Cardiovascular Effects After CPAP Withdrawal for Obstructive Sleep Apnea

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

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.

Study Overview

• Status: Completed
• Conditions: Cardiovascular Disease; Obstructive Sleep Apnea
• Intervention / Treatment: Procedure: Withdrawal of continuous positive airway pressure treatment

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 100
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Sweden
  • Umeå, Sweden, 901 85
    • Dept of Respiratory Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Umeå University
• Investigators: Principal Investigator: Karl A Franklin, Prof, MD, Umea University; Study Director: Carin Sahlin, PhD, Umea University

Study record dates

Study Major Dates

• Study Start (Actual): December 18, 2014
• Primary Completion (Actual): August 31, 2016
• Study Completion (Actual): August 31, 2016

Study Registration Dates

• First Submitted: December 12, 2014
• First Submitted That Met QC Criteria: December 30, 2014
• First Posted (Estimate): December 31, 2014

Study Record Updates

• Last Update Posted (Actual): March 3, 2023
• Last Update Submitted That Met QC Criteria: February 28, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Respiratory Tract Diseases; Respiration Disorders; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Signs and Symptoms, Respiratory; Sleep Apnea Syndromes; Sleep Apnea, Obstructive; Cardiovascular Diseases; Apnea
• Other Study ID Numbers: Dnr: 2010-329-31M