Impact of Statin Therapy on Adaptations to Aerobic Exercise

High cholesterol and cardiovascular disease (CVD) is currently prevented and treated with
statin therapy. Statin use can cause muscle weakness, fatigue and/or pain, and these symptoms
can increase with dose and duration of statin use. Statins may also change the ability to
exercise.

This study is testing how different doses of a statin, Lipitor, affect muscle health and
exercise. The doses that will be used in this study (20 mg/day or 80 mg/day) are typical for
treating high cholesterol.

This study is expected to last about 14 weeks.

Inclusion Criteria:

- Body Mass Index (BMI) between 25-43 kg^m2

- Sedentary (less than 30 min of physical activity/week during last 6 months and less
than 7,500 steps/day measures by pedometer at baseline)

- Weight stable (no more than 5% change in body weight the previous 3 months)

- >5% risk for a cardiovascular event in the next 10 years according to the 2013
American College of Cardiology/American Heart Association risk calculator

- Stable doses of medications for 90 days

- Willing to stop all Nonsteroidal Antiinflammatory Drugs (NSAIDs) and aspirin for 7
days prior to muscle biopsy

Exclusion Criteria:

- Smoking

- Use of statins in the last 6 months

- Use of other medications or supplements that affect lipid profiles or body weight in
the last 6 months (e.g., fibric acids, bile acid sequestrants, nicotinic acids, fish
oil)

- Diagnosis of chronic diseases including cardiovascular (CVD), diabetes, other
metabolic diseases (e.g., thyroid), cancer, HIV, or acquired immunodeficiency syndrome

- History of abnormal bleeding problems

- Currently taking (within the last 10 days) anti-platelet medication (Plavix),
Warfarin, and other anti-coagulants (eliquis, pradaxa, and xarelto) medications

- >2 fold upper normal limit (UNL) for alanine aminotransferase (ALT) or creatinine

- Women who are pregnant or breastfeeding

- Individuals with polymorphisms known to be associated with susceptibility for statin
induced myopathies (tested at screening)

- Currently enrolled in another research study