Endothelial Dysfunction, Monocyte Activation, and Vasculopathy in Patients With Obstructive Sleep Apnea (OSA) and Effect of 6-month CPAP Treatment

National Taiwan University

Status

Unknown

Conditions

Inflammation

Endothelium

Sleep Apnea, Obstructive

Continuous Positive Airway Pressure

Vascular Function

Treatments

Device: Therapeutic CPAP

Device: Subtherapeutic CPAP

Study type

Interventional

Funder types

Other

Identifiers

NCT01312168

201012085RB

Details and patient eligibility

About

This purpose of this study is to

Determine the change in endothelial dependent vascular reactivity and vascular properties
Determine the changes in monocytes activation
Determine the change in pro-inflammatory status
Investigate the effect of six-month CPAP therapy on the above changes in patients with OSA

Full description

Obstructive sleep apnea (OSA), characterized with chronic intermittent hypoxia (CIH) and sleep fragmentation, is associated with three-fold higher risk of cardiovascular events. CIH could promote production of ROS which induced the adhesion of circulating monocytes, endothelium injury, and production of pro-inflammatory mediators and adhesion molecules and lead to formation of atherosclerotic plaque. Recent studies showed vascular endothelium function could be noninvasively assessed with Flow-mediated dilation (FMD) in brachial artery, whereas OSA patients have lower FMD compared to control subjects. However, the CPAP effects on vascular function have conflicting results. Conflicts usually involve the small sample size, lack of appropriate control, and inadequate control of confounding factors, like physical activity, and duration of CPAP treatment. Also, CPAP effect on other monocytes activation and inflammatory mediators are clear as well. Our previous studies showed 12-week CPAP treatment could not modify the levels of TNF-α and hsCRP. However, the 12-week treatment may be not long enough to draw the conclusions for benefit from long-term CPAP therapy. Therefore, we plan to conduct a cross-sectional followed by a double blind, randomized, placebo-control, parallel-group interventional study to prove our hypothesis that OSA can lead to endothelial dysfunction, monocytes activation, and pro-inflammatory state which leads to and vasculopathy and those changes can be reverted by CPAP.

Enrollment

150 estimated patients

Sex

Male

Ages

30 to 65 years old

Volunteers

Accepts Healthy Volunteers

Inclusion and exclusion criteria

OSA patients

Inclusion Criteria:

male patients aged 30 to 65 year who have daytime sleepiness (ESS>=10)
newly diagnosed OSA (AHI>30/hr) by overnight PSG but never been treated

Exclusion Criteria:

unwilling or unable to perform testing procedure
past or current smoking history
medical condition (including cardiovascular disease, chronic pulmonary disease, diabetes, endocrinologic disease, chronic renal failure, and psychiatric disease)
systemic inflammatory conditions (system lupus erythematosus, rheumatoid arthritis, sarcoidosis, Crohn's disease, and ulcerative colitis)
active neurologic event
active infection two weeks prior to screening
enrolled in other trials in the study period
other sleep disorders
sleepy driver
using maintenance medications

Control subjects

Inclusion Criteria:

Age-, sex-, body weight-, height-matched subjects with enrolled OSA patients
non-sleepy
no OSA confirmed by home sleep study (AHI<5/hr)

Exclusion Criteria:

unwilling or unable to perform testing procedure
past or current smoking history
medical condition (including cardiovascular disease, chronic pulmonary disease, diabetes, endocrinologic disease, chronic renal failure, and psychiatric disease)
systemic inflammatory conditions (system lupus erythematosus, rheumatoid arthritis, sarcoidosis, Crohn's disease, and ulcerative colitis)
active neurologic event
active infection two weeks prior to screening
enrolled in other trials in the study period
other sleep disorders
using maintenance medications