Cardiovascular Effects After CPAP Withdrawal for Obstructive Sleep Apnea

Study Overview
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Brief Summary
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Background: Patients with obstructive sleep apnea run an increased risk of cardiovascular disease including hypertension. Continuous positive airway pressure (CPAP) is the first line of treatment. However, many patients skip CPAP for some nights. Aims: The primary aim was to investigate the cardiovascular effects of short-term CPAP withdrawal for five nights because of obstructive sleep apnea. Design: Randomized, parallel controlled trial Inclusion criteria: 100 patients with successful CPAP treatment for moderate to severe obstructive sleep apnea. Exclusion criteria: Dementia, heart infarction within 3 months, apnea hypopnea index > 10 with CPAP treatment. Randomization: 50 patients are randomized to sleep 5 days without CPAP and 50 patients to continue with CPAP treatment during the trial. Primary outcomes: Arterial stiffness, 24-hour blood pressure. Secondary outcomes: Effects of gender on outcome. Effects on brain natriuretic peptide, apnea-hypopnea index, oxygen desaturation-index, urine-catecholamines, blood lipids, C-reactive protein, glucose metabolism (S-glc, HBA1c), insulin resistance, serum creatinine, hemoglobin, daytime sleepiness (ESS, KSS), lung function (FVC, FEV1), airway inflammation (exhaled NO) Procedures: Sleep apnea investigation while patients are treated with CPAP for one night. Urinary samplings during the same night. They are also investigated with 24 h blood pressure measurements. Blood samples are taking fasting in the morning followed by measuring the arterial stiffness (Vicorder, Skidmore Medical UK) including pulse wave analysis using sphygmomanometer (Omron Japan). The same investigations are done at follow-up 5 days later where half of the patients have continued using CPAP treatment and half of them has slept without CPAP.

Detailed Description
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Patients fulfilling inclusion criteria are invited to the trial after informed consent for baseline and follow-up investigations. Baseline investigations Day 1 Patients are given a questionnaire. They are given blood pressure monitoring, (ABPM Medical 90217 ambulatory blood pressure monitor, Spacelab) for 24 hours a starting at 8-9 AM. They are also given sleep apnea recorder (Embletta, X 10 system, Embla systems, ResMed) for ambulatory use during the following night, and a container for urinary sampling during the night (urine norepinephrine). Day 2 Fasting on arrival. Return of the 24-h blood pressure recorder, the sleep apnea recorder and the urine sampling container. Blood samples at 08.15 am after resting for 15 minutes. Arterial stiffness is measured using arterial pulse wave velocity, radial artery applanation tonometry and office blood pressure. After resting, the measurements starts at 8.30 AM in a room with a temperature of 24°C. Pulse wave velocity (Vicorder, Skidmore Medical, Bristol, UK) is measured in the supine position. The augmentation index is derived from pulse wave analysis obtained from radial artery applanation tonometry on the right arm (SphygmoCor, AtCor Medical, Sydney, Australia). Lung function and exhaled NO measurements, ECG. Breakfast at around 10.00 am. CPAP time counter check Patients are then randomized with a ration of 1:1 to continue with CPAP or not for the following 5 nights. Follow-up measurements Day 6 They are given blood pressure monitoring, (ABPM Medical 90217 ambulatory blood pressure monitor, Spacelab) for 24 hours a starting at 8-9 AM. They are also given sleep apnea recorder (Embletta, X 10 system, Embla systems, ResMed) for ambulatory use during the following night, and a container for urinary sampling during the night (urine norepinephrine). Day 7 Fasting on arrival. CPAP time counter check Return of the 24-h blood pressure recorder, the sleep apnea recorder and the urine sampling container. Blood samples at 08.15 am after resting for 15 minutes. Arterial stiffness is measured using arterial pulse wave velocity, radial artery applanation tonometry and office blood pressure. After resting, the measurements starts at 8.30 AM in a room with a temperature of 24°C. Pulse wave velocity (Vicorder, Skidmore Medical, Bristol, UK) is measured in the supine position. The augmentation index is derived from pulse wave analysis obtained from radial artery applanation tonometry on the right arm (SphygmoCor, AtCor Medical, Sydney, Australia). Lung function and exhaled NO measurements, ECG. Breakfast at around 10.00 am. Trials ends and patients are told to continue with CPAP as usual.

Official Title
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Arterial Stiffness and Blood Pressure Changes After Continuous Positive Airway Pressure (CPAP) Withdrawal for Obstructive Sleep Apnea

Conditions
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Obstructive Sleep Apnea, Cardiovascular Disease

Intervention / Treatment
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* Procedure: Withdrawal of continuous positive airway pressure treatment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 years or older, given the written consent to participate in the study, 2 months to 2 years of continuous positive airway pressure (CPAP) treatments with good compliance (mean CPAP use of >4 hours/night) during the last month before inclusion moderate sleep apnea with Apnea Hypopnea Index >15 before treatment Exclusion Criteria: Apnea hypopnea index > 10 with CPAP treatment, heart infarction within 3 months prior to study participation, severe dementia, determined by study personal having psychological or physical hinder to participate in the study

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: No device, n=50<br>Withdrawal of device, continuous positive airway pressure treatment during 5 nights | Procedure: Withdrawal of continuous positive airway pressure treatment<br>* Withdrawal of continuous positive airway pressure treatment<br>|
| No Intervention: Continue using device, continuous positive airway pressure treatment n=50<br>Control group, Continue with device, continuous positive airway pressure treatment | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Arterial stiffness. | Arterial stiffness measured with Vicorder and pulse wave analysis | 5 days | 
| Systolic and diastolic blood pressure | 24 hour blood pressure measurements | 5 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Gender differences | Effect of gender on outcomes | 5 days | 
| Effect on myocardial function | Brain natriuretic peptide | 5 days | 
| Impact on apnea hypopnea index | apnea-hypopnea index | 5 days | 
| Effect on oxygen saturation | Oxygen desaturation index | 5 days | 
| Effect on catecholamines | measurements of urinary catecholamines during one day | 5 days | 
| Effect on blood lipids in the form triglycerides | serum triglycerides | 5 days | 
| Effect on blood lipids in the form of cholesterol | serum cholesterol | 5 days | 
| Effect on systemic inflammation. | C reactive protein (CRP) | 5 days | 
| Effect on glucose metabolism in the form of fasting glucose | Serum glucose obtained fasting in the morning | 5 days | 
| Long-term effect on glucose metabolism | serum HbA1c | 5 days | 
| Glucose metabolism in the form om Insulin levels | fasting serum insulin obtained in the morning. | 5 days | 
| Effect on renal function | serum creatinine | 5 days | 
| Effect on hemoglobin | serum hemoglobin | 5 days | 
| Assessment of daytime sleepiness for a past period of time | Epworth sleepiness scale | 5 days | 
| Daytime sleepiness assessed at a certain time point | Karolinska sleepiness scale | 5 days | 
| Effect on lung volumes | Vital capacity | 5 days | 
| Effect on airway obstructions | Forced vital capacity in one second | 5 days | 
| Effect on airway inflammation | Exhaled nitric oxide test | 5 days |