R01HL158765

Sleep Apnea-Specific Nocturnal Blood Pressure Surge to Determine Cardiovascular Risks and Therapeutic Benefits in Patients with Obstructive Sleep Apnea - Abstract

Obstructive Sleep Apnea (OSA) is a common sleep disorder associated with an increased risk of cardiovascular (CV) disease. However, it remains uncertain whether treatment of OSA improves CV outcomes given the lack of evidence from recent clinical trials.

We hypothesize that characterizing repetitive nighttime blood pressure (BP) surges following sleep apnea events improves risk stratification in OSA and helps identify those who benefit most from therapy.

OSA is a major risk factor for nocturnal hypertension, a well-established prognostic marker for adverse CV outcomes, including mortality. Therefore, it is plausible that nocturnal hypertension acts as a mediator between OSA and CV morbidity and mortality.

However, continuous BP is not currently quantified in clinical sleep studies for OSA evaluation, while the conventional ambulatory BP monitoring device that intermittently measures BP is unable to capture BP surges associated with sleep apnea events.

To capture sleep apnea-specific episodic BP increase, we will use a recently validated finger-cuff-based beat-to-beat BP device to monitor nocturnal BP during polysomnography (PSG).

In this time-sensitive ancillary study, we propose to examine the extent to which sleep apnea-specific BP increase is associated with an increased risk for CV outcomes (Aim 1, cross-sectional study); and whether individuals with higher sleep apnea-specific BP surges respond more favorably to continuous positive airway pressure (CPAP) therapy in terms of reduction in CV risks (Aim 2, prospective study).

In addition, we will examine the race-specific differences between white and African American in the degree of sleep apnea-specific BP increase and whether the associations examined in Aims 1 and 2 are modified by race (Aim 3).

To achieve these aims, we will leverage the infrastructure and resources of the ongoing NHLBI sponsored parent study at the Brigham and Women's Hospital (N~160) in which novel PSG-derived physiological metrics are being investigated to evaluate their utilities for predicting CV responses to 12-week CPAP therapy in people with OSA.

We will add continuous beat-to-beat BP monitoring to PSG recording performed at the baseline study of the parent study. The primary CV outcome will be left ventricular strain by speckle tracking echocardiography, which is a sensitive marker for subclinical mechanical left ventricular dysfunction.

Secondary CV outcomes will include other conventional echocardiographic measures of structural and functional remodeling, electrocardiographic marker of left atrial electrical remodeling, and arterial stiffness by pulse wave velocity.

We will also recruit additional African Americans to have sufficient statistical power in Aim 3.

The major innovation of this proposal is the incorporation of the continuously measured nocturnal BP and other PSG-derived physiological measurements into the clinical decision making.

Our study design allows for race-specific investigation with the goal of better understanding the mechanisms linking OSA to the existing CV health disparity in African Americans.

University Of Washington

THE NATIONAL CENTER ON SLEEP DISORDERS RESEARCH (NCSDR) SUPPORTS RESEARCH AND RESEARCH TRAINING RELATED TO SLEEP DISORDERED BREATHING, AND THE FUNDAMENTAL FUNCTIONS OF SLEEP AND CIRCADIAN RHYTHMS. THE CENTER ALSO STEWARDS SEVERAL FORUMS THAT FACILITATE THE COORDINATION OF SLEEP RESEARCH ACROSS NIH, OTHER FEDERAL AGENCIES AND OUTSIDE ORGANIZATIONS, INCLUDING THE SLEEP DISORDERS RESEARCH ADVISORY BOARD AND AN NIH-WIDE SLEEP RESEARCH COORDINATING COMMITTEE. THE CENTER ALSO PARTICIPATES IN THE TRANSLATION OF NEW SLEEP RESEARCH FINDINGS FOR DISSEMINATION TO HEALTH CARE PROFESSIONALS AND THE PUBLIC. SMALL BUSINESS INNOVATION RESEARCH (SBIR) PROGRAM: TO STIMULATE TECHNOLOGICAL INNOVATION, USE SMALL BUSINESS TO MEET FEDERAL RESEARCH AND DEVELOPMENT NEEDS, FOSTER AND ENCOURAGE PARTICIPATION IN INNOVATION AND ENTREPRENEURSHIP BY SOCIALLY AND ECONOMICALLY DISADVANTAGED PERSONS, AND INCREASE PRIVATE-SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT FUNDING. SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAM: TO STIMULATE TECHNOLOGICAL INNOVATION, FOSTER TECHNOLOGY TRANSFER THROUGH COOPERATIVE R&D BETWEEN SMALL BUSINESSES AND RESEARCH INSTITUTIONS, AND INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL R&D.

93.310 - Trans-NIH Research Support

National Heart Lung and Blood Institute (NHLBI) [HHS - NIH]

National Institute of Allergy and Infectious Diseases (NIAID) [HHS - NIH]

Seattle, Washington 981951016 United States

Single Zip Code

Administrative Supplements to Existing NIH Grants and Cooperative Agreements (Parent Admin Supp Clinical Trial Optional) (PA-20-272)

Amendment Since initial award the total obligations have increased 496% from $584,161 to $3,481,554.