Clinical Trial Phase IV Indication: Moderate-severe obstructive sleep apnea and dyslipidemia.

Objectives:

Main objective: To test whether 12 months of CPAP treatment associated with conventional pharmacological treatment improves the lipid profile of patients with dyslipidemia and moderate to severe OSA.

Secondary objectives:

• To test whether 12 months of treatment with CPAP associated with conventional pharmacological treatment improves serum uric acid concentration in patients with dyslipidemia and moderate-severe OSA.
• To determine the additional medium- and long-term effect of CPAP on insulin resistance in patients with dyslipidemia and moderate-severe OSA.
• To evaluate the impact of CPAP treatment on cardiovascular risk reduction in patients with dyslipidemia and moderate-severe OSA.
• To analyze the impact of supplemental CPAP treatment on glycemic control and C-reactive protein concentration in patients with dyslipidemia and moderate-severe OSA.
• To establish the impact of supplemental CPAP therapy on health-related quality of life in patients with dyslipidemia and moderate-severe OSA.
• To evaluate the effect of CPAP on inflammatory cytokines, oxidative stress biomarkers, sympathetic tone and intake-regulating hormones in patients with dyslipidemia and moderate-severe OSA.
• To relate CPAP-induced changes in serum lipid and uric acid concentration to changes in basal inflammatory response, oxidative stress, sympathetic activity, and intake-regulating hormones.
• To identify the subgroup of patients with dyslipidemia and moderate-severe OSA in whom 12 months of CPAP treatment achieves a more marked reduction in serum lipids and uric acid.

Design Randomized, parallel-group, nonblinded, controlled clinical trial with conventional treatment.

Study population Subjects aged 35 to 80 years with a diagnosis of dyslipidemia made at least six months ago and with moderate-severe obstructive sleep apnea (OSA) not requiring CPAP treatment according to conventional indications.

Sample size: 110 patients in each treatment arm.

Treatment Patients will be randomly assigned in a 1:1 ratio to one of the following treatment arms:

1. Conventional hygienic-dietary recommendations and promotion of daily physical activity.
2. Conventional hygienic-dietary recommendations and promotion of daily physical activity, plus treatment with positive airway pressure (CPAP).

Efficiency variables

• Main variables: LDL-cholesterol and uric acid.
• Total cholesterol, HDL-cholesterol and triglycerides.
• Basal blood glucose, glycosylated hemoglobin (HbA1c), creatinine and C-reactive protein.
• Systemic biomarkers: inflammatory (IL-6, IL-8 and TNF-α), oxidative stress (8-isoprostane), endothelial damage (endothelin, VCAM-1 and ICAM-1), sympathetic activity (neuropeptide Y) and appetite-regulating hormones (leptin, orexin A/hypocretin 1 and ghrelin).
• Clinical questionnaires: SF-12, EuroQoL, FOSQ and IPAQ.

Safety variables

• Clinical adverse event reporting.
• CPAP compliance (average hours of use per day).
• Epworth Sleepiness Questionnaire.
• Development of cardiovascular events.

Inclusion Criteria:

• Subjects from 35 to 80 years old
• Diagnosis of dyslipidemia. It will be considered as such, the existence of a previous clinical record of a diagnosis of dyslipidemia associated with treatment with lipidlowering agents, treatment with lipid-lowering agents or the presence of an altered blood test in the last two months, using the following cut-off points: total cholesterol ≥ 200 mg/dl, triglycerides ≥ 180 mg/dl, HDL-cholesterol ≤ 40 mg/dl or LDL-cholesterol ≥ 150 mg/dl.
• Moderate-severe sleep apnea, defined by AHI > 15 h-1 .

Exclusion Criteria:

• Predominance of central apneas-hypopneas, defined as more than 25% of total respiratory events.
• Patients with indications for CPAP treatment according to the International Sleep Consensus: hypertensive, excessive daytime sleepiness (Epworth Sleepiness Scale > 11) or impaired sleep-related quality of life considered relevant by their regular physician.
• Professional drivers, at-risk profession or respiratory insufficiency (according to criteria of the clinical pathway for the diagnosis and treatment of sleep-disordered breathing).
• Pretreatment with CPAP