Pharmacogenomic Modulators of Impaired Exercise Adaptation in Statin Users

Purpose

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.

Condition

  • HMG-CoA Reductase Inhibitor Toxicity

Eligibility

Eligible Ages
Between 35 Years and 65 Years
Eligible Genders
All
Accepts 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.

Study Design

Phase
N/A
Study Type
Interventional
Allocation
N/A
Intervention Model
Single Group Assignment
Primary Purpose
Basic Science
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Single arm
  • Other: Exercise
    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.

Recruiting Locations

University of Kansas Medical Center
Kansas City, Kansas 66160
Contact:
Daniel J Parente, MD PhD

More Details

Status
Unknown status
Sponsor
University of Kansas Medical Center

Study Contact

Daniel J Parente, MD PhD
9139458054
dparente@kumc.edu