Elsevier

Clinica Chimica Acta

Volume 279, Issues 1–2, 1 January 1999, Pages 107-115
Clinica Chimica Acta

Distribution of serum creatine kinase activity in young healthy persons

https://doi.org/10.1016/S0009-8981(98)00180-6Get rights and content

Abstract

The normal distribution of serum creatine kinase (CK) was determined in 428 men (mean age=21.5) and 540 women (mean age=20.2). The bootstrap method was employed to obtain statistical parameters of CK reference range and correlations with physical activity habits, BMI, cigarette smoking and alcohol consumption. CK distribution was non-Gaussian and skewed toward the higher values; 18.9% of the men and 4.6% of the women had values above the upper reference limits defined for the commercial assay kit. The median 97.5 percentile value was 532 u/l for men and 248 u/l for women (95% confidence interval of 384–738 u/l and 184–340 u/l, respectively). A significant correlation was found only between CK and alcohol consumption in men. Myoglobin level in a representative group of subjects correlated well with CK activity for both genders. Our findings define the range of CK values in a healthy, young, heterogeneous population. We suggest that only CK levels above the determined 97.5 percentile should warrant further clinical investigation.

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.

Section snippets

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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