Distribution of creatine kinase in the general population: implications for statin therapy

Am Heart J. 2007 Oct;154(4):655-61. doi: 10.1016/j.ahj.2007.06.008.


Background: Eligible subjects with mildly elevated serum creatine kinase (CK) activity are often excluded before randomization in statin trials, but patients may potentially be misclassified as having hyperCKemia when inappropriate reference limits are used. Little information is usually given regarding how reference limit data were established, although evidence suggests that the variation of CK activity in the general population is wider than reflected in reference intervals in current use.

Methods: We determined reference intervals for serum CK according to National Committee on Clinical Laboratory Standards/Nordic Reference Interval Project guidelines, in a stratified random sample of the population, including 1444 individuals, aged 34 to 60 years, after 3 days of rest. Participants were mainly of white European (n = 503), South Asian (n = 292), or African descent (n = 580).

Results: The calculated upper reference limits (97.5th percentile) for nonblack and black women and men were 2 to 5 times higher than recommended by the assay manufacturer. Respectively 13% of the white Europeans, 23% of South Asians, and 49% of the black people had serum CK activities above the manufacturer-provided limits.

Conclusion: The variation in CK activity within the population is wider than previously suggested in smaller, nonrandom samples, and relatively high values occur frequently in all subgroups studied after rest. Therefore, we infer that upward adjustment of the upper reference limit is necessary for all population subgroups studied. The use of appropriately established reference intervals may improve the use of statins and particularly benefit the control of dyslipidemia in those with relatively high baseline CK activity.

MeSH terms

  • Adult
  • African Continental Ancestry Group / statistics & numerical data
  • Asian Continental Ancestry Group / statistics & numerical data
  • Creatine Kinase / blood*
  • European Continental Ancestry Group / statistics & numerical data
  • Female
  • Health Status
  • Humans
  • Male
  • Middle Aged
  • Netherlands / epidemiology
  • Reference Standards
  • Reference Values
  • Suriname / ethnology


  • Creatine Kinase