Obstructive Sleep Apnea (OSA), Hypertension , β1 Subunit of Maxi-k+ Channel and Cardiovascular Risk (OSAS)

This study has been completed.
Sponsor:
Collaborator:
Beca de Excelencia de la CICE de la Junta de Andalucia y programa Operativo FEDER de Andalucia
Information provided by (Responsible Party):
Angeles Sanchez Armengol, Sociedad Española de Neumología yu Cirugía Torácica
ClinicalTrials.gov Identifier:
NCT01791270
First received: February 12, 2013
Last updated: June 20, 2013
Last verified: June 2013

February 12, 2013
June 20, 2013
February 2010
December 2011   (final data collection date for primary outcome measure)
Improvement in blood pressure parameters, in vascular endothelial function and in levels of β1 subunit expression of Maxi-K + channel in patients with OSA after treatment with CPAP [ Time Frame: 3 months ] [ Designated as safety issue: No ]

Primary Outcome Measure: Look at the difference in OSA and control subjects between the parameters that measure blood pressure in AMBP, the reactive hyperemia test for ischemia flowmetry technique and the expression levels of ß1 subunit of the Maxi-K + channel in peripheral blood leukocytes.

In OSA group patients after three months of correct treatment with CPAP, the goal is to find:

  • Improvement in blood pressure parameters (ambulatory blood pressure).
  • Improved parameters expressing vascular endothelial function at subclinical level (recorded by laser-Doppler flowmetry).
  • Improvement in levels of β1 subunit expression of Maxi-K + channel in peripheral blood leukocytes (basic).
Same as current
Complete list of historical versions of study NCT01791270 on ClinicalTrials.gov Archive Site
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Obstructive Sleep Apnea (OSA), Hypertension , β1 Subunit of Maxi-k+ Channel and Cardiovascular Risk
Expression of Maxi-k+ Channel β1 Subunit in Peripheral Leukocytes, Blood Pressure Values and the Presence of Endothelial Dysfunction in Patients With Obstructive Sleep Apnea

To describe the relationship between OSA and clinical Hypertension (performing ABPM), endothelial dysfunction (performing flowmetry), and its relation at the basic research (determining the β1 subunit in Peripheral Leukocytes in peripheral blood). This relation between OSA and HTA has been evaluated in basal conditions and after modifying the pathophysiological role of OSA applying treatment with positive continues pressure (CPAP) during 3 months.

Background: Several epidemiological studies have demonstrated that untreated OSA with continuous positive airway pressure, is related to high rates of cardiovascular morbidity and mortality, being HTA the most important cardiovascular morbidity associated with OSA. This relationship has been studied at three levels: clinical, subclinical and the basic research or molecular level. Most patients with OSA diagnosis have developed clinical hypertension and, because of the high prevalence of nocturnal hypertension in OSA, it would be essential to monitor blood pressure during sleep, using this device ambulatory blood pressure monitoring (ABPM). Regard to endothelial dysfunction, which can exist before irreversible vascular changes have occurred in the arterial wall (subclinical level) has been reported that patients with OSA have lower blood flow (measured by arterial flowmetry) and after treatment with CPAP, there is an improvement in endothelial function. At basic research level, in previous studies it has been observed that hypoxia down regulates the expression of Maxi-K+ Channel B1-subunit in smooth muscle cell and also in peripheral leukocytes. This channel is involved in the regulation of arterial vasodilation, being β1 subunit responsible for the vascular tone regulation. Basic research studies have shown the relationship between hypertension and ß1 subunit, describing that the expression of that unit decreases in hypertensive animal models. In a pilot study in OSA patients was suggested that ß1 subunit channel Maxi-K + could play an important role in vascular dysregulation of these patients. It has been also described a correlation between ß1 subunit level in vascular smooth muscle cells and its level in leukocytes.

Objective: To describe the relationship between OSA and hypertension from a clinical point of view (by performing ABPM), its relationship with endothelial dysfunction (by performing a flowmetry) and basic research level (by the determination of β1 subunit of the maxi-K channel +). This relationship between hypertension and OSA has been assessed at baseline condition in a group of OSA patients and a control group without OSA, and after changing the pathophysiological role of OSA treating with continuous positive pressure airway (CPAP) in the group of OSA patients.

Patients: Prospective study in which:

  1. - We compared 61 patients with sleep apnea-hypopnea syndrome and 19 control subjects without OSA.
  2. - In the group of 61 patients with OSA: we compared the results before and after three months of correct treatment with CPAP.

Measurements:

  1. - Respiratory Polygraphy
  2. - Ambulatory Blood Pressure Monitoring
  3. - Endothelial dysfunction, by determining the hyperaemic response to ischemia using a Laser-Doppler flowmeter.
  4. - ß1en subunit expression in peripheral blood leukocytes.

These procedures are described below:

  1. - Respiratory Polygraphy:

    -Nocturnal cardiorespiratory polygraphy was performed in the "sleep laboratory of Medical-Surgical Unit of Respiratory Diseases". It has used a respiratory polygraph "Sibelhome plus"(trade name).

    We measured the following variables:

    • Oronasal Flow.
    • Snore: using laryngotracheal microphone.
    • Thoracoabdominal-Effort: by two bands effort sensors placed at the level of the chest and abdomen.
    • Arterial oxygen saturation (SaO2): Flexible digital pulse oximeter.
    • Body-position sensor.

    The records are stored in a specific database and analysis was carried out manually. The events are defined

    • Apnea: absence of oronasal airflow for ≥ 10 sec.
    • Hypopnea: oronasal flow decrease ≥ 50% from baseline for ≥ 10 seconds, accompanied by desaturation.

    We calculated the following parameters:

    • AHI: total number of apnea + hypopnea / hour check. When AHI is <5 was considered negative for OSA and when AHI WAS ≥ 15, OSA diagnosis was made.
    • Desaturation index (DI): total number of desaturations / hour check.
    • Basal and minimum-Saturation: automatic analysis obtained oximetry throughout the entire record.
    • Percentage of recording time with SaO2 <90% (CT90): automatic analysis obtained oximetry throughout the entire record.
  2. - Ambulatory Blood Pressure Monitoring: The dispositive measures blood pressure automatically every 20 minutes for 24 hours. The records were obtained on a weekday and when the patient worked in shifts, it was made when the patients didn´t work at night.

    We collected the following variables:

    • 24hours systolic and diastolic blood pressure.
    • Medium blood pressure at day and night.
    • Standard deviation day and night blood pressure.
    • Percentage of high measured for 24 hours, and during periods of activity and rest.
    • BP variability (standard deviation of the mean).
    • 24-hour mean heart rate.
    • Average heart rate daytime.
    • Night Average heart rate.
  3. - Endothelial dysfunction, by determining the hyperaemic response to ischemia using a Laser-Doppler flowmeter: The subject lay on the bed, and kept quiet 15-20 minutes. A cuff blood pressure measurement (uninflated) was placed on the arm and laser-Doppler device in the forearm. During 15 minutes the system measured basal situation and after that the cuff rapidly swelled over 20mmHg of the systolic blood pressure during for 4 minutes. During this period the system monitor showed perfusion units and at the end of this period the cuff was suddenly deflated and the monitor revealed a rise above the pre-ischemia in perfusion units.

    The software performed two types of analysis:

    • General analysis: where reported the initial value, maximum value, percentage change from the first to last value or maximum slope of the curve or slope and area under the curve.
    • Adjusted Analysis: It was estimated biological zero, peak flow, hyperemia area, time to maximum hyperemia, time to reach the half-maximal hyperemia and latency.
  4. - ß1 subunit expression in peripheral blood leukocytes: Performing the level of β1 subunit of Maxi-K + channel expression in peripheral blood leukocytes. Extraction total RNA from leukocytes following the instructions QIAamp RNA Blood Mini kit.

From these cells was performed the expression level of β1 subunit by quantitative RT-PCR technique. For reverse transcription of RNA using the Superscript III First-kit Starnd Synthesis System (trade name). For quantitative PCR we used the ABI PRISM equipment 7500 Sequence Detection System (Applied Biosystems), using the reagents Sybr Green PCR Master Mix or TaqMan probes, following the protocols indicated by the manufacturer.

Observational
Observational Model: Case Control
Time Perspective: Prospective
Not Provided
Retention:   Samples Without DNA
Description:

Periferical blood

Non-Probability Sample

Group of OSA patients and a control group without OSA

Obstructive Sleep Apnea
Device: Continuous positive airway pressure (CPAP) therapy

Device: CPAP accordingly to the normal therapy in daily practice. In the group of 61 patients with OSA: we compared the results before and after three months of correct treatment with CPAP.

First, an automatic continuous positive airway pressure device (autoCPAP REMstar) was used to evaluate the pressure titration by night registration at patient home. AutoCPAP gets complete information about the optimum level to be set as therapeutic (CPAP pressure).

The patient has been reevaluated periodically in the outpatient Sleep Unit to verify proper adaptation and compliance of CPAP.

We considered a proper compliance when patients used CPAP ≥ 4 hours/day. This data has been extracted from the counter included in the CPAP compressor.

Procedures:

  1. - Respiratory Polygraphy
  2. - Ambulatory Blood Pressure Monitoring
  3. - Endothelial dysfunction, by determining the hyperaemic response to ischemia using a Laser-Doppler flowmeter.
  4. - ß1en subunit expression in peripheral blood leukocytes.
  • OSA versus Control subjects.
    sleep apnea-hypopnea syndrome and control
  • OSA patients before and after treatment, CPAP
    Continuous positive pressure CPAP
    Intervention: Device: Continuous positive airway pressure (CPAP) therapy
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
80
December 2012
December 2011   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • The control group was defined as "absence of OSA"(apnea-hypopnea index (AHI) in cardiorespiratory polygraphy <5).
  • The "OSA" group was defined as OSA symptoms + an AHI ≥ 15 in cardiorespiratory polygraphy

Exclusion criteria:

  • Awaking hypoxemia (PO2 in arterial blood gas <70 mmHg) or arterial saturation <90% in digital pulse oximetry.
  • Treated hypertensive patients who were not well controlled at the time of inclusion: change of HTA treatment in the previous 3 months.
Both
18 Years to 75 Years
Yes
Contact information is only displayed when the study is recruiting subjects
Not Provided
 
NCT01791270
P09-CTS-4971
No
Angeles Sanchez Armengol, Sociedad Española de Neumología yu Cirugía Torácica
Angeles Sanchez Armengol
Beca de Excelencia de la CICE de la Junta de Andalucia y programa Operativo FEDER de Andalucia
Principal Investigator: Angeles Sánchez Armengol, Md PhD Hospitales Universitarios Virgen del Rocío
Sociedad Española de Neumología y Cirugía Torácica
June 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP