Elevated creatine kinase (CK) is very common in clinical patients, and cardiology is often called for consultation. Combined with 2 recent cases with significant and continuous increase in CK, summarize and analyze the reasons for the increase in CK: Case 1Female, 80 years old, with a history of coronary heart disease and hyperlipidemia, long-term oral statin therapy, no abnormality in annual physical examination . The patient’s physical examination 1 month ago showed biochemical findings: CK 550 U/L (normal reference range: 50-310 U/L), CK-MB, and liver and kidney functions were normal. The patient reported no symptoms such as muscle pain, fatigue, chest pain, and chest tightness. Complete ECG and echocardiography were normal. The muscle damage caused by statin was considered first, and statin was stopped immediately. After 2 weeks of drug withdrawal, CK continued to increase significantly, fluctuating between 1000 and 2000 U/L. The patient still had no symptoms such as chest pain, chest tightness, myalgia, and muscle weakness. Case 2Male, 67 years old. Past history of coronary heart disease, hypertension, and hyperthyroidism. 15 years ago underwent PCI treatment, implanted a stent in the anterior descending artery (specifically unknown), and received long-term oral aspirin antiplatelet and statin therapy (atorvastatin 20 mg 1/night). The symptoms of lower extremity weakness appeared 3 months ago, which worsened after exercise. There was no chest pain, chest tightness, myalgia and other symptoms, and the muscle strength of both lower extremities was normal. Biochemical prompts: CK 250 U/L (normal reference range: 24-194 U/L), CK-MB and liver and kidney function were normal, which did not attract attention. 1 month ago, the patient’s above-mentioned fatigue symptoms worsened, and the biochemical examination showed that CK 566 U/L, CK-MB, and liver and kidney function were normal. Atorvastatin medication was discontinued, and the patient was instructed to avoid strenuous exercise. The above symptoms of fatigue were relieved, and the biochemistry was re-examined: CK 1174 U/L, CK-MB 56 U/L (reference value: 0-25 U/L), and liver, kidney and thyroid functions were normal. The patient has no history of taking traditional Chinese medicine and other special drugs, strenuous exercise or extrusion. （▲▼ Scroll up and down to view all content）These two cases have certain similarities, both of which have increased CK after taking statin and discontinued the drug< It continued to increase after span>. Patients have mild symptoms or no obvious symptoms. We analyze the above 2 cases:• First, what causes the increase in CK? Do statins cause muscle damage? Or is the muscle itself diseased? Or is it muscle damage caused by other diseases? • Second, what checks should be improved next? How often to review CK? • Finally, what should be done? Refer to relevant literature. In 2010, the European Federation of Neurological Societies (EFNS) issued an operational guideline on the “diagnostic method of mildly symptomatic/asymptomatic hyperCKemia”. 
2016 Journal of Neurology and Neurorehabilitation published the guideline for one year Interpretation of “Guidelines for the Diagnosis of Mild/Asymptomatic Hypercreatine Kinaseemia and Recent Developments”. 
Combining these two papers, learn the related content of hypocreatine kinase hyperemia.
1. Creatine Kinase (CK) Overview p>
• Creatine kinase (CK) is an 86 kD dimeric enzyme that catalyzes creatine and adenosine triphosphate The reaction forms creatine phosphate and adenosine diphosphate, a reaction that is critical for cellular energy production and metabolism.
• CK consists of 3 subtypes: CK-MM (mainly present in skeletal muscle), CK-MB (in the heart muscle) and CK-BB (in the brain).
• The serum CK test value is the sum of the three subtypes.
• Elevated serum CK levels are a common clinical phenomenon. Decomposition detection, can roughly determine the cause of the increase in serum CK.
• In actual clinical work, the elevation of serum CK-MB level caused by myocardial damage is the most common. Followed by increased serum CK-BB levels due to massive stroke, whereasElevated serum CK-MM levels associated with neuromyopathy are relatively uncommon.
2. The normal value of CK and the critical point to initiate screening
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There were significant racial and gender differences in serum CK values, among which the African population was higher than the Caucasian, and the male was higher than the female.
The guidelines recommend the use of Dutch study data as the upper limit of normal (ULN) for serum CK Basic data: 217 U/L for non-Black women, 336 U/L for non-Black men, 414 U/L for Black women, and 801 U/L for Black men.
In actual clinical work, clinicians often ignore laboratory test results that are slightly higher than ULN. In general, there is no adverse clinical outcome. Guidelines recommend setting the cutoff point to initiate screening for muscle disease at 1.5 times the upper limit of normal (ULN) for serum CK.
3. Mildly symptomatic hyperCKemia and asymptomatic hyperCKemia
mildly symptomatic hyperCKemia: to exclude non-myopathic hyperCKemia, Absence of any objective signs of muscle disease (eg, muscle weakness, atrophy, hypertrophy, or rigidity), but the presence of nonspecific, mild neuromuscular symptoms (eg, myalgia, excessive fatigue, exercise intolerance, spasticity, and stiffness) of hyperCKemia. Asymptomatic hyperCKemia: To exclude non-myopathic hyperCKemia, hyperCKemia without any neuromuscular symptoms or signs. Definition is a bit tricky, under our analysis, mild symptoms/asymptomatic hyperCKemia = exclusion of non-myopathy + no objective muscle disease/signs + mild, nonspecific symptoms or asymptomatic + hyperCKemia disease. That is, the definition of mild/asymptomatic hyperCKemia first excludes non-myopathic hyperCKemia. In other words, patients with mild/asymptomatic hyperCKemia have myopathic causes of increased CK.
Therefore, hyperCKemia can be firstly divided into myogenicand Non-myogenic.
Non-myopathic hyperCKemia refers to serum CK levels caused by other causes other than muscle disease itself increase. It is further divided into: nervous system diseases and non-muscle non-nervous system diseases.
4. Etiology of HyperCKemia
The etiology of hyperCKemia is mainly divided into the following three categories: primary disease of muscle tissue, primary disease of nervous system (secondary muscle) and non-muscular non-nervous primary diseases.
(click to enlarge)5. • serum CK value 1.5 times higher than ULN (diagnosis of hyperCKemia); • Exclude one by one non-neuromuscular and non-myopathic diseases that can lead to elevated serum CK values;• Find out neurological diseases that cause CK elevation; • If non-myopathic hyperCKemia is completely excluded, consider Primary myogenic disease (according to the diagnostic algorithm for mild/asymptomatic hypercreatine kinaseemia); • 1 month interval Recheck the serum CK value (avoid strenuous exercise 7 days before the test) to confirm the persistence of hyperCKemia and exclude the increase of serum CK value caused by normal exercise;< span>• Nerve conduction and EMG if reexamination confirms hyperCKemia; • muscle Biopsy: Muscle biopsy should be considered in the following cases: abnormal electromyography suggesting myogenic changes, serum CK value 3 times higher than normal, age younger than 25 years, concurrent exercise-induced myalgia or exercise intolerance, and serum CK value is not consistent. to 3 times normal for women; • on the role of EMG, except for rare conditions such as tonicity With the exception of muscular dystrophy, EMG usually does not provide diagnostic information other than motor unit physiology. The guideline believes that in the case of normal EMG, the diagnostic value of muscle biopsy is small. In other words: EMG has a higher negative predictive value. 
< Long-term prognosis of patients with mildly symptomatic/asymptomatic hyperCKemiaCurrent clinical research results suggest that the long-term prognosis of patients with mildly symptomatic/asymptomatic hyperCKemia is good.
Go back to the beginning 2Cases:
• First, both non-neuromuscular and non-myopathic diseases could be ruled out, thus, consistent with the diagnosis of mild/asymptomatic hyperCKemia;
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• Secondly, according to the diagnostic process, it is recommended to review CK after 1 month.
Case 1 was followed up for 1 month, but still had no clinical symptoms, reexamination CK < 1.5 ULN, no special treatment, long-term follow-up CK returned to normal Level.
Case 2 After 1 month, the symptoms of fatigue gradually eased, CK < 3 ULN was re-examined, and electromyography was performed: double The muscles and nerve conduction functions of the upper limbs are normal, except for mild myogenic damage to the muscles of the lower limbs? Without special treatment, the patient's symptoms of fatigue gradually eased, and CK gradually returned to normal level after 3 months of follow-up.
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For these two cases, we also have some doubts. Both of these two patients have stopped statin for more than 1 month, and the CK is still elevated, so we ruled out the elevated CK caused by statin. During the later follow-up, the CK levels of both patients decreased and gradually returned to normal levels. However, considering the risk of recurrent CK elevation when taking statins again, neither patient was given CK again. For statin therapy, he switched to ezetimibe for lipid-lowering therapy. The second patient was advised to use PCSK9 inhibitor for lipid-lowering therapy because of stent implantation. Have you encountered similar cases? How is it handled? The first publication of this article: ZZ reading the literature, thanks for the authorizationTypesetting: lySubmission: [email protected]Source of title map: Zhanku HailuoReferences:
1. Li Jianping. Interpretation and latest progress of the guidelines for the diagnosis of mildly symptomatic/asymptomatic hypercreatine kinase hyperemia[J]. Journal of Neurology and Neurorehabilitation. 2016.12(2):64-70
2. T. Kyriakides, et.al EFNS guidelines on the diagnostic approach to pauci- or asymptomatic hyperCKemia.[J].European Journal of Neurology.2010,17: 767–773< /p>