The purpose of this study is to test how different doses of a statin, Lipitor, affect muscle health and function, and cardiovascular fitness.

Inclusion Criteria:

• Body mass index (BMI) between 25-43
• 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 and/or 2 out of 5 metabolic syndrome risk factors (Triglycerides ≥ 150 mg/dL; HDL ≤ 40 mg/dL; Glucose ≥ 100mg/dL; Waist Circumference ≥ 102cm for males, 88cm for females; Blood pressure: ≥ 130mmHg systolic and/or 85mmHg diastolic or being treated for hypertension) and/or LDL-Cholesterol >120 mg/dl.
• 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
• Previous use of statins
• 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 CVD, other metabolic diseases (e.g., thyroid), current diagnosis and active treatment of cancer, HIV, or acquired immunodeficiency syndrome.
• Diagnosis of type 1 or type 2 diabetes at the time of screening (fasting blood glucose >126mg/dL). If evidence of type 2 diabetes outcome measures is detected during the course of the study (fasting glucose > 126 mg/dl or HbA1c > 6.5%) we will notify the participant to contact their physician.
• 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 (SLCO1B1 and GATM) known to be associated with susceptibility for statin induced myopathies (tested at screening)
• Currently enrolled in another research study

Participants were contacted weekly by phone or email and prompted to disclose any adverse events. Additional adverse events could be reported if participant contacted study team outside of the usual weekly check in. Adverse events were monitored until symptoms subsided or adverse event ended or until the end of the 12 month intervention period.

The definitions used for adverse events and/or serious adverse events are the same as clinicaltrials.gov definitions

The COVID-19 epidemic started in the middle of the trial forcing us to stop recruitment for four months. Furthermore, the continuation of the pandemic slowed recruitment for the rest of the trial and significantly impacted n size. There was also a national dextrose shortage following a hurricane in Puerto Rico. As a result many of the IVGTT were not conducted.