAIN RESULTS: We measured the change in Functional Outcomes of Sleep Questionnaire score, with an a priori noninferiority delta of -1, and the mean daily hours of objectively measured CPAP adherence, with an a priori noninferiority delta of -0.75 hour/day. Of the 296 subjects enrolled, 260 (88%) were diagnosed with OSA, and 213 (75%) were initiated on CPAP. Mean ± SD functional outcome score improved 1.74 ± 2.81 in the home group (P < 0.001) and 1.85 ± 2.46 in the in-laboratory group (P < 0.0001). The lower bound of the one-sided 95% noninferiority confidence interval was -0.54. Mean ± SD hours of daily CPAP adherence were 3.5 ± 2.5 hours/day in the home group and 2.9 ± 2.3 hours/day in the in-laboratory group (P = 0.08). The lower bound of the one-sided 95% noninferiority confidence interval was 0.03. CONCLUSIONS: Functional outcome and treatment adherence in patients evaluated according to a home testing algorithm is not clinically inferior to that in patients receiving standard in-laboratory polysomnography.

Family aggregation of upper airway soft tissue structures in normal subjects and patients with sleep apnea.

RATIONALE: Sleep apnea is believed to be a genetic disorder. Thus, we hypothesized that anatomic risk factors for sleep apnea would demonstrate family aggregation. OBJECTIVES: We used volumetric magnetic resonance imaging in a sib pair "quad" design to study the family aggregation of the size of upper airway soft tissue structures that are associated with increased risk for obstructive sleep apnea. METHODS: We examined 55 sleep apnea probands (apnea-hypopnea index [AHI]: 43.2 +/- 26.3 events/h), 55 proband siblings (AHI: 11.8 +/- 16.6 events/h), 55 control subjects (AHI: 2.1 +/- 1.7 events/h), and 55 control siblings (AHI: 4.2 +/- 4.0 events/h). The study design used exact matching on ethnicity and sex, frequency matching on age, and statistical control for visceral neck fat and craniofacial dimensions. MEASUREMENTS AND MAIN RESULTS: The data support our a priori hypothesis that the volume of the important upper airway soft tissue structures is heritable. The volume of the lateral pharyngeal walls (h(2) = 36.8%; p = 0.001), tongue (h(2) = 36.5%; p = 0.0001), and total soft tissue (h(2) = 37.5%; p = 0.0001) demonstrated significant levels of heritability after adjusting for sex, ethnicity, age, visceral neck fat, and craniofacial dimensions. In addition, our data indicate that heritability of the upper airway soft tissue structures is found in normal subjects and patients with apnea. Thus, it is not simply a consequence of the prevalence of apnea. CONCLUSIONS: This is the first time family aggregation of size of the upper airway soft tissue structures has been demonstrated.

Identification of upper airway anatomic risk factors for obstructive sleep apnea with volumetric magnetic resonance imaging.

We used sophisticated volumetric analysis techniques with magnetic resonance imaging in a case-control design to study the upper airway soft tissue structures in 48 control subjects (apnea-hypopnea index, 2.0 +/- 1.6 events/hour) and 48 patients with sleep apnea (apnea-hypopnea index, 43.8 +/- 25.4 events/hour). Our design used exact matching on sex and ethnicity, frequency matching on age, and statistical control for craniofacial size and visceral neck fat. The data support our a priori hypotheses that the volume of the soft tissue structures surrounding the upper airway is enlarged in patients with sleep apnea and that this enlargement is a significant risk factor for sleep apnea. After covariate adjustments the volume of the lateral pharyngeal walls (p < 0.0001), tongue (p < 0.0001), and total soft tissue (p < 0.0001) was significantly larger in subjects with sleep apnea than in normal subjects. These data also demonstrated, after covariate adjustments, significantly increased risk of sleep apnea the larger the volume of the tongue, lateral pharyngeal walls, and total soft tissue: (1) total lateral pharyngeal wall (odds ratio [OR], 6.01; 95% confidence interval [CI], 2.62-17.14); (2) total tongue (OR, 4.66; 95% CI, 2.31-10.95); and (3) total soft tissue (OR, 6.95; 95% CI, 3.08-19.11). In a multivariable logistic regression analysis the volume of the tongue and lateral walls was shown to independently increase the risk of sleep apnea.