The Effects of Obesity and Obstructive Sleep Apnea on Inflammation and Heart Disease

OSA is a common sleep disorder that is characterized by a brief collapse of the upper airway
during sleep. This blockage prevents air from flowing properly into the lungs and causes
pauses in breathing. If left untreated, OSA can cause high blood pressure, memory problems,
weight gain, impotency, and headaches. It is also associated with an increased risk of
inflammation-related heart conditions. Obesity is common among individuals with OSA and it
may also be associated with inflammation. It is not known, however, whether the increased
risk of heart problems is caused primarily by the inflammatory effects of OSA or obesity.

The most common treatment for OSA is continuous positive airway pressure (CPAP) therapy, in
which a mask is worn over the nose during sleep. Air flows through the mask to maintain a
level of pressure that keeps the throat open. The most common treatment for obesity is
weight loss. This study will determine the primary cause of heart-related inflammation by
evaluating the individual and combined effects of CPAP therapy and a weight loss program in
treating obese individuals with OSA. The study will also determine the independent effects
of these therapies on insulin resistance and blood vessel function (arterial stiffness,
central arterial pressures).

This study will enroll obese individuals with moderate to severe OSA for a total of 24
weeks. Potential participants will first take part in an overnight sleep study at the
University of Pennsylvania sleep lab. Sensors will monitor body functions during the night,
including brain and muscle activity, eye movement, heart rate, breathing effort, air flow,
and blood oxygen levels. Eligible participants will then be randomly assigned to CPAP
therapy, a weight loss program, or a combination of the two. Participants in the weight loss
program will receive weekly dietary counseling and will be encouraged to decrease caloric
intake and increase physical activity. Participants receiving CPAP therapy will use a CPAP
machine each night while they sleep. Study visits for all participants will occur at
baseline and Weeks 6, 12, and 24. Blood will be collected to measure levels of
triglycerides, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL)
cholesterol, and levels of C-reactive protein (CRP), which is an inflammation biomarker.
Insulin resistance will be evaluated using a glucose tolerance test, and blood vessel
function will be evaluated using a brachial artery reactivity test in which artery size and
blood flow will be measured with an ultrasound.