Effect of Statins on Creatine Kinase Levels Before and After a Marathon Run

doi:10.1016/j.amjcard.2011.08.045

The American Journal of Cardiology

Volume 109, Issue 2, 15 January 2012, Pages 282-287

https://doi.org/10.1016/j.amjcard.2011.08.045 Get rights and content

We measured the serum levels of myoglobin, total creatine kinase (CK), and the CK myocardial (CK-MB), muscle (CK-MM), and brain (CK-BB) isoenzymes in 37 subjects treated with statins and 43 nonstatin-treated controls running the 2011 Boston Marathon. Venous blood samples were obtained the day before (PRE) and within 1 hour (FINISH) and 24 hours after (POST) the race. The hematocrit and hemoglobin values were used to adjust for changes in the plasma volume. The CK distribution was normalized using log transformation before analysis. The exercise-related increase in CK 24 hours after exercise, adjusted for changes in plasma volume, was greater in the statin users (PRE to POST 133 ± 15 to 1,104 ± 150 U/L) than in the controls (PRE to POST 125 ± 12 to 813 ± 137 U/L; p = 0.03 for comparison). The increase in CK-MB 24 hours after exercise was also greater in the statin users (PRE to POST 1.1 ± 3.9 to 8.9 ± 7.0 U/L) than in the controls (PRE to POST 0.0 ± 0.0 to 4.2 ± 5.0 U/L; p <0.05 for comparison). However, the increases in muscle myoglobin did not differ at any point between the 2 groups. Increases in CK at both FINISH and POST race measurements were directly related to age in the statin users (r² = 0.13 and r² = 0.14, respectively; p <0.05) but not in the controls (r² = 0.02 and r² = 0.00, respectively; p >0.42), suggesting that susceptibility to exercise-induced muscle injury with statins increases with age. In conclusion, our results show that statins increase exercise-related muscle injury.

Section snippets

Methods

A total of 37 statin-using athletes (29 men and 8 women) and 43 controls (30 men and 13 women) were recruited through an e-mail sent to all participants registered for the 115th Boston Athletic Association Marathon held on April 18, 2011. The subjects were recruited if they had either continuously received statin therapy for >6 months or not used any lipid-lowering medication. Subjects were nonsmokers, aged ≥35 years, and free of known cardiovascular or metabolic disease, except

Results

The statin and control group subjects were of similar training status and health (Table 1). The control subjects performed more hours of moderate physical activity than did the statin subjects the day after the marathon (3.8 ± 2.4 vs 2.2 ± 1.7 hours; p <0.01), but the other self-reported categories of physical activity did not differ between the groups or before and after the marathon (all p >0.10). The statin users were treated with a variety of statins and statin doses (Table 2). The average

Discussion

Marathon running is associated with marked muscle damage. The CK levels are on average 2 to 5 times greater than baseline immediately after completion of a marathon3, 13 and 13- to 15-fold greater at 24 hours after the race. Considerable interindividual variation exists in the CK response, with individual values ranging from <1,000 to >9,000 U/L.¹⁴ This variability in the CK response is partly attributable to factors affecting performance such as fitness and training. For example, the CK

Acknowledgments

The research assistants were Charles d'Hemecourt, BS, Lindsay Lorson, BS, and William Roman, BS; logistical support was provided by Dave McGillivray, BS, the Boston Athletic Association, Boston, Massachusetts, and Quest Diagnostics, Madison, New Jersey.

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Statin use may exacerbate exercise-induced skeletal muscle injury caused by reduced coenzyme Q10 (CoQ10) levels, which are postulated to produce mitochondrial dysfunction.
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Lipid-lowering management of patients affected by mitochondrial myopathy is quite challenging. Although statins are not contraindicated in patients with inherited myopathies, they have to be used with caution, being potentially able to cause toxic effects on skeletal muscle through a disturbance of mitochondrial function7 and exacerbate exercise-induced skeletal muscle injury also in healthy patients.8,9 In our specific case, the mild inflammatory pattern observed in the muscle biopsy could be a residue of a statin-related myositis.
A 48-year-old man presented to our lipid clinic with statin intolerance and elevated serum creatine kinase levels, being affected by mitochondrial myopathy because of heteroplasmic mitochondrial DNA missense mutation in MTCO1 gene (m.7671T>A). He had just been treated with a coronary artery bypass 4 years before because of acute coronary syndrome, and he had consistently high levels of both low-density lipoprotein cholesterol and triglycerides. Dyslipidemia was successfully treated using 75 mg of alirocumab subcutaneously every 2 weeks, 10 mg of ezetimibe daily, 2 g of marine omega-3 fatty acids daily, and 145 mg of micronized fenofibrate every 2 days. Although muscle weakness persisted, myalgia did not reoccur and serum creatine kinase levels remained almost stable over the time.
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At the end of the study, 9 athletes did not take any drug, 1 was on lovastatin, 1 on cholestyramine, 5 on atorvastatin and 6 on fenofibrate [41]. With regard to marathon runners, Parker et al. [34] found that statin users (n = 37) had a significantly greater increase in CK levels measured 24 h after the 2011 Boston marathon compared with statin non-users (n = 43); serum myoglobin did not differ between the 2 studied groups. Furthermore, a direct correlation was reported between elevations in CK and increasing age in statin users (but not in controls), thus highlighting that age may increase the susceptibility to statin-related muscle injury after exercise [34].
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: This study was funded by a research grant from Hartford Hospital (Hartford, Connecticut).

: Dr. Thompson is a consultant for AstraZenica International, Wilmington, Delaware, Merck & Co., Inc., Whitehouse Station, New Jersey, the Schering-Plough Corporation, Kenilworth, New Jersey, Takeda Pharmaceutical Company, Limited, Deerfield, Illinois, Roche, Inc., Indianapolis, Indiana, and Genomas, Inc., Hartford, Connecticut and is a member of the speaker's bureau for Merck & Co., Inc., Whitehouse Station, New Jersey, Pfizer, Inc., Groton, Connecticut, Abbott Laboratories, Abbott Park, Illinois, AstraZenica International, Wilmington, Delaware, and the Schering-Plough Corporation, Kenilworth, New Jersey.

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MiscellaneousEffect of Statins on Creatine Kinase Levels Before and After a Marathon Run

Section snippets

Methods

Results

Discussion

Acknowledgments

Am J Cardiol

Metabolism

Am J Cardiol

J Am Coll Cardiol

Metabolism

Clin Chim Acta

Kidney Int

USA marathoning: 2009 overview

Effect of marathon running on hematologic and biochemical laboratory parameters, including cardiac markers

Am J Clin Pathol

Statin-associated myopathy

JAMA

Metabolic changes following eccentric exercise in trained and untrained men

J Appl Physiol

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

Clin Chem

Physical activity and incidence of hypertension in college alumni

Am J Epidemiol

Evaluation of hemoconcentration from hematocrit measurements

J Appl Physiol

Switching statin therapy using a pharmacist-managed therapeutic conversion program versus usual care conversion among indigent patients

Pharmacotherapy

Miscellaneous
Effect of Statins on Creatine Kinase Levels Before and After a Marathon Run