Distribution of serum creatine kinase activity in young healthy persons
Introduction
Serum total creatine kinase (EC2.7.3..2; CK) activity is still routinely used as a marker in the diagnosis of muscle disorders and in the evaluation of acute chest pain. However, the interpretation of an elevated CK value is often difficult because the enzyme activity may be increased in many neuromuscular diseases, after intramuscular injections or vigorous physical activity and without an apparent cause-idiopathic hyperCKemia 1, 2, 3, 4, 5, 6.
One of the major problems in defining CK abnormality is the determination of the normal reference range. Gender, race, age and possibly muscle mass were reported to affect CK activity 7, 8, 9, 10, 11. In addition, it has been shown that the distribution of CK values in a healthy population is markedly skewed toward the higher values and remains non-Gaussian, even after logarithmic transformation of the data 7, 12, 13. Despite this fact, most laboratories rely on the central 95% of observations for reference range determination 7, 12, 14, 15, although this method assumes normal distribution and has limited accuracy for highly skewed parameters. In addition, a reliable estimate of the upper 97.5th percentile of CK values, requires a large data base, at least 400 subjects, according to the recommendations of Miller et al. [12]. However, most previous studies included smaller sample groups. Furthermore, most of these studies examined a wide range of ages and did not test a representative cross section of the population, as they tested mainly patients 8, 15, hospital employees 7, 10or volunteers involved in other genetic studies [12].
Because of these shortcomings and clinical experience showing many young adults with `elevated' CK levels, we conducted a study to determine the distribution of serum CK activity in the young healthy population in Israel. We focused on a limited age group (20–25 years) and analyzed men and women separately, with each group comprising of more than 400 subjects. Since standard statistical methods are less accurate in such applications, we employed the bootstrap method [16]to evaluate CK distribution and the 97.5 percentile. Correlations between CK values to factors such as ethnic origin, body mass index (BMI), physical activity habits and markers of muscle breakdown, were sought.
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Subjects
Israeli army service personnel were randomly examined on the day of discharge. The examination included blood withdrawal, height and weight measurement and completion of a standard questionnaire. This was part of a more extended project for evaluating the health status of young persons in Israel, conducted by the Medical Corps. All subjects gave informed consent for testing and no conditions for participation were imposed. Nearly all of them arrived for discharge and testing after a few weeks
Results
The distribution of CK activities in our young healthy population was non-Gaussian, with marked skewness toward the higher values, both for men and for women (Fig. 1). This was not corrected when plotted on a logarithmic scale. Men had mean CK values of 162.9 u/l (median of 124 u/l and range of 14–1525 u/l), while women had mean values of 89.1 u/l (median of 75 u/l and range of 12–1233 u/l). In addition, 18.9% of the men and 4.6% of the women had values above the upper reference limits defined
Discussion
Normal ranges of CK values were determined by evaluating CK levels in a randomly selected heterogeneous population of young healthy adults. We considered that these values would provide less contaminated baselines than other reports which included patients, hospital employees or volunteers involved in other studies 7, 8, 10, 12, 15.
The previously observed skewed distribution of serum CK, uncorrected by logarithmic transformation 7, 12, 13was also observed in our group. As in previous studies
Acknowledgements
We wish to thank Yona Zaide Msc. and Sergio Cuznir B.A. of the Medical Corps Laboratory for their excellent technical work. We are also grateful to Prof. A. Gutman and Prof M. Mayer of the Hadassah Clinical Biochemistry Department for their comments and suggestions on the work and manuscript.
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2009, Journal of Science and Medicine in SportCitation Excerpt :The upper limits of the 97.5th and 90th percentiles for plasma CK activity were 1.338 U/L and 975 U/L, respectively, which are markedly higher than the level of 398 U/L recently reported for non-athletes by Stromme et al. [19] These marked discrepancies are most likely related to the bouts of intense exercise experienced by the soccer players daily, which causes a significant amount of skeletal muscle stress and may lead to the elevated plasma CK values. In agreement with this interpretation, Lev et al. [20] reported that the mean plasma CK measurements of 428 male soldiers from the Israeli Army at different moments were around 544 U/L. In addition, Thompson et al. [21] showed that individuals doing uninterrupted exercise (90 min hard effort interspersed with walking) had peaks of plasma CK activity with a mean value of 774 U/L.
Distribution of creatine kinase in the general population: Implications for statin therapy
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