Dyslipidemia, Endurance Training, Long-Distance Running, Statin-Associated Muscle Symptoms
Conditions
Brief summary
Statins lower low-density lipoprotein cholesterol (LDL-C) and help prevent atherosclerotic cardiovascular disease, but some users develop statin-associated muscle symptoms (SAMS) such as soreness, stiffness, weakness, or elevated creatine kinase (CK). These symptoms may be more noticeable during exercise. Regular long-distance running improves cardiopulmonary fitness-VO₂max, aerobic threshold (AT), and respiratory compensation point (RCP)-mainly through mitochondrial and metabolic adaptations. Prior studies suggest that lipophilic statins like simvastatin may blunt these adaptations, while hydrophilic statins such as rosuvastatin may have a smaller impact. However, prospective data in habitual endurance runners are limited. This randomized controlled trial will examine how rosuvastatin affects cardiopulmonary fitness improvements and muscle tolerance in individuals who run at least three times per week and meet clinical criteria for statin therapy. After informed consent and baseline cardiopulmonary exercise testing (CPET), participants will be randomized to rosuvastatin 10 mg daily or no statin therapy for three months. Both groups will maintain their usual training routines, and training load will be recorded using heart-rate-based TRIMP. CPET will be repeated monthly to assess changes in VO₂max, AT, and RCP, and muscle enzymes and SAMS will be evaluated at each visit. The study aims to clarify whether rosuvastatin influences endurance-related physiological adaptations or increases muscle symptoms in regular long-distance runners.
Interventions
DRUGRosuvastatin
Rosuvastatin 10 mg tablet taken orally once daily at bedtime for 3 months.
Sponsors
Taipei Medical University WanFang Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Age ≥ 18 years. * Meets clinical criteria for statin therapy, including at least one of the following: * Family history of hyperlipidemia. * LDL-C ≥ 160 mg/dL. * 10-year Atherosclerotic Cardiovascular Disease (ASCVD) risk ≥ 7.5% * Diabetes mellitus with LDL-C ≥ 70 mg/dL. * Determined by a clinician to require lipid-lowering therapy. * Currently using or eligible to initiate rosuvastatin therapy. * Performs long-distance running at least 3 times per week and is willing to maintain regular training for 3 months. * Able and willing to undergo cardiopulmonary exercise testing (CPET) and to record training data using a sports watch (for TRIMP calculation). * No known drug allergies and provides written informed consent after study explanation.
Exclusion criteria
* Known allergy or intolerance to statins or rosuvastatin. * History of severe statin-related adverse events, including rhabdomyolysis or marked creatine kinase (CK) elevation. * Liver dysfunction with AST or ALT \> 3× upper limit of normal. * Moderate to severe renal impairment (eGFR \< 30 mL/min/1.73 m²). * Current lower-limb pain, tendon injury, or other conditions that prevent running training. * Not suitable for maximal cardiopulmonary exercise testing (CPET), such as unstable angina, uncontrolled hypertension, or recent cardiovascular events. * Pregnant or breastfeeding. * Inability to comply with study procedures, including use of a sports watch, regular follow-up visits, or maintaining running training.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| VO₂max (mL/kg/min) | Baseline (Month 0), Month 1, Month 2, Month 3 | Maximum oxygen consumption obtained from cardiopulmonary exercise testing (CPET). Used to assess changes in cardiopulmonary fitness over the 3-month intervention period. |
| Aerobic Threshold (AT) | Baseline, Month 1, Month 2, Month 3 | Aerobic threshold determined by standardized CPET. Represents the transition from aerobic to anaerobic metabolism during exercise. |
| Respiratory Compensation Point (RCP) | Baseline, Month 1, Month 2, Month 3 | RCP measured via CPET, representing the ventilatory response to metabolic acidosis. Used to evaluate endurance training adaptation. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Calculated Training Load Score (using TRIMP method) | Through the end of the 3-month intervention period | Training load is reported as a single Training Impulse (TRIMP) score. It is calculated by multiplying exercise duration (minutes) by a heart-rate-based intensity factor (e.g., fractional heart rate reserve). This integrates two metrics into one unified numerical value. The formula is: TRIMP = Duration (min) x \[ΔHR ratio\] x y Where: ΔHR ratio = (HR\_ex - HR\_rest) / (HR\_max - HR\_rest) y = A weighting factor derived from an exponential function to account for the disproportionate increase in physiological strain at higher exercise intensities (using gender-specific constants: 0.64e\^(1.92x) for males and 0.86e\^(1.67x) for females). |
| Number of Participants with Statin-Associated Muscle Symptoms (SAMS) | Month 1, Month 2, and Month 3 | Number of participants reporting any muscle soreness, weakness, or stiffness as assessed by the SAMS questionnaire. |
| Change from Baseline in Body Weight (kg) | Baseline, Month 1, Month 2, Month 3 | Body weight measured in kilograms (kg) to evaluate changes during the training and intervention period. |
| Change from Baseline in Body Mass Index (kg/m^2) | Baseline, Month 1, Month 2, Month 3 | Body Mass Index (BMI) calculated as weight in kilograms divided by height in meters squared (kg/m\^2). |
Countries
Taiwan
Contacts
CONTACTYu-Hsuan Cheng, MD, MS
STUDY_CHAIRYu-Hsuan Cheng, MD, MS
Taipei Medical University
Outcome results
None listed