Brewster Lizzy M, Mairuhu Gideon, Sturk August, van Montfrans Gert A
Department of Internal and Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands.
Am Heart J. 2007 Oct;154(4):655-61. doi: 10.1016/j.ahj.2007.06.008.
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.
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).
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.
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.
在他汀类药物试验中，血清肌酸激酶（CK）活性轻度升高的合格受试者在随机分组前常被排除，但如果使用不恰当的参考限值，患者可能会被误诊为高CK血症。虽然有证据表明一般人群中CK活性的变异范围比目前使用的参考区间所反映的更宽，但关于参考限值数据是如何确定的信息通常很少给出。
我们根据美国国家临床实验室标准委员会/北欧参考区间项目指南，在一个分层随机抽样的人群中确定血清CK的参考区间，该人群包括1444名年龄在34至60岁之间、经过3天休息的个体。参与者主要为欧洲白人（n = 503）、南亚人（n = 292）或非洲裔（n = 580）。
计算得出的非黑人与黑人女性及男性CK活性的上参考限值（第97.5百分位数）比检测试剂盒制造商推荐的值高2至5倍。分别有13%的欧洲白人、23%的南亚人和49%的黑人血清CK活性高于制造商提供的限值。
人群中CK活性的变异范围比之前在较小的非随机样本中所显示的更宽，并且在所有研究的亚组中，休息后CK活性相对较高的值经常出现。因此，我们推断对于所有研究的人群亚组，都有必要上调上参考限值。使用适当确定的参考区间可能会改善他汀类药物的使用，尤其有益于控制基线CK活性相对较高者的血脂异常。
