The Role of Oxidative Stress in the Cardiovascular Consequences of Sleep Apnea

Rami Khayat

Status: Completed

Conditions: Sleep Apnea

Study type: Observational

Funder types: Other

Identifiers

NCT00701441

2005H0221

Details and patient eligibility

About

Obstructive Sleep Apnea (OSA) is the most common sleep disorder affecting up to 9-24 percent of middle aged adults, and is becoming increasingly implicated in the pathogenesis of hypertension, and other cardiovascular disorders. Up to half of patients with OSA have hypertension, and their risk of developing hypertension increases with the increasing severity of Sleep Apnea. Patients with OSA and no hypertension have endothelial dysfunction, which is believed to be the precursor for most cardiovascular disorders.

The upper airway collapse and obstruction that occur in OSA result in a pattern of intermittent hypoxia, that has been shown to be the cause of the hypertension, and endothelial dysfunction found in patients with OSA. Intermittent hypoxia results in oxidative stress, which in turn is linked to the pathogenesis of hypertension and endothelial dysfunction.

This protocol evaluates the role of the oxidative stress in endothelial function and blood pressure in patients with OSA. This is a pilot clinical study that will compare oxidative stress parameters, and endothelial function in patients with OSA before starting treatment with continuous positive airway pressure (CPAP) and 12 weeks post being on CPAP. These patients will be compared to control patients with no history of OSA. the study does not involve assignement to different treatments. All patients will receive the indicated treatment for OSA and measurements will be collected before and 12 weeks after adequate treatment.

Full description

Obstructive Sleep Apnea (OSA) is increasingly recognized as a cardiovascular risk factor. OSA is a cause of hypertension and has strong association with atherosclerosis, coronary heart disease, diabetes stroke , and fatal cardiovascular events. Endothelial dysfunction is a preclinical vascular abnormality that predicts subsequent development of vascular disease . Patients with OSA demonstrate endothelial dysfunction in the absence of any manifested vascular disease . The mechanism of endothelial dysfunction in OSA is largely unknown. Endothelial dysfunction in OSA is reversible with antioxidants, suggesting a role for oxidant overproduction in the decreased NO availability in OSA. This provides parallels to other cardiovascular diseases in which oxidative stress induced endothelial dysfunction is important.

Recent studies reported evidence of dysfunction or decreased expression of endothelial nitric oxide synthase (eNOS) in association with increased peroxynitrite in harvested venous endothelial cells of OSA patients. We endeavored to perform the first direct quantification of microvascular endothelial genes from OSA patients. We hypothesized that patients with OSA who are free of any cardiovascular disease will have early functional changes in the microcirculatory endothelial cells that are associated with OSA, and therefore would resolve with treatment. Given the role of oxidative stress in the vascular disease of OSA, we expected to find evidence of superoxide overproduction in the microcirculatory vessels. We expected these functional changes to be reversible with treatment of OSA.

Measurement of superoxide will be done on the subcutaneous biopsy tissue using quantitative Polymerase Chain Reaction (qPCR) and immunohistochemistry techniques and image analysis software. Measurement of endothelial function will be done using Doppler ultrasound.

Enrollment: 25 patients

Sex: All

Ages: 18+ years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Completed sleep study - Older than 18

Exclusion criteria

• Hypertension
• Diabetes
• coronary disease
• Peripheral vascular disease
• High cholesterol
• Smoking
• Pregnancy
• Use of erectile dysfunction medications or supplements

Trial design

25 participants in 2 patient groups

Control group: healthy individuals without OSA

Description:

healthy individuals without OSA who are matched in weight and age to the participating OSA patients

OSA group

Description:

Patients in the OSA group receive CPAP for 12 weeks as part of their care. patients with OSA provide measures at baseline and after 12 weeks of CPAP treatment.