Arterial Stiffness and Blood Pressure Changes After Continuous Positive Airway Pressure (CPAP) Withdrawal for Obstructive Sleep Apnea
Phase: NA
Conditions: Obstructive Sleep Apnea, Cardiovascular Disease
Sponsor: Umeå University

 
Study Protocol 
 
Cardiovascular effects after CPAP withdrawal for obstructive sleep 
apnea 
 
NCT number: 02329470 
 
Document date: October 2013  
 
 
 
 

Background 
Sleep apnea is common in the population and in a newly published population study 
of 400 women we found that 50% of them had sleep apnea and 20% had moderate 
and severe sleep apnea (1). More than 30,000 people in Sweden are being 
investigated per years for sleep apnea. The most common and effective treatment is 
CPAP (2-4). Many people use CPAP all and whole nights while others sometimes 
sleep without CPAP one or a few nights a week. However, it has not been studied 
whether it is dangerous to sleep without CPAP for a few nights. 
 
Blood pressure and heart rate rise due to a stress surge and oxygenation drops 
during an obstructive apnea. Patients with obstructive sleep apnea are at increased 
risk of cardiovascular disease such as hypertension, myocardial infarction, stroke 
and premature death (5-6). We have previously shown that nocturnal angina is 
triggered by obstructive sleep apnea (7). Systemic inflammation and impaired blood 
vessel function including endothelial function are also associated with obstructive 
sleep apnea (8). 
 
The arterial stiffness of the central arteries is mainly determined by the compliance of 
the aorta and increases with an impaired function of elastic fibers. Arterial stiffness 
increases with age, diabetes mellitus, inflammation, hypertension, obesity, smoking, 
cholesterol levels and atherosclerotic disease (9). Increased arterial stiffness is an 
independent risk factor for morbidity and death in cardiovascular disease (10). 
Arterial stiffness measurement is a validated and widespread method to assess 
endothelial function. 
 
Many patients sometimes sleep without their CPAP. It is important from a clinical 
point of view to know if the cardiovascular system is affected by CPAP withdrawal for 
some nights.  
 
Aims 
The primary aim was to investigate the cardiovascular effects of short-term CPAP 
withdrawal for five nights in women and men with obstructive sleep apnea. 
 
Design 
Randomized, parallel controlled trial 
 
Inclusion Criteria 
Men and women aged 18 years old with moderate to severe obstructive sleep apnea 
and successful CPAP treatment for 2 months to 2 years with good compliance (mean 
CPAP use of >4 hours/night) during the last month before inclusion. Signed written 
consent to participate in the study. 
 
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 
 
 

Randomization 
50 patients are randomized to sleep 5 days without CPAP and 50 patients to 
continue with CPAP treatment during the trial. Randomization is done by a person 
outside the study. 
 
Primary outcomes 
Arterial stiffness measured with pulse wave velocity, and 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), serum-insulin, 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. 
 
Power calculation 
It was estimated that 90 patients, 45 in each group, would be needed to detect a 
mean (SD) blood pressure difference of 3 (5) mm Hg with a power of 80% and a 
significance level of 5%. It was estimated that 34 patients, 17 in each group, would 
be needed to detect a mean (SD) difference of 1 (1) m/s in pulse wave velocity with a 
power of 80% and a significance level of 5%. 
 
Procedures 
100 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 investigation equipment (Embletta, X 10 system, Embla systems, ResMed) for 
ambulatory use during the following night, and a container for urinary sampling during 
the night for measurements of urine norepinephrine. 
 
Day 2 Fasting on arrival. Return of the 24-h blood pressure recording, the sleep 
apnea recording 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 start 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 
recording, the sleep apnea recording 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. 
The trials ends and patients are told to continue with CPAP as usual. 
 
Significance 
Previous studies report that CPAP treatment has a beneficial effect on arterial 
stiffness. It is unknown whether it is dangerous to sleep without CPAP for a few days, 
which many patients with obstructive sleep apnea sometimes do. We will investigate 
whether it is hazardous for patients to be without CPAP for a few days by examining 
arterial stiffness and 24-hour blood pressure after 5 nights without CPAP in a 
randomized controlled trial. 
 
Ethical considerations 
Blood tests on the patients and this can cause some discomfort, but all blood 
sampling is done by experienced staff. Measuring arterial stiffness does not cause 
any discomfort. 
 
Sex perspective 
Both men and women of different ages are included in the study. We aim analyze 
women and men in separate. 
 
References 
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occurrence in women. Eur Respir J. Online aug 2012. Published ahead of 
print 2012. 

 
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