Contribution of male sex, age, and obesity to mechanical instability of the upper airway during sleep

Abstract

Male sex, obesity, and age are risk factors for obstructive sleep apnea, although the mechanisms by which these factors increase sleep apnea susceptibility are not entirely understood. This study examined the interrelationships between sleep apnea risk factors, upper airway mechanics, and sleep apnea susceptibility. In 164 (86 men, 78 women) participants with and without sleep apnea, upper airway pressure-flow relationships were characterized to determine their mechanical properties [pharyngeal critical pressure under hypotonic conditions (passive Pcrit)] during non-rapid eye movement sleep. In multiple linear regression analyses, the effects of body mass index and age on passive Pcrit were determined in each sex. A subset of men and women matched by body mass index, age, and disease severity was used to determine the sex effect on passive Pcrit. The passive Pcrit was 1.9 cmH(2)O [95% confidence interval (CI): 0.1-3.6 cmH(2)O] lower in women than men after matching for body mass index, age, and disease severity. The relationship between passive Pcrit and sleep apnea status and severity was examined. Sleep apnea was largely absent in those individuals with a passive Pcrit less than -5 cmH(2)O and increased markedly in severity when passive Pcrit rose above -5 cmH(2)O. Passive Pcrit had a predictive power of 0.73 (95% CI: 0.65-0.82) in predicting sleep apnea status. Upper airway mechanics are differentially controlled by sex, obesity, and age, and partly mediate the relationship between these sleep apnea risk factors and obstructive sleep apnea.

Fig. 1

Women have decreased pharyngeal critical pressure under hypotonic conditions (passive Pcrit) compared with men. A ∼2.0-cmH₂O increase in passive Pcrit was observed in men compared with women (P < 0.02) in the entire group (left) and the male and female subgroups matched for respiratory disturbance index (RDI) and body mass index (BMI) (right). Values were adjusted for age and BMI. Line = median; box = 25th-50th percentiles; whiskers and cap = 95th percentile. Additional data points are represented that were outside the 5th and 95th percentiles. Bars = frequency histogram; dotted line = normal distribution plot; *P < 0.05.

Fig. 2

Passive Pcrit vs. BMI in men and women. In men and women, there was a significant correlation between the passive Pcrit and BMI (adjusted for age) for the entire sample of men and women. The magnitude of the change in Pcrit (solid lines) was 1.67 cmH₂O per 10 kg/m² change in BMI [95% confidence interval (CI): 1.20-2.15 cmH₂O per 10 kg/m²] in men (right) vs. 0.95 cmH₂O per 10 kg/m² change in BMI (95% CI: 0.32-1.57 cmH₂O per 10 kg/m²) in women (left). Note that the distribution of the subjects in the subset matched for RDI and BMI (closed symbols) did not differ from the distribution in the entire subject groups (open and closed symbols) for both men and women. Dashed lines represent 95% CIs.

Fig. 3

Passive Pcrit vs. age relationship in men and women. In the entire group, there was a significant correlation (solid line) between passive Pcrit and age (adjusted for BMI) in women, but not men (no line drawn). Note that the distribution of the subjects in the subset matched for RDI and BMI (closed symbols) did not differ from the distribution in the entire subject groups (open and closed symbols) for both men and women. Dashed lines represent 95% CIs.

Fig. 4

Passive Pcrit vs. RDI in all subjects. Sleep apnea prevalence (RDI > 10 events/h; see horizontal dashed line) and severity in non-rapid eye movement (NREM; left), rapid eye movement (REM; middle), and total sleep (right) increased with elevations in passive Pcrit. The presence of sleep apnea and sleep apnea severity increased markedly as passive Pcrit increased above -5 cmH₂O (see vertical dashed line), although there was substantial variability (○, women; ■, men).