Sleep Apnea, Obstructive, Continuous Positive Airway Pressure, Endothelium, Inflammation, Vascular Function
Conditions
Keywords
Cardiovascular disease, Continuous positive airway pressure, Endothelium, Vascular function, Inflammation, Sleep Apnea, Obstructive
Brief summary
This purpose of this study is to 1. Determine the change in endothelial dependent vascular reactivity and vascular properties 2. Determine the changes in monocytes activation 3. Determine the change in pro-inflammatory status 4. Investigate the effect of six-month CPAP therapy on the above changes in patients with OSA
Detailed 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.
Interventions
DEVICETherapeutic CPAP
CPAP ventilator, optimal pressure decided by CPAP manual titration, daily use at sleep, six months
DEVICESubtherapeutic CPAP
Subtherapeutic CPAP ventilator, pressure \<3 cmH2O, daily use at sleep, six months
Sponsors
China Medical University, China
National Taiwan University Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
MALE
Age
30 Years to 65 Years
Healthy volunteers
Yes
Inclusion 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)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| vascular reactivity of brachial artery and pulse wave velocity | six months |
Secondary
| Measure | Time frame |
|---|---|
| percentage of adhesion molecule expression on monocytes | six months |
| levels of extra and intracellular cytokine | six months |
Countries
Taiwan
Outcome results
None listed