The effect of continuous positive airway pressure on blood pressure in patients with obstructive sleep apnea and uncontrolled hypertension - Study design and challenges during the COVID-19 pandemic

Fernanda C.S.G Cruz,Luciano F Drager,Daniel B.C Queiróz,Gabriela A Souza,Rodrigo P Pedrosa,Tarcya L.G Couto Patriota,Egidio L Dórea,Marcelo Luiz C Vieira,Camila G Righi,Denis Martinez,Geruza A Da Silva,Giovanio V Silva,Andrea Pio-Abreu,Paulo A Lotufo,Isabela M Benseãor,Luiz A Bortolotto,Flávio D Fuchs,Geraldo Lorenzi-Filho

doi:10.6061/clinics/2021/e2926

Abstract

OBJECTIVES:To describe the MORPHEOS (Morbidity in patients with uncontrolled HTN and OSA) trial, and describe the challenges imposed by the COVID-19 pandemic.METHODS:MORPHEOS is a multicenter (n=6) randomized controlled trial designed to evaluate the blood pressure (BP) lowering effects of treatment with continuous positive airway pressure (CPAP) or placebo (nasal strips) for 6 months in adult patients with uncontrolled hypertension (HTN) and moderate-to-severe obstructive sleep apnea (OSA). Patients using at least one antihypertensive medication were included. Uncontrolled HTN was confirmed by at least one abnormal parameter in the 24-hour ABPM and ≥80% medication adherence evaluated by pill counting after the run-in period. OSA was defined by an apnea-hypopnea index ≥15 events/hours. The co-primary endpoints are brachial BP (office and ambulatory BP monitoring, ABPM) and central BP. Secondary outcomes include hypertension-mediated organ damage (HMOD) to heart, aorta, eye, and kidney. We pre-specified several sub-studies from this investigation. Visits occur once a week in the first month and once a month thereafter. The programmed sample size was 176 patients but the pandemic prevented this final target. A post-hoc power analysis will be calculated from the final sample. ClinicalTrials.gov: NCT02270658.RESULTS:The first 100 patients are predominantly males (n=69), age: 52±10 years, body mass index: 32.7±3.9 kg/m2 with frequent co-morbidities.CONCLUSIONS:The MORPHEOS trial has a unique study design including a run-in period; pill counting, and detailed analysis of hypertension-mediated organ damage in patients with uncontrolled HTN that will allow clarification of the impact of OSA treatment with CPAP.

Highlights

Obstructive sleep apnea (OSA) is characterized by recurrent episodes of upper airway obstruction during sleep leading to acute primary responses that are potentially harmful to the cardiovascular system, including excessive negative intrathoracic pressure due to futile effort to breath, sleep fragmentation, and intermittent hypoxia (1)
A body of evidence shows that the primary effects elicited by OSA during sleep trigger a cascade of intermediate responses, such as increased sympathetic activity during sleep but throughout the 24-hr period, that contributes to high blood pressure (BP) (5)
Exclusion Criteria Age 465 years old Body Mass Index X40 kg/m2 Heart failure, previous acute myocardial infarction and previous stroke left ventricular ejection fraction (LVEF) o45% determined by echocardiography Moderate or severe valvar disease Systolic BP 4180 mmHg or diastolic BP 4110 mmHg Secondary causes of HTN other than OSA Chronic renal failure with serum creatinine X2 mg / dL Pregnancy Cocaine, alcohol, amphetamines, and other illicit drug users Sympathomimetics use, oral contraceptives, and nonsteroidal anti-inflammatory drugs

Summary

Introduction

Obstructive sleep apnea (OSA) is characterized by recurrent episodes of upper airway obstruction during sleep leading to acute primary responses that are potentially harmful to the cardiovascular system, including excessive negative intrathoracic pressure due to futile effort to breath, sleep fragmentation, and intermittent hypoxia (1). OSA can contribute to increase the risk of developing HTN (6), contribute to poor BP control, and to blood vessel and heart remodeling (7)

Objectives

Methods

Discussion

Conclusion