HMG-CoA Reductase Inhibitor Toxicity
Conditions
Brief summary
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.
Interventions
OTHERExercise
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.
Sponsors
University of Kansas Medical Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
35 Years to 65 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Peak oxygen consumption (VO2max) | 6 weeks | Change pre/post intervention; compared with genomic variants |
Secondary
| Measure | Time frame |
|---|---|
| Weight | 6 weeks |
| Resting heart rate | 6 weeks |
| Resting systolic blood pressure | 6 weeks |
Countries
United States
Outcome results
None listed