Exercise-induced Muscle Damage in Statin Users

Study Overview
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Brief Summary
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Rationale: Combining statin treatment and physical activity is very effective for the prevention of cardiovascular diseases. Statins are well-tolerated by most patients, but may cause statin-associated muscle symptoms (SAMS) and elevated markers of skeletal muscle damage in some patients. Several studies have shown that statins augment increases in serum creatine kinase after eccentric or vigorous exercise. If statins also increase muscle damage markers after exercises of moderate intensity is unclear. Symptomatic statin users may be more susceptible to exercise-induced skeletal muscle injury, however, previous studies did not differentiate between symptomatic and asymptomatic statin users. Objective: To compare the impact of moderate-intensity exercise on muscle damage markers between symptomatic and asymptomatic statin users, and non-statin using controls. A secondary objective is to examine the association between leukocytes coenzyme Q10 levels and exercise-induced muscle damage and muscle complaints.

Detailed Description
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Combining statin treatment and physical activity is very effective for the prevention of cardiovascular diseases. Statins are well-tolerated by most patients, but may cause statin-associated muscle symptoms (SAMS) and elevated markers of skeletal muscle damage in some patients. Several studies have shown that statins augment increases in serum creatine kinase after eccentric or vigorous exercise. However. if statins also increase muscle damage markers after exercises of moderate intensity is unclear. Impaired mitochondrial oxidative function might contribute to SAMS and exercise-induced muscle damage. Several studies showed that statins decrease serum coenzyme Q10 levels, an essential component of the mitochondrial transport chain, but effects on intramuscular coenzyme Q10 levels are inconsistent. The investigators have observed that mitochondrial dysfunction is more pronounced in statin users with SAMS compared to asymptomatic statin users. This suggests that symptomatic statin users may be more susceptible to exercise-induced skeletal muscle injury. However, previous studies examining creatine kinase response to exercise did not differentiate between symptomatic and asymptomatic statin users. In this cross-sectional observational study the investigators will study the impact of moderate-intensity exercise on muscle damage markers between symptomatic and asymptomatic statin users, and non-statin using controls. A secondary objective is to examine the association between leukocytes coenzyme Q10 levels and exercise-induced muscle damage and muscle complaints. The investigators hypothesize that statins will not increase muscle damage markers after moderate-intensity exercise and that higher CoQ10 levels are associated with less exercise-induced muscle damage and muscle complaints.

Official Title
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The Effects of Statins on Muscle Damage Markers After Moderate-intensity Exercise

Conditions
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Cardiovascular Diseases, HMG COA Reductase Inhibitor Adverse Reaction, Muscle Damage

Intervention / Treatment
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* Other: Moderate-intensity exercise


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Mentally able to give informed consent Statin groups: statin treatment for at least 3 months Exclusion Criteria: Known hereditary muscle defect Known mitochondrial disease Diabetes Mellitus Hypo- or hyperthyroidism Other diseases known to cause muscle symptoms (e.g. m. Parkinson or rheumatic diseases) Coenzyme Q10 supplementation

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 75 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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Symptomatic statin users<br>Statin users with self-reported muscle symptoms | Other: Moderate-intensity exercise<br>* Participants will walk either 30km, 40km or 50km for four consecutive days during the Nijmegen Four Days Marches. Measurements will be performed after the finish of the first, second and third walking day.<br>|
| Asymptomatic statin users<br>Statin users without muscle symptoms | Other: Moderate-intensity exercise<br>* Participants will walk either 30km, 40km or 50km for four consecutive days during the Nijmegen Four Days Marches. Measurements will be performed after the finish of the first, second and third walking day.<br>|
| Non-statin using controls<br>Participants not using statins | Other: Moderate-intensity exercise<br>* Participants will walk either 30km, 40km or 50km for four consecutive days during the Nijmegen Four Days Marches. Measurements will be performed after the finish of the first, second and third walking day.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Muscle damage markers | Change in muscle damage markers (creatine kinase, myoglobin, lactate dehydrogenase, troponin I and BNP) from baseline to post-exercise | Baseline (before exercise) and after three days of moderate-intensity walking exercise (measured each day) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Muscle pain scores | Muscle pain scores measured with the Brief Pain Inventory questionnaire (10 point scale with 0 representing no pain and 10 the worst pain imaginable) | Baseline (before exercise) and after three days of moderate-intensity walking exercise (measured each day) | 
| Muscle strength and fatigue | M. Quadriceps muscle strength and fatigue measured using electrical stimulation | Baseline (before exercise) and after one day of moderate-intensity walking exercise | 
| Coenzyme Q10 levels | Coenzyme Q10 levels measured in leukocytes | At baseline | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Statin-associated muscle symptoms, Muscle damage markers, Moderate-intensity exercise, Coenzyme Q10