Pairs of Creatine Kinase Serum Activity

Dirk Moßhammer*, 1, Rainer Muche2, Dagmar Menzel3, Christina Ring2, Dorothee Wernet3, Christoph Meisner4, Christoph H. Gleiter5, Gernot Lorenz1, Klaus Mörike5
1 Division of General Medicine, University of Tübingen
2 Institute of Biometrics, University of Ulm
3 Institute for Clini-cal and Experimental Transfusion Medicine, University Hospital of Tübingen
4 Institute of Medical Biometrics, Univer-sity Hospital of Tübingen and
5 Institute of Pharmacology and Toxicology, Department of Clinical Pharmacology, Uni-versity Hospital of Tübingen

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© 2009 Moßhammer et al;

open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

* Address correspondence to this author at the Division of General Medi-cine, University Tübingen, Keplerstrasse 15, D-72074 Tübingen, Germany; Tel: +49 7071 29 80255; Fax: +49 7071 29 5896; E-mail:


Background: For patients with an increased risk of developing myopathy with statin treatment, guidelines recommend to measure CK before and 6-12 weeks after initiating statin treatment. Further, in clinical trials of statins, the number of patients experiencing elevated creatine kinase (CK) serum activity is commonly reported as a safety parameter. Usually exceeding the upper limit of normal (ULN) is used as the basis of description to characterize muscular damage potentially caused by statins. Therefore, basic data on both, proportions of patients with specific CK increases, and absolute and relative CK increases, would be helpful to assess potential CK chances in patients. However, no such data are available so far.

Methods: CK activity was measured in a group of blood donors (n=40) at two occasions 10 weeks apart. The 95th percentile of absolute and relative CK increases was selected to separate true from irrelevant changes. A CK difference was defined to be true if a random measurement error of 10% was exceeded. The numbers of subjects with true CK differences were characterised by both measurements being under, crossing, or being above ULN, and twice ULN, respectively. Results: Five percent of subjects (95th percentile) had an increase of CK more than 139% (men) or 120% (women), respectively, as compared with the first measurement. Five percent of subjects had an absolute difference of at least 94 U/l (men) and 16 U/l (women), respectively. Thirty-one percent of subjects had both CK activities below 2 times the ULN. Six percent of them had the first measurement under and the second above ULN. In three percent, the first measurement was under and the second above 2 times the ULN. In no subject, the first and the second measurement was above 2 times the ULN.

Conclusion: It is concluded that CK serum activity substantially varies between two measurements. The present data provide the basis for developing reference ranges of CK activity pairs by simple variables that can be useful for practitioners and trialists.

Keywords: Lipid-lowering therapy, myopathy, statins, creatine kinase.