The Effect of Continuous Positive Airway Pressure Therapy on Arterial Stiffness and Endothelial Function in Obstructive Sleep Apnea: A Randomized Controlled Trial in Patients Without Cardiovascular Disease

Study Questions:

What is the effect of continuous positive airway pressure (CPAP) on arterial stiffness and endothelial function in subjects with obstructive sleep apnea (OSA) in the absence of cardiovascular disease (CVD) or diabetes mellitus (DM)?


Men and women were recruited from a single-center Sleep Clinic. Subjects were excluded for previous CPAP therapy, respiratory failure, medications affecting blood pressure (BP), sleepiness when driving, professional driving, and contraindication to magnetic resonance imaging. Detailed medical history and records were examined to exclude a history of CVD or hypertension. A fasting venous glucose sample was taken to exclude DM. Data were collected from March 2007 to August 2008. All patients underwent attended overnight inpatient polysomnography and had moderate to severe OSA, defined as apnea-hypopnea index (AHI) ≥15 events/hour. Subjects were randomized in double-blinded fashion, placebo-controlled, in a crossover trial to examine effects of CPAP therapy on arterial stiffness and endothelial function. Patients were randomly assigned to 12 weeks of CPAP or sham therapy, achieved by setting the CPAP flow to the lowest possible setting and adding a flow-restricting connector and extra holes to the circuit, allowing air to escape. Arterial stiffness was measured by calculating the augmentation index (Alx) from radial artery pressure waveforms. Carotid-femoral (aortic) pulse wave velocity (PWV) was measured using a micromanometer by sequential acquisition of carotid and femoral pressure waveforms gated to the R-wave of a simultaneously recorded electrocardiogram. Cardiovascular magnetic resonance was used to determine aortic distensibility (AoD).


During the study period, 1,698 patients were initiated on CPAP in this laboratory. Initially, 166 patients were suitable for inclusion, but 113 (68%) were excluded, most declining to enroll. Of the 53 undergoing baseline assessment, only 43 finished all vascular studies, including crossover randomization to 12 weeks of CPAP and sham treatment of OSA. Average age was 49 years and 28 (65%) were men with average body mass index of 30 kg/m2 (27.3-31.6). Subjects used CPAP on average for 3 hours/night and sham for 2 hours/night. CPAP therapy lowered systolic BP (SBP) (126 mm Hg [standard deviation (SD) 12] vs. 129 mm Hg [SD, 14]; p = 0.03), with a trend toward reduced AIx (15.5 [SD, 11.9] vs. 16.6 [SD, 11.7]%; p = 0.08), but did not modify endothelial function. When subjects with (n = 24) and without (n = 19) excessive daytime sleepiness were separately examined, no effect of CPAP therapy on vascular function was seen. CPAP therapy did not have any effect on AoD.


The authors concluded that CPAP therapy lowered SBP, with a trend toward a reduction in AIx after 12 weeks. However, CPAP therapy had no effect on PWV, AoD, or endothelial function in this group of subjects without CVD after 12 weeks.


Because this study excluded patients with known CVD and DM, this cohort contained subjects with a lower overall risk profile. Additionally, this group had a smaller amount of time with intermittent hypoxia during sleep. Both may contribute to lack of observed treatment effect. Although the use of CPAP was low, post-hoc analysis of a subgroup using CPAP >4 hours/night did not demonstrate any change in vascular function. Last, it could be argued that a longer follow-up is needed to measure improvement in vascular function. Further studies are needed in OSA patients with no evidence of CVD to determine OSA treatment effects on development of CVD.

Clinical Topics: Prevention, Hypertension, Sleep Apnea

Keywords: Follow-Up Studies, Polysomnography, Pulse Wave Analysis, Continuous Positive Airway Pressure, Respiratory Insufficiency, Blood Pressure, Electrocardiography, Hypertension, Diabetes Mellitus, Sleep Apnea, Obstructive, Vascular Stiffness

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