Elsevier

American Heart Journal

Volume 154, Issue 4, October 2007, Pages 655-661
American Heart Journal

Clinical Investigations
Prevention and Rehabilitation
Distribution of creatine kinase in the general population: Implications for statin therapy

https://doi.org/10.1016/j.ahj.2007.06.008Get rights and content

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.

Section snippets

Methods

Reference intervals were determined according to the guidelines of the Nordic Reference Interval Project and the Clinical Laboratory Standards Institute (CLSI, formerly the National Committee on Clinical Laboratory Standards [NCCLS]).13., 14.

Results

We obtained serum CK activities from 1444 citizens, aged 34 to 60 years, 503 of white European, 292 of South Asian, 580 of African, and 69 of other ancestry.

Discussion

To our knowledge, this is the first report on reference intervals for serum CK activity based on a random sample of the general population, including subjects of different ancestry, and standardizing for exercise. Our data suggest that relatively high CK activities commonly occur in the general population, including in people of European, South Asian, and African ancestry, and even after 3 days of rest.

The calculated upper reference limit in the total group as well as the limits in the

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