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Potential Mechanism of Exercise Impairment in OSA

3 januari 2018 bijgewerkt door: Robert L. Owens, University of California, San Diego

Pulmonary Vasoreactivity as a Potential Mechanism of Exercise Impairment in Obstructive Sleep Apnea

Obstructive sleep apnea (OSA) is a common disorder with major cardiovascular sequelae. A recent study confirmed that OSA is associated with impaired exercise capacity and increasing OSA severity predicts worsening exercise capacity, which is a marker of potential increased cardiovascular risk. However, potential mechanisms of decreased exercise capacity caused by OSA remain unclear. Several pathophysiologic mechanisms of OSA have been proposed and investigators hypothesize that endothelial dysfunction leading to exercise-induced right ventricular dysfunction and associated pulmonary hypertension is the potential mechanism for impaired exercise capacity in OSA.

Studie Overzicht

Toestand

Voltooid

Conditie

Obstructieve slaapapneu

Gedetailleerde beschrijving

Obstructive sleep apnea (OSA) is a common disorder with major cardiovascular sequelae, including increased systemic hypertension and strokes. OSA is highly prevalent among patients with cardiovascular disease (CVD), but OSA remains under-diagnosed, thus under-treated. Furthermore, a recent study confirmed that OSA is associated with impaired exercise capacity and increasing OSA severity predicts worsening exercise capacity, which is a marker of potential increased cardiovascular risk. However, potential mechanisms of decreased exercise capacity caused by OSA remain unclear.

Several pathophysiologic mechanisms of OSA have been proposed to explain this observation. Endothelial dysfunction is one mechanism that may result from OSA-related intermittent hypoxemia, heightened sympathetic activation, and increased blood pressure. Endothelial dysfunction is characterized by alteration of normal endothelial physiology consisting of a reduction in the bioavailability of vasodilators such as nitric oxide leading to impaired endothelium-depended vasodilation. Endothelial dysfunction has been consistently associated with an increased incidence of CVD. Recent evidence also suggests a correlation between endothelial function and exercise capacity.

In addition, endothelial dysfunction of pulmonary vasculature play an integral role in the pathogenesis of pulmonary hypertension (PH), which is defined by a mean pulmonary artery pressure exceeding 25 mm Hg. PH is associated with increased mortality and multiple morbidities including impaired exercise capacity. OSA has been formally recognized as a cause of PH by the World Health Organization (WHO) and the estimated prevalence of PH in patients with OSA is 17%. Repetitive nocturnal hypoxemia, increased sympathetic tone, and diminished endothelial dependent vaso-reactivity contribute to pulmonary artery hypoxic vasoconstriction, subsequently leading to pulmonary vasculature remodeling and PH. Recently, PH induced by exercise was described as part of the PH spectrum and may represent early, mild, PH that is still clinically relevant in many patients. To detect early PH in OSA patients may signify the importance of treatment and compliance for newly diagnosed OSA patients.

In summary, our hypothesis is that OSA patients may have endothelial dysfunction that leads to impaired exercise capacity via exercise-induced pulmonary hypertension. If our hypothesis is correct, non-invasive measurements of endothelial function could be used clinically to risk stratify patients or follow response to treatment.

Studietype

Observationeel

Inschrijving (Werkelijk)

Contacten en locaties

In dit gedeelte vindt u de contactgegevens van degenen die het onderzoek uitvoeren en informatie over waar dit onderzoek wordt uitgevoerd.

Studie Locaties

Verenigde Staten
- California
  - San Diego, California, Verenigde Staten, 92093
    - University of California, San Diego

Deelname Criteria

Onderzoekers zoeken naar mensen die aan een bepaalde beschrijving voldoen, de zogenaamde geschiktheidscriteria. Enkele voorbeelden van deze criteria zijn iemands algemene gezondheidstoestand of eerdere behandelingen.

Geschiktheidscriteria

Leeftijden die in aanmerking komen voor studie

30 jaar tot 65 jaar (Volwassen, Oudere volwassene)

Accepteert gezonde vrijwilligers

Geslachten die in aanmerking komen voor studie

Allemaal

Bemonsteringsmethode

Kanssteekproef

Studie Bevolking

Investigators will enroll 30 subjects with OSA (OSA group) and 30 subjects without OSA (control group). The detailed inclusion and exclusion criteria for subjects are listed below. Female subjects will be offered a urinary pregnancy test and only those documented to be non-pregnant will be studied.

Beschrijving

Inclusion Criteria:

BMI < 30
OSA group: diagnosis of untreated moderate-to-severe OSA (apnea-hypopnea index (AHI) ≥ 15 events/h).
Control group: no OSA (AHI < 5 events/h).

Exclusion Criteria:

Currently using Continuous Positive Airway Pressure (CPAP) or oral appliance treatment for OSA
Uncontrolled cardiac co-morbidity, e.g. ischemic heart disease, heart failure, or valvular heart disease that would prevent exercise
Uncontrolled pulmonary co-morbidity, e.g. asthma or chronic obstructive pulmonary disease (COPD)
Comorbidities that may severely impair peripheral circulation, e.g. uncontrolled diabetes mellitus, or systemic scleroderma
Neurological conditions limiting the ability to perform walking or cycling
Orthopedic condition limiting the ability to perform walking or cycling
Current smokers, alcohol (> 3 oz/day) or use of illicit drugs.
Psychiatric disorder, other than mild and controlled depression; e.g. schizophrenia, bipolar disorder, major depression, panic or anxiety disorders.
Pregnancy

Studie plan

Dit gedeelte bevat details van het studieplan, inclusief hoe de studie is opgezet en wat de studie meet.

Hoe is de studie opgezet?

Ontwerpdetails

Aantal groepen / cohorten

Cohorten en interventies

Groep / Cohort
OSA Group Apnea-hypopnea index (AHI) ≥ 15 events/h
Control Group Apnea-hypopnea index (AHI) < 5 events/h

Wat meet het onderzoek?

Primaire uitkomstmaten

Uitkomstmaat	Maatregel Beschrijving	Tijdsspanne
Endothelial function, as measured by endoPAT, between OSA patients and matched healthy controls Tijdsspanne: Baseline	EndoPAT is a non-invasive measurement of endothelial function, using peripheral arterial tonometry. Exercise tolerance is measured by Cardiopulmonary exercise testing (CPET). Effects of OSA on exercise tolerance and endothelial function will be evaluated.	Baseline

Secundaire uitkomstmaten

Uitkomstmaat	Maatregel Beschrijving	Tijdsspanne
Right ventricular systolic pressure (RVSP) in response to exercise Tijdsspanne: Baseline	Measured by Echocardiogram, between OSA patients and matched healthy controls	Baseline
Pulmonary systolic pressure (PASP) in response to exercise Tijdsspanne: Baseline	Measured by Echocardiogram, between OSA patients and matched healthy controls	Baseline
Right ventricular outflow track (RVOT) peak velocity in response to exercise Tijdsspanne: Baseline	Measured by Echocardiogram, between OSA patients and matched healthy controls	Baseline
Velocity time interval (VTI) in response to exercise Tijdsspanne: Baseline	Measured by Echocardiogram, between OSA patients and matched healthy controls	Baseline
Pulmonary artery acceleration time in response to exercise Tijdsspanne: Baseline	Measured by Echocardiogram, between OSA patients and matched healthy controls	Baseline
Systolic peak tricuspid myocardial annular velocity Tijdsspanne: Baseline	Measured by Echocardiogram, between OSA patients and matched healthy controls	Baseline
Diastolic peak tricuspid myocardial annular velocity Tijdsspanne: Baseline	Measured by Echocardiogram, between OSA patients and matched healthy controls	Baseline
Peak tricuspid myocardial annular velocity during isovolumic contraction Tijdsspanne: Baseline	Measured by Echocardiogram, between OSA patients and matched healthy controls	Baseline
Peak tricuspid myocardial annular velocity during isovolumic relaxation Tijdsspanne: Baseline	Measured by Echocardiogram, between OSA patients and matched healthy controls	Baseline
Right ventricular (RV) wall stress Tijdsspanne: Baseline	Measured by Echocardiogram, between OSA patients and matched healthy controls	Baseline
3-D right ventricular ejection fraction (3D-RVEF) Tijdsspanne: Baseline	Measured by Echocardiogram, between OSA patients and matched healthy controls	Baseline
Systolic peak right ventricular (RV) strain Tijdsspanne: Baseline	Measured by Echocardiogram, between OSA patients and matched healthy controls	Baseline
Early diastolic peak right ventricular (RV) strain Tijdsspanne: Baseline	Measured by Echocardiogram, between OSA patients and matched healthy controls	Baseline
Late diastolic peak right ventricular (RV) strain Tijdsspanne: Baseline	Measured by Echocardiogram, between OSA patients and matched healthy controls	Baseline

Medewerkers en onderzoekers

Hier vindt u mensen en organisaties die betrokken zijn bij dit onderzoek.

Sponsor

University of California, San Diego

Studie record data

Deze datums volgen de voortgang van het onderzoeksdossier en de samenvatting van de ingediende resultaten bij ClinicalTrials.gov. Studieverslagen en gerapporteerde resultaten worden beoordeeld door de National Library of Medicine (NLM) om er zeker van te zijn dat ze voldoen aan specifieke kwaliteitscontrolenormen voordat ze op de openbare website worden geplaatst.

Bestudeer belangrijke data

Studie start

1 juli 2015

Primaire voltooiing (Werkelijk)

9 mei 2017

Studie voltooiing (Werkelijk)

9 mei 2017

Studieregistratiedata

Eerst ingediend

12 juli 2015

Eerst ingediend dat voldeed aan de QC-criteria

20 juli 2015

Eerst geplaatst (Schatting)

22 juli 2015

Updates van studierecords

Laatste update geplaatst (Werkelijk)

5 januari 2018

Laatste update ingediend die voldeed aan QC-criteria

3 januari 2018

Laatst geverifieerd

1 januari 2018

Meer informatie

Termen gerelateerd aan deze studie

Trefwoorden

Aanvullende relevante MeSH-voorwaarden

Andere studie-ID-nummers

UCSD150468

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