Reduction in sympathetic tone in patients with obstructive sleep apnoea: is fixed CPAP more effective than APAP? A randomised, parallel trial protocol

Erika Treptow, Jean Louis Pepin, Sebastien Bailly, Patrick Levy, Cecile Bosc, Marie Destors, Holger Woehrle, Renaud Tamisier, Erika Treptow, Jean Louis Pepin, Sebastien Bailly, Patrick Levy, Cecile Bosc, Marie Destors, Holger Woehrle, Renaud Tamisier

Abstract

Introduction: Obstructive sleep apnoea (OSA) is a prevalent disease associated with cardiovascular events. Hypertension is one of the major intermediary mechanisms leading to long-term cardiovascular adverse events. Intermittent hypoxia and hypercapnia associated with nocturnal respiratory events stimulate chemoreflexes, resulting in sympathetic overactivity and blood pressure (BP) elevation. Continuous positive airway pressure (CPAP) is the primary treatment for OSA and induces a small but significant reduction in BP. The use of auto-adjusting positive airway pressure (APAP) has increased in the last years and studies showed different ranges of BP reduction when comparing both modalities. However, the pathophysiological mechanisms implicated are not fully elucidated. Variations in pressure through the night inherent to APAP may induce persistent respiratory efforts and sleep fragmentation that might impair sympathovagal balance during sleep and result in smaller decreases in BP. Therefore, this double-blind randomised controlled trial aims to compare muscle sympathetic nerve activity (MSNA) assessed by microneurography (reference method for measuring sympathetic activity) after 1 month of APAP versus fixed CPAP in treatment-naive OSA patients. This present manuscript describes the design of our study, no results are presented herein. and is registered under the below reference number.

Methods and analysis: Adult subjects with newly diagnosed OSA (Apnoea-Hypopnoea Index >20/hour) will be randomised for treatment with APAP or fixed CPAP. Measurements of sympathetic activity by MSNA, heart rate variability and catecholamines will be obtained at baseline and after 30 days. The primary composite outcome will be the change in sympathetic tone measured by MSNA in bursts/min and bursts/100 heartbeats. Sample size calculation was performed with bilateral assumption. We will use the Student's t-test to compare changes in sympathetic tone between groups.

Ethics and dissemination: The protocol was approved by The French Regional Ethics Committee. The study started in March 2018 with primary completion expected to March 2019. Dissemination plans of the results include presentations at conferences and publication in peer-reviewed journals.

Trial registration number: NCT03428516; Pre-results.

Keywords: continuous positive airway pressure; hypertension; obstructive sleep apnea; sleep medicine; sympathetic activity.

Conflict of interest statement

Competing interests: RT reports travel grants from Agiradom (a Home Healthcare provider) and research grants from Resmed.

© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1
Figure 1
Settings, acquisition, recording and reporting of muscle sympathetic nerve activity (MSNA). Measurement of MSNA is obtained by placement of an uninsulated tungsten register electrode in the peroneal nerve in the popliteal fossae or close to the fibula head. The objective is to reach postganglionic efferent sympathetic neurons. Potential voltage signal is recorded between the nerve electrode and a reference electrode placed on the external side of the knee. The acquired electrical signal is then amplified, band-filtered (700–2000 Hz), rectified and integrated. Sympathetic bursts, which correspond to nerve firing, are detected and scored using an automatic software in order to minimise subjective interpretation of the signal. MSNA results may be expressed in number of bursts per min or per 100 heartbeats, burst/min and bursts/100 heartbeats, respectively, or using the sum of areas under the curve of all burst in arbitrary integration units per minute or per 100 heartbeats, AUI/min and AUI/100 heartbeats, respectively.
Figure 2
Figure 2
Study protocol. APAP, auto-adjusting positive airway pressure; CPAP, continuous positive airway pressure; HRV, heart rate variability; MSNA, muscle sympathetic nerve activity.

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