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.

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.