Treatment of obstructive sleep apnea improves cardiometabolic function in young obese women with polycystic ovary syndrome

Abstract

Context: Women with polycystic ovary syndrome (PCOS) are insulin resistant and have a high risk of early-onset diabetes and cardiovascular disease. Obstructive sleep apnea (OSA) has adverse cardiometabolic consequences and is highly prevalent in women with PCOS. We sought to determine whether continuous positive airway pressure (CPAP) treatment of OSA has beneficial effects on cardiometabolic function in PCOS.

Methods: Laboratory polysomnography and cardiometabolic measurements including insulin sensitivity and secretion (iv glucose tolerance test); 24-h profiles of plasma catecholamines, cortisol, and leptin; and daytime profiles of blood pressure and cardiac autonomic activity (heart rate variability) were obtained at baseline and again after 8 wk of home CPAP treatment with daily usage monitoring.

Results: CPAP treatment modestly improved insulin sensitivity after controlling for body mass index (P = 0.013). The change in insulin sensitivity correlated positively with CPAP use (adjusted P = 0.027) and negatively with body mass index (adjusted P = 0.003). Daytime and nighttime norepinephrine levels were decreased after CPAP (P = 0.002), and the reductions were greater with increased CPAP use (P = 0.03). Epinephrine, cortisol, and leptin levels were not changed significantly. Daytime diastolic blood pressure decreased by an average of 2.3 mm Hg after CPAP (P = 0.035). Cardiac sympathovagal balance was 44% lower (P = 0.007) after CPAP, reflecting a shift toward lower sympathetic activity.

Conclusions: In young obese women with PCOS, successful treatment of OSA improves insulin sensitivity, decreases sympathetic output, and reduces diastolic blood pressure. The magnitude of these beneficial effects is modulated by the hours of CPAP use and the degree of obesity.

Trial registration: ClinicalTrials.gov NCT00696111.

Fig. 1.

A, Fitted regression values of the change in insulin sensitivity after CPAP as a function of BMI and hours of CPAP use. The dark line represents the line of fit, and dotted lines represent the 95% confidence bands. Improvement in insulin sensitivity after CPAP was greatest among women with a lower BMI (β-coefficient = −1.068; adjusted P = 0.003) and was greater with more hours of CPAP use (β-coefficient = 7.132; adjusted P = 0.027). B, Modeled change in insulin sensitivity expected after 4, 6, and 8 h of CPAP use per night in an overweight patient with a baseline BMI of 28 kg/m² and in an obese patient with a baseline BMI of 35 kg/m². Predicted improvement in insulin sensitivity after treatment of OSA is more pronounced with longer hours of CPAP use in a dose-dependent manner and is of lesser magnitude in patients with higher degrees of obesity.

Fig. 2.

Mean (± sem) 24-h profiles of norepinephrine (A), epinephrine (B), cortisol (C), and leptin (D) before and after 8 wk of CPAP treatment. Gray bars indicate identical carbohydrate-rich meals (served at 1400, 1900, and 0900 h.) Black bars indicate time in bed. Leptin profiles before and after CPAP are expressed as the percentage of mean 24-h values before CPAP in each individual.

Fig. 3.

A, Mean (± sem) daytime (from 1400–2100 and from 0900–1400) profiles of systolic and diastolic blood pressure before and after 8 wk of CPAP treatment. The profiles are illustrated as smoothed data using a three-point moving average (i.e. a window width of 1 h). Mean daytime diastolic blood pressure decreased on average by 2.3 mm Hg after CPAP, whereas there was no significant change in mean daytime systolic blood pressure. B, Mean (± sem) daytime profiles of cardiac autonomic activity derived from HRV analysis of ECG recordings that were obtained during the hour preceding each meal (dinner, breakfast, and lunch) and before bedtime (between 2130 and 2200 h) during the 24-h blood sampling period. HFn is the normalized spectral power in the HF (0.15–0.40 Hz; used as a marker of vagal activity), and LFn is the normalized spectral power in the LF (0.04–0.14 Hz; used as a marker of sympathetic activity). LF to HF ratio (LF/HF; a marker of cardiac sympathovagal balance) was 44% lower after CPAP treatment, reflecting a shift toward lower sympathetic and higher parasympathetic activity.