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

University Of Washington, Seattle WA

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Abstract

Project Summary Individuals with Down syndrome (DS) (I-DS) are at a heightened risk of obstructive sleep apnea (OSA). Despite the well-established association of OSA with cardiovascular (CV) risks in the general population, whether such an association exists in I-DS is unknown. Despite the high rates of risk factors such as OSA and obesity, there is a suggestion of a lower risk of hypertension and atherosclerotic CV disease (CVD) in I-DS. In this regard, whether increased CV risks are present in I-DS with a high burden of OSA is uncertain. Clarifying the CV impact of OSA may unveil one mechanism by which I-DS are protected from these CV conditions. To address this, we propose a time-sensitive and cost-efficient supplementary study to the NHLBI- sponsored “Sleep Apnea-Specific Nocturnal BP Surge to Determine CV Risks and Therapeutic Benefits in Patients with OSA study R01HL158765” (SASBP study, Project period: 2021-2026). The scope of this project is within the scope of the parent study, which aims to identify blood pressure and other physiological responses to OSA as a way to explain the mediating mechanism of OSA and subclinical CV disease. This study would allow us to assemble a cohort of I-DS across the lifespan to perform deep phenotyping and study co-existing conditions (INvestigation of Co-occurring conditions across the Lifespan to Understand Down syndromE [INCLUDE] component 2) and to conduct clinical trials research inclusive of I-DS (INCLUDE component 3). We will recruit I-DS and control groups with OSA to achieve the following Aims. Aim 1 is to test the hypothesis that immediate CV consequences of OSA events are attenuated in I-DS compared to those without DS. We will compare immediate CV consequences (changes in heart rate and estimated blood pressure) with those of age-, sex-, BMI- and OSA severity- matched (n=15 each group). We will also compare the severity of OSA-related hypoxemia (hypoxic burden) and arousal tendency. Aim 2 is to test the hypothesis that in the presence of OSA, markers of subclinical CV disease are attenuated in I-DS than those without DS. We will compare daytime and nocturnal BP, arterial stiffness, and global longitudinal strain by echocardiography between the two groups. We will also examine the association between the degree of immediate CV consequences and the subclinical CV disease. This represents an inclusive mechanistic study focusing on I-DS with OSA, a major comorbid condition in this special population. The study's findings will facilitate risk stratification of I-DS with OSA and provide pivotal preliminary data to design future clinical trials to test the efficacy of OSA therapy in health outcomes of I-DS.