Exercise-induced Muscle Damage in Statin Users

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

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.

Study Overview

• Status: Completed
• Conditions: Cardiovascular Diseases; Muscle Damage; HMG COA Reductase Inhibitor Adverse Reaction
• Intervention / Treatment: Other: Moderate-intensity exercise

Detailed Description

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.

• Study Type: Observational
• Enrollment (Actual): 100

Contacts and Locations

Study Locations

• Netherlands
  • Nijmegen, Netherlands, 6525 EX
    • Department of Physiology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Symptomatic statin users (n=35), asymptomatic statin users (n=34) and non-statin using controls (n=31).

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Symptomatic statin users; Statin users with self-reported muscle symptoms	Other: Moderate-intensity exercise; 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.
Asymptomatic statin users; Statin users without muscle symptoms	Other: Moderate-intensity exercise; 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.
Non-statin using controls; Participants not using statins	Other: Moderate-intensity exercise; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Radboud University Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): May 29, 2018
• Primary Completion (Actual): July 20, 2018
• Study Completion (Actual): July 20, 2018

Study Registration Dates

• First Submitted: August 15, 2021
• First Submitted That Met QC Criteria: August 15, 2021
• First Posted (Actual): August 18, 2021

Study Record Updates

• Last Update Posted (Actual): August 27, 2021
• Last Update Submitted That Met QC Criteria: August 23, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Keywords: Coenzyme Q10; Statin-associated muscle symptoms; Muscle damage markers; Moderate-intensity exercise
• Additional Relevant MeSH Terms: Cardiovascular Diseases
• Other Study ID Numbers: CMO 2007-148

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No