Sleep-disordered Breathing, Snoring
Conditions
Brief summary
Upper airway obstruction (UAO) is an unrecognized source of hemodynamic stress that may contribute to aortic adverse events in persons with Marfan Syndrome (MFS). UAO occurs during snoring and sleep apnea and is characterized by repetitive partial or complete obstruction of the upper airway during sleep. These obstructive breathing events lead to intermittent surges in blood pressure (BP) REF and large decreases in pleural pressure (Pes), thereby increasing the trans-mural aortic pressure (TMP) and imposing mechanical stress on the aorta during sleep. Although UAO is known to increase mechanical stress on the aorta, the magnitude of the increase is not known for persons with MFS. In this project, therefore, the investigators will also examine the changes in Pes and BP responses in periods of obstructed breathing and compare the diurnal markers or vascular stress between Baseline and CPAP studies in MFS persons.
Detailed description
Research Objective/Significance: Specific Aim 1a: To quantify the Pes and BP during periods with and without UAO during sleep in persons with MFS. Specific Aim 1b: To examine the effect of CPAP treatment of UAO on Pes and BP in MFS persons. Specific Aim 2: To examine the effect of CPAP treatment of UAO on daytime markers of hemodynamic stress (augmentation index, reactive hyperemia index) in MFS persons. Primary Outcomes: * Overnight measure of hemodynamic stress (blood pressure, pleural pressure swings) Secondary Outcomes: * Changes in diurnal markers of hemodynamic stress (augmentation index, reactive hyperemia index)
Interventions
DEVICECPAP
Continuous positive airway pressure (CPAP). Room air at pressures between 6-8 centimeters of water (cmH2O) delivered via heated humidified tubing and a nasal mask.
Sponsors
The Marfan Foundation
National Institutes of Health (NIH)
Johns Hopkins University
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Participants will be assigned to a Baseline polysomnography and CPAP polysomnography in a randomized fashion. Participants will then be switched to the second polysomnography within 14 days of the first. The baseline polysomnography represents the exposure to sleep disordered breathing and the CPAP polysomnography represents the relief of the exposure. Markers of hemodynamic stress will be assessed in the morning after both studies.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
People with Marfan syndrome. * Age ≥ 18yrs * Able and willing to provide informed consent * Willing to sleep connected to research apparatus
Exclusion criteria
* Unstable cardiovascular disease (CHF, myocardial infarction or revascularization procedures, and unstable arrhythmias) * Uncontrolled hypertension (BP \> 190/110) * Underlying obstructive or other intrinsic lung disease * Renal failure on dialysis * Cirrhosis * Pregnancy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pleural Pressure (Pes) | Overnight on both CPAP and No CPAP nights | Pleural pressure (Pes) in mmHg monitored using an esophageal catheter. |
| Mean Arterial Blood Pressure (MAP) | Overnight on both Baseline and CPAP studies | Continuous blood pressure monitored using a non-invasive finger cuff. Data captured in mmHg. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Augmentation Index (AI) | 15 minutes in the morning post Baseline and CPAP studies | The AI (measured as percentage of pulse pressure) was assessed in the morning after both Baseline and CPAP studies. It is a measure of arterial stiffness that represents the degree of and can range from -10% to +10% in healthy individuals, with values generally higher in females and increases with age. |
| Reactive Hyperemia Index (RHI) | 15 minutes | The RHI is a measure of endothelial function that was measured in the morning after both Baseline and CPAP studies. It is unitless and scored on a range of 1 to 3 in healthy individuals with lower values indicating poor endothelial function. |
Countries
United States
Participant flow
Recruitment details
193 persons with Marfan syndrome were screened. Persons were recruited from the Johns Hopkins Marfan Clinic and the external Marfan Community via the Marfan foundation. Inclusion was based on a clinical diagnosis of Marfan syndrome (Ghent Criteria) or genetic testing. Persons were excluded if they had any chronic lung disease, other sleep disorders aside from sleep apnea, were on blood thinners, or had uncontrolled blood pressure. Recruitment occurred between 09/2018 and 11/2019.
Participants by arm
| Arm | Count |
|---|---|
| All Participants All participants enrolled in this study. | 31 |
| Total | 31 |
Baseline characteristics
| Characteristic | All Participants | — |
|---|---|---|
| Age, Continuous | 37.5 years STANDARD_DEVIATION 15.9 | — |
| Race and Ethnicity Not Collected | — | — Participants |
| Region of Enrollment United States | 31 Participants | — |
| Sex: Female, Male Female | 17 Participants | — |
| Sex: Female, Male Male | 14 Participants | — |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 30 | 0 / 31 |
| other Total, other adverse events | 0 / 30 | 0 / 31 |
| serious Total, serious adverse events | 0 / 30 | 0 / 31 |
Outcome results
Primary
Mean Arterial Blood Pressure (MAP)
Continuous blood pressure monitored using a non-invasive finger cuff. Data captured in mmHg.
Time frame: Overnight on both Baseline and CPAP studies
Population: Participants with upper airway obstruction (apneas, hypopneas, and flow limitation) during the Baseline sleep study, who had pleural pressure and blood pressure data collected during both Baseline and CPAP sleep studies.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Baseline Sleep Study | Mean Arterial Blood Pressure (MAP) | 93.8 mmHg | Standard Deviation 14 |
| CPAP Sleep Study | Mean Arterial Blood Pressure (MAP) | 88.3 mmHg | Standard Deviation 12.4 |
Primary
Pleural Pressure (Pes)
Pleural pressure (Pes) in mmHg monitored using an esophageal catheter.
Time frame: Overnight on both CPAP and No CPAP nights
Population: Participants with upper airway obstruction (apneas, hypopneas, and flow limitation) during the Baseline sleep study, who had pleural pressure and blood pressure data collected during both Baseline and CPAP sleep studies.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Baseline Sleep Study | Pleural Pressure (Pes) | 9.3 mmHg | Standard Deviation 3.4 |
| CPAP Sleep Study | Pleural Pressure (Pes) | 4.4 mmHg | Standard Deviation 1.6 |
Secondary
Augmentation Index (AI)
The AI (measured as percentage of pulse pressure) was assessed in the morning after both Baseline and CPAP studies. It is a measure of arterial stiffness that represents the degree of and can range from -10% to +10% in healthy individuals, with values generally higher in females and increases with age.
Time frame: 15 minutes in the morning post Baseline and CPAP studies
Population: Participants with adequate sleep time (\>2hrs) on both Baseline and CPAP studies and AI measurements after both Baseline and CPAP studies.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Baseline Sleep Study | Augmentation Index (AI) | 11.0 percentage of pulse pressure | Standard Error 3.8 |
| CPAP Sleep Study | Augmentation Index (AI) | 2.4 percentage of pulse pressure | Standard Error 3.7 |
Secondary
Reactive Hyperemia Index (RHI)
The RHI is a measure of endothelial function that was measured in the morning after both Baseline and CPAP studies. It is unitless and scored on a range of 1 to 3 in healthy individuals with lower values indicating poor endothelial function.
Time frame: 15 minutes
Population: Participants with adequate sleep time (\>2hrs) on both Baseline and CPAP studies and morning RHI measurements after both Baseline and CPAP studies.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Baseline Sleep Study | Reactive Hyperemia Index (RHI) | 2.2 score on a scale | Standard Error 0.1 |
| CPAP Sleep Study | Reactive Hyperemia Index (RHI) | 2.2 score on a scale | Standard Error 0.2 |