Statins and CPAP in Adipose Tissue of OSA

In recent years the role adipose tissue to the development of cardiometabolic disorders has been increasingly recognized. Dysfunctional adipose tissue is an important source for systemic inflammation, AngII, and FFA, thus increasing CV risk in obese and aging populations. Even though heightened cardiovascular risk in OSA patients is acknowledged, adipose tissue from OSA patients has not been investigated.

CPAP is standard therapy for OSA, but has shown mixed results for improvement of vascular function, insulin sensitivity, and BP, and does not reduce CV events and mortality, even in patients with established CV disease. Hence, eliminating IH alone may not be sufficient to repair preexisting damage; additional adjunct strategies aimed at cellular repair may be required to reduce cardiometabolic burden and CV risk. Statins have pleiotropic effects including reducing inflammation, and improving BP. The aim of this study is to examine the longitudinal changes in the cellular and molecular composition of adipose tissue in OSA subjects in response to 6 months combination therapy of CPAP and atorvastatin. We hypothesize that the combination therapy will reduce adipose tissue cellular damage (p16INK4A+γ-H2AX dual positive cells). Also, decreases in adipose tissue cellular damage will be associated with improved cardiometabolic profile. These studies will provide pivotal insights into potential therapeutic strategies which may reduce cardiometabolic burden in OSA population.

Inclusion criteria

• Participated in IRB 17-003825
• Apnea hypopnea index, AHI/RDI ≥10, or AHI/RDI >5 with significant nocturnal hypoxemia documented by a fall in oxygen saturation to 90% or below.
• Women of child-bearing age will be allowed to participate if they agree to use acceptable birth control during the study period.
• TSH levels in range of 0.3-6 mIU/L (TSH above 6 mIU/L will be allowed if free thyroxine (free T4) is within normal range)

Exclusion criteria

• Elevated ALT (>3 times upper normal limit)
• Fasting glucose >120 mg/dL and/or HbA1c ≥ 6.5 %
• Females planning to be pregnant in next six months will not be included in the study
• Known serious or hypersensitivity to HMG-CoA reductase inhibitors.
• Alcohol consumption >3 units/day