The creatine kinase response to eccentric exercise with atorvastatin 10 mg or 80 mg

doi:10.1016/j.atherosclerosis.2007.12.029

Atherosclerosis

Volume 200, Issue 1, September 2008, Pages 121-125

https://doi.org/10.1016/j.atherosclerosis.2007.12.029 Get rights and content

Abstract

Introduction

Methods

79 subjects with LDL cholesterol > 100 mg/dL were randomly assigned to atorvastatin 10 mg (N = 42) or 80 mg (N = 37) for 5 weeks. Subjects performed a downhill walking exercise during the fifth week of treatment. Leg muscle soreness, plasma CK and CK-MB levels were measured daily for 4 days following the exercise.

Results

CK, CK-MB and muscle soreness increased above pre-exercise levels in all subjects after the exercise. There were no differences in the CK, CK-MB or soreness response between the high and low dose treatment groups at any time point.

Conclusion

The downhill walking model of muscle injury does not distinguish between high and low dose atorvastatin therapy either because this test is insensitive to differences among statin doses or because there is no difference in muscle injury between these two drug doses with this statin. Clinicians should be aware, however, that exercise can increase CK levels with even low dose statin therapy.

Introduction

Hydroxy-methyl-glutaryl co-enzyme A (HMG-CoA) reductase inhibitors or statins are well tolerated by most patients, but can produce a variety of skeletal muscle problems including mylagia, creatine kinase (CK) elevations and clinically important rhabdomyolysis. Few studies have compared different statins or even different doses of statins for their myopathic potential. We have previously demonstrated that statins increase CK blood levels after downhill walking [1]. Downhill walking is an eccentrically based exercise, a physical task in which the muscle is forced to contract while simultaneously being stretched, and is known to injure skeletal muscle and to increase CK levels. The present study was designed to determine if the CK response to downhill walking differed between two doses of atorvastatin. The ultimate goal of this and additional studies was to determine if eccentric exercise could be used to compare the myopathic potential of different does of statins and ultimately to compare the myopathic effect of different cholesterol lowering medications. The hypotheses of this study were that atorvastatin 80 mg would cause greater exercise-induced increases in plasma CK levels and CK-MB than atorvastatin 10 mg.

Section snippets

Subjects and study design

Participants were men who exercised less than once per week during the preceding 6 months, consumed on average fewer than two alcoholic beverages per day, and were free of any chronic medical conditions requiring medication. Subjects provided written informed consent as approved by the institutional review boards at Hartford Hospital and the University of Massachusetts, Amherst. Women were not recruited because they appear relatively protected from exercise-induced CK release compared to men [2]

Laboratory analysis

Blood was obtained via venipuncture from a prominent forearm vein and collected into a 3 ml sterile or heparinized vacutainer (BD Vacutainer, Franklin Lakes, NJ). Blood lipids, CK and CK-MB analyses were performed at the Hartford Hospital Clinical Laboratory. Samples obtained at the University of Massachusetts were shipped on dry ice to the central laboratory for analysis.

Total cholesterol (Roche Cobas #03039773, Indianapolis, IN), high-density lipoprotein cholesterol (HDL-C) (Roche Cobas

Results

Of the 87 subjects randomized to atorvastatin (10 mg or 80 mg), 79 completed the study protocol. Eight subjects discontinued the study due to time conflicts, protocol violation, or unrelated medical issues (4 randomized to 80 mg, 4 randomized to 10 mg). Thus, 42 subjects were in the atorvastatin 10 mg group and 37 in the atorvastatin 80 mg group. Baseline age, height, weight and body mass index (BMI) were similar between the two groups (Table 1).

Discussion

We have previously documented greater CK increases after downhill walking exercise in statin versus placebo treated subjects [1]. The present study compared the exercise CK response to two different doses of the most frequently used statin, atorvastatin. The goal was to determine if the eccentric exercise CK response could be used to compare the myopathic potential of different statin doses and ultimately to compare the exercise CK response to different drug combinations and to new medications.

Acknowledgements

This study was funded by an investigator initiated grant from Merck Pharmaceuticals. The authors would like to thank Karen Riska M.S. and Sachin Shah, Pharm.D for their significant contributions to the study.

Paul D. Thompson acknowledges: research support from Merck, Pfizer, and Astra Zenica; speaking honoraria from Merck, Pfizer, KOS Pharmaceuticals, Astra Zenica, Schering–Plough, Reliant Pharmaceuticals and Abbott Laboratories; stock ownership in Schering Plough, Pfizer and Merck.

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Eight of the 16 studies were RCTs, 2 of which were not placebo controlled. Nine6,7,19,20,40–42,37,38 of these 17 trials found an association between statin use and exercise with myalgia. As a consequence, 47% of the studies examining whether statins exacerbated myalgia during exercise demonstrated an increase in adverse muscle symptoms.
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Statin therapy reduces atherosclerotic cardiovascular disease (CVD) events. Regular physical activity is also associated with reduced CVD events, but statin therapy can produce muscle complaints, which may be more frequent in physically active individuals. We reviewed the literature to determine the effects of statins on symptoms, exercise performance and activity levels in physically active individuals.
We performed a PubMed search to identify English language articles reporting on statins and their effect on athletic/exercise performance, and symptoms in active individuals.
We identified 65 articles, 32 of which provided sufficient information to be included in this review. Seventeen of the 32 studies examined the incidence of myalgia while exercising on statins, and showed that myalgia was increased in 8 of the 17 (47%) of these studies. Of the 17 studies examining the effects of statin therapy on muscle injury, 6 (35%) studies reported that statins augment the increase in creatine kinase (CK) produced by exercise. There were 10 studies that examined statin effects on aerobic exercise performance, only 3 of which (33%) concluded that statins decreased performance. Two (25%) of the 8 studies examined the effects of statins on muscular strength and suggested that statins decreased muscular strength, whereas 2 (25%) reported increased strength. Statins did not consistently affect physical activity levels since statins were associated with an increase in activity in 3 of the 5 studies examining habitual exercise. None of the studies showed a relationship between statins use and exercise and an increase in myalgia or a decrease in exercise performance. There was also no correlation between intensity of statin therapy and an effect on these variables.
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The creatine kinase response to eccentric exercise with atorvastatin 10 mg or 80 mg

Abstract

Introduction

Methods

Results

Conclusion

Introduction

Section snippets

Subjects and study design

Laboratory analysis

Results

Discussion

Acknowledgements

Metabolism

Am J Cardiol

Metabolism

Influence of estrogen on markers of muscle tissue damage following eccentric exercise

Fiziol Cheloveka

Time course of muscle adaptation after high force eccentric exercise

Eur J Appl Physiol Occup Physiol

Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge

Clin Chem

Lovastatin use and muscle damage in healthy volunteers undergoing eccentric muscle exercise

West J Med