Variation of serum creatine kinase (CK) levels and prevalence of persistent hyperCKemia in a Norwegian normal population. The Tromsø Study

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Abstract

In this cross-sectional study we assessed the prevalence of hyperCKemia, defined as persistent CK values ⩾210 U/L in women, ⩾400 U/L in men <50 years and ⩾280 U/L in men ⩾50 years (reference values according to the Nordic Reference Interval Project).

Blood samples were obtained from 12,828 participants in the 6th survey of The Tromsø Study. We identified 686 (5.3%) individuals with incidentally elevated CK. After a standardized control test, 169 persons (1.3%) had persistent hyperCKemia, i.e. 69.9% normalization. Use of statins or other causes of hyperCKemia were detected in 78 individuals (46.2%), giving a prevalence of “idiopathic hyperCKemia” of 0.71%. CK variation was highest in younger men and in females between 60 and 69 years. This study has identified persistent hyperCKemia in 1.3% of the normal population, and demonstrates the importance of performing controlled CK analyses, also in those with identified risk factors.

Introduction

Increased serum creatine kinase level (hyperCKemia) is an important marker of neuromuscular diseases, but may increase in a number of other diseases such as cardiac diseases, malignancies, systemic metabolic disorders, thyroid, parathyroid and haematologic diseases [1], [2]. Alcohol and drug abuse, medications like statins and beta-blockers, and physical activity are also related to hyperCKemia and therefore make the test less specific [3], [4], [5], [6]. Despite numerous reported causes of increased CK, a group of individuals with “idiopathic” hyperCKemia has been subject to investigation [7], [8], [9]. In a retrospective evaluation of 114 selected asymptomatic or oligosymptomatic individuals with incidentally detected persistent hyperCKemia, a definite neuromuscular diagnosis was found in 18% [10].

In the follow up study 6 years later, which included 55 of the 93 undiagnosed individuals, 43 subjects (80%) had idiopathic hyperCKemia [11]. Most of them remained asymptomatic and had not developed specific neuromuscular diseases.

Previous reports focusing on causes of hyperCKemia are mainly based on selected patients referred to specialized centers, or retrospective groups of patients. Small samples and lack of standardized criteria for identification of groups at risk of underlying neuromuscular disorders makes it difficult to extrapolate these results to the general population [10], [12], [13].

CK levels vary in different ethnicities; black men and South Asians usually have higher CK values at rest than Caucasians [5], [14]. Recent data indicate that the variation in CK values in normal populations are wider than reflected in hospital reference intervals, which may have clinical implications [14]. Information about the prevalence of marked elevated CK (>5000 U/L) in unselected, normal, populations is limited. Knowledge about CK-distribution and prevalence of persistent hyperCKemia in the general population may therefore be informative for both clinical and scientific purposes. In patients with hyperCKemia, it is also important for the clinician to know how CK varies with different physiologic conditions.

The purpose of this study was to investigate the age- and gender-specific prevalence of persisting hyperCKemia in a Norwegian, almost pure Caucasian population, and to study the variation of CK and the frequency of normalization after a standardized control test. We also assessed possible causes of hyperCKemia based on self-reported information from questionnaires.

Section snippets

Recruitment of participants

All participants were recruited from the 6th survey of The Tromsø Study from October 2007 to December 2008 [15]. The Tromsø Study is a single-center, population-based prospective study with repeated health surveys since 1974 of inhabitants in the municipality of Tromsø, Norway. A total of 10,137 women and 9625 men aged 30–87 years were invited (Fig. 1). They were recruited from 4 different groups; (1) all participants from phase 2 of the 4th survey (1994–1995), (2) a 10% random sample of persons

Results

CK was measured in 6834 women and 5994 men aged 30–87 years (mean 58 years) giving an overall response rate of 65% (Fig. 1). In men, the response rate was 63%, highest in the age group 60–69 years (73%) and lowest among the youngest and the elderly (Table 1). In women, the response rate was 67% with highest attendance between 60 and 69 years (79%) and lowest in the age groups 30–39 and 80+ (Table 1). Mean age of the 35% non-responders was 56 years. Median CK value in the total population was 84 U/L

Discussion

In this population-based study persistent hyperCKemia was found in 1.3% of men and women. Almost 70% with incidentally detected hyperCKemia normalized in subsequent control samples. A possible cause of persistent hyperCKemia was found in 46.2% of the individuals, where statin use comprised nearly half. In statin users, the proportion of persistent hyperCKemia was higher in women than in men, and the CK-level in women on statins was significantly higher than in hyperCKemic women not using this

Acknowledgements

We wish to thank Mrs. Anna-Kirsti Kvitnes and Mrs. Irene Lund at the National Neuromuscular Centre, University Hospital North Norway, for practical and technical support with the study.

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