Decrease Obstructive Sleep Apnea (OSA) Sympathetic Tone : Impact of APAP vs CPAP (APAP-CPAP)

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior., ResMed, Agir pour les maladies chroniques

The present study aims to compare muscle sympathetic neural activity by microneurography after one month treatment of fixed versus auto-adjusting CPAP treatment and its impact on arterial blood pressure

Background: Sleep apnea syndrome (SAS) currently affects 10% of general population. It is characterized by the occurrence during the sleep of the upper airways closure which cause repeated asphyxia. It is a public health problem due to its cardiometabolic complications. Indeed, the absence of SAS treatment increases cardiovascular mortality by 12% at 10 years. The main physiopathological mechanism is the activation of cardiovascular sympathetic control (the short-term regulation of blood pressure which bring in the sympathetic nervous system) An exposure to intermittent chronic hypoxia (caused by SAS) bring an increased of muscle sympathetic nerve activity (MSNA) contributing to elevated blood pressure Continuous Positive Airway Pressure (CPAP) can partly reduce this risk by decreasing elevation of blood pressure caused by the SAS. It has recently been demonstrated that all CPAP devices are not equivalent. Indeed, the auto-adjusted CPAP treatment induces a reduction in blood pressure lower than the reference treatment fixed CPAP. To this extent it is interesting to conduct a new randomized trial comparing these two treatments with vascular sympathetic tone. This will be assessed by peroneal microneurography recording. Objective: Compare Muscle Sympathetic Neural Activity (MSNA) by microneurography after one month of fixed versus auto-adjusted CPAP treatment in OSA patients naive from pressure therapy Methods: Prospective study, single-site, randomized, double-blind, parallel, one month controlled trial. After the diagnosis of sleep apnea, patients will be randomized for one month treatment with fixed ou auto-adjusting CPAP. Measurements of MSNA, heart rate variability and catecholamines will be held before and after treatment. An interim analysis will be performed after the inclusion of 24 patients based on group sequential design

Auto-CPAP changes the pressure delivered depending on events detected at any time (apnea, hypopnea …) and applies the lowest pressure required to eliminate events.

CPAP is a device that applies continous fixed positive pressure to the airways in order to keep them opened during sleep

Auto-adjusting CPAP is a device that applies auto-adjusting continous positive pressure to the airways in order to keep them opened during sleep

24h urine samples will be collected and acidified with acetic acid, stored at -20°C until analysis. Catecholamines (epinephrine, norepinephrine, and dopamine) will be measured in one milliliter of urine by high-performance liquid chromatography with electrochemical detection (Coularray Detector, ESA Dionex, Chelmsford, USA).

24h urine samples will be collected and acidified with acetic acid, stored at -20°C until analysis. Catecholamines (epinephrine, norepinephrine, and dopamine) will be measured in one milliliter of urine by high-performance liquid chromatography with electrochemical detection (Coularray Detector, ESA Dionex, Chelmsford, USA).

24h urine samples will be collected and acidified with acetic acid, stored at -20°C until analysis. Catecholamines (epinephrine, norepinephrine, and dopamine) will be measured in one milliliter of urine by high-performance liquid chromatography with electrochemical detection (Coularray Detector, ESA Dionex, Chelmsford, USA).

We will use these mathematical methods to analyze a signal over time: temporal analysis, Fourier transformation and wavelet transformation. High-frequency (HF) translates fluctuations in parasympathetic activity to cardiac destination, modulated by ventilatory characteristics (frequency, courant volume).

We will use these mathematical methods to analyze a signal over time: temporal analysis, Fourier transformation and wavelet transformation. Low frequency (LF) is classically considered to reflect the activity of the sympathetic system rather than the parasympathetic system.

Inclusion Criteria: patient with OSA (AHI ≥20 / h) patient with daytime sleepiness naive of any pressure treatment of OSA patient able to provide written informed consent not a vulnerable person or legally protected adult. Exclusion Criteria: pregnancy Person deprived of liberty or subject to a legal protection measure. Patient with serious heart failure (According to investigator judgment) patient with central sleep apnea index above 20% of AHI Patient with a significant intercurrent pathology that can influence the results. (According to investigator judgment).

Pepin JL, Tamisier R, Baguet JP, Lepaulle B, Arbib F, Arnol N, Timsit JF, Levy P. Fixed-pressure CPAP versus auto-adjusting CPAP: comparison of efficacy on blood pressure in obstructive sleep apnoea, a randomised clinical trial. Thorax. 2016 Aug;71(8):726-33. doi: 10.1136/thoraxjnl-2015-207700. Epub 2016 Apr 18.

Treptow E, Pepin JL, Bailly S, Levy P, Bosc C, Destors M, Woehrle H, Tamisier R. Reduction in sympathetic tone in patients with obstructive sleep apnoea: is fixed CPAP more effective than APAP? A randomised, parallel trial protocol. BMJ Open. 2019 Apr 4;9(4):e024253. doi: 10.1136/bmjopen-2018-024253.