Pharmacogenomic Modulators of Impaired Exercise Adaptation in Statin Users

Study Overview
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Brief Summary
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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.

Official Title
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Pharmacogenomic Modulators of Impaired Exercise Adaptation in Statin Users

Conditions
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HMG-CoA Reductase Inhibitor Toxicity

Intervention / Treatment
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* Other: Exercise


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 35 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Single arm<br> | Other: Exercise<br>* Patients will exercise on a treadmill three times weekly at approximately 60% VO2max for 30 minutes (week one) followed by 45 minutes (week two and thereafter) for a total of 6 seeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Peak oxygen consumption (VO2max) | Change pre/post intervention; compared with genomic variants | 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Resting heart rate |  | 6 weeks | 
| Resting systolic blood pressure |  | 6 weeks | 
| Weight |  | 6 weeks |