Pharmacogenomic Modulators of Impaired Exercise Adaptation in Statin Users

Pharmacogenomic Modulators of Impaired Exercise Adaptation in Statin Users

3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) have beneficial effects (prevent stroke, heart attack) but also some bad ones (block some good effects of exercise). Individuals have genetic variations in proteins that metabolize/transport statins. The investigators hypothesize that these variations modulate the relationship between statin use and lack of benefit from exercise. The investigators will test this by having statin-users do supervised exercise for 6 weeks, measuring the cardiorespiratory fitness before/after and correlating this to genetic variations present in the participant.

Inclusion Criteria:

• English-speaking
• Adults (aged 35-65 years)
• Overweight or obese (body-mass index [BMI] 25-43)
• Currently taking high-dose atorvastatin (40-80mg once daily) for primary prevention of cardiovascular disease and/or stroke
• Sedentary (<30 minutes of structured exercise weekly)
• Willing to participate in supervised exercise three times weekly
• Willing to not make intentional changes to their diet during the study period.

Exclusion Criteria:

• Tobacco smokers
• Pregnant or breastfeeding
• Use other medications that affect lipid metabolism (e.g. fibric acid, fish oil)
• Markedly functional debilitated and unable to exert 4 metabolic equivalents (METs) of energy (e.g. unable to climb a flight of stairs without stopping), or who have
• Been advised by a physician to avoid exercise due to comorbid serious cardiovascular disease
• Uncontrolled diabetes (A1c > 8)
• Uncontrolled thyroid disease
• HIV/AIDS
• Cancer
• History of myocardial infarction or stroke
• History of statin-induced myopathy.