Adverse effects of obstructive sleep apnea: Interindividual differences in symptoms and biomarkers

Introduction: Obstructive sleep apnea (OSA) is a common sleep disorder that is characterised by frequent cessation of breathing during sleep and excessive daytime sleepiness. Epidemiological studies show that at least 2-4% of the general population suffers from OSA and that the prevalence is much higher in obese subjects. OSA patients usually snore loudly but also have other more variable symptoms such as nocturnal sweating. It is important to recognise better the clinical symptoms of OSA as such knowledge is e.g. informative for the need of a sleep study in undiagnosed OSA patients. OSA is a known risk factor for cardiovascular disease (CVD) but some patients appear to be protected against the adverse consequences of OSA. It is important to understand this inter-individual difference better, e.g. by measuring inflammatory biomarkers as indicators of increased CVD risk. This information can be used for the development of personalized treatment of OSA and better prevention of its comorbidities. Objectives: To assess whether frequent nocturnal sweating is a symptom of OSA. To assess the relationship of OSA severity with levels of inflammatory biomarkers interleukin-6 (IL-6), C-reactive protein (CRP) and leptin in blood, independent of obesity. To evaluate the role of interindividual differences in both nocturnal sweating and levels of inflammatory biomarkers in blood. Methods: The relationship between OSA and reported nocturnal sweating was assessed by comparing 822 untreated OSA subjects in the Icelandic Sleep Apnea Cohort to 703 subjects in a general population cohort. The ISAC cohort was re-assessed two years after starting positive airway pressure (PAP) treatment (n=741). The OSA patients underwent a sleep study assessing OSA severity by four different indices; the apnea-hypopnea index (AHI), the oxygen desaturation index (ODI), hypoxia time (minutes with oxygen saturation <90%) and the minimum oxygen saturation (minSaO2) during the night. Magnetic resonance imaging of abdominal visceral and subcutaneous fat volume was performed. Objective nocturnal sweating was assessed by the electrodermal activity (EDA) index during sleep in a subset of 15 otherwise healthy OSA males while untreated and after 3 months of PAP treatment. Measurement of serum IL-6, CRP and leptin levels was performed cross-sectionally for the first 454 untreated OSA subjects in the ISAC cohort. Results: Frequent nocturnal sweating (≥3x a week) was reported by 31.1% of the OSA cohort vs. only 11.1% of the general population cohort (p<0.0001). This difference remained significant after adjustment for demographic factors. Nocturnal sweating was related to younger age, presence of CVD and hypertension, daytime sleepiness, and difficulties initiating and maintaining sleep but no gender differences were found. The prevalence of frequent nocturnal sweating decreased to 11.5% with PAP treatment (p<0.003). Also, in the 15 OSA patients with objective measures of sweating, the mean (±standard deviation) EDA index during sleep decreased from 132 (±22) events/hr. in untreated patients to 79 (±18) events/hr. on PAP treatment (p=0.04). Untreated patients with high EDA indices also had high systolic blood pressure in the evening and morning (p<0.01). A decrease in EDA index with treatment correlated with a decrease in systolic and diastolic blood pressure (p<0.05). In untreated ISAC participants (n=454), oxygen desaturation severity indices were significantly correlated with higher levels of IL-6, CRP and leptin, but AHI was not. When stratified by BMI category (BMI