Hemodynamics Response to Upper Airway Obstruction in Marfan Syndrome (MSB)

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.

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)

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.

Baseline sleep polysomnography will involve the collection of electroencephalogram, electromyogram, electrocardiogram, airflow, heart rate, blood pressure, and pleural pressure during sleep with no CPAP. Participants in this arm would switch to CPAP within one week of the study.

Participants will be treated with continuous positive airway pressure to relieve sleep-disordered breathing. Participants in this arm would switch to Baseline study within one week of the study.

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.

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.

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.

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