Additional Biomarkers to Assess Elevated Creatine Kinase

Initially, the risk of myocardial infarction, muscle injury, or strenuous exercise must be evaluated further in someone with elevated creatine kinase.

Creatine kinase (CK), also known as creatine phosphokinase (CPK), represents a group of enzymes found in high-energy tissues. More than 99% of CK is found in skeletal muscle but it is also found in the heart and brain. Levels increase with inflammation or damage to these tissues within 6 hours of insult and usually return to normal within three to seven days.

The test had been commonly used to diagnose myocardial infarction, in which case isoenzymes must be measured to identify their source: CK-MM from muscle, CK-MB from cardiac tissue, and CK-BB from the brain. A mild elevation in CK may be seen with unstable angina without an MI. However, measuring cardiac troponin levels is preferred over CK measurements for diagnosing MI (Pagana 2022).

Elevated CK levels can also be seen with:

• Increased mortality risk after surgery (Levy 2011)
• Osteoarthritic disorders (Ganguly 2019)
• Severe hypertension, especially 313.92 U/L (5.23 ukat/L) and above (Sukul 2018)
• Exercise and strength training; levels can increase to 400-700 U/L (6.7-11.7 ukat/L), though a maximum of 300-500 U/L (5.01-8.35 ukat/L) is recommended for endurance exercise to obtain maximum exercise benefit (Lam 2019).
• Excessive strength training and sports rhabdomyolysis can increase CK levels above 1,000 U/L (16.7 ukat/L). Such high levels can cause abnormal heart rhythms, kidney failure, and death (Backer 2020)
• Heavy manual labor can increase CK levels by 30 times the upper limit but should decline within 7 days (Moghadam-Kia 2016).
• Certain medications, including alcohol, aspirin, statins, and antibiotics (Pagana 2022)

Additional biomarkers to assess when CK is elevated:

• If myocardial infarction, cardiac damage, and excessive exercise are ruled out and elevated CK levels persist, additional assessments should begin with serum electrolytes, especially potassium, thyroid function, liver function, kidney function, and inflammation.
• Measuring CK-MM, C-reactive protein, and aldolase can be helpful in assessing osteoarthritic disorders (Ganguly 2019).
• CK levels 1.5 times above the upper end of the lab range should be evaluated for an association with metabolic dysfunction, endocrine disorders, malignancy, drug effects, and, finally, neuromuscular causes if elevations persist (Moghadam-Kia 2016).
• Elevated CK and LDH together may be indicative of malignancy and should be evaluated further (Pujara 2017).

References

Backer, Henrik Constantin et al. “Exertional rhabdomyolysis and causes of elevation of creatine kinase.” The Physician and sportsmedicine vol. 48,2 (2020): 179-185. doi:10.1080/00913847.2019.1669410

Ganguly, Apurba. “Levels of C-reactive protein, creatine kinase-muscle and aldolase A are suitable biomarkers to detect the risk factors for osteoarthritic disorders: A novel diagnostic protocol.” Caspian journal of internal medicine vol. 10,1 (2019): 25-35. doi:10.22088/cjim.10.1.25

Lam, Fui-Ching et al. “Effectiveness of whey protein supplements on the serum levels of amino acid, creatinine kinase and myoglobin of athletes: a systematic review and meta-analysis.” Systematic reviews vol. 8,1 130. 31 May. 2019, doi:10.1186/s13643-019-1039-z

Levy, Michael et al. “Prognostic value of troponin and creatine kinase muscle and brain isoenzyme measurement after noncardiac surgery: a systematic review and meta-analysis.” Anesthesiology vol. 114,4 (2011): 796-806. doi:10.1097/ALN.0b013e31820ad503

Moghadam-Kia, Siamak et al. “Approach to asymptomatic creatine kinase elevation.” Cleveland Clinic journal of medicine vol. 83,1 (2016): 37-42. doi:10.3949/ccjm.83a.14120

Pagana, Kathleen Deska, et al. Mosby's Diagnostic and Laboratory Test Reference. 16th ed., Mosby, 2022.

Pujara, Nishant and ana Chaudhary. “Evaluation of creatine kinase and lactate dehydrogenase for liver abnormalities: a biochemical study.” International Journal of Advances in Medicine 4 (2017): 1355-1357.

Sukul, Surankita, et al. "Serum Creatine Kinase Activity among Hypertensive Patients and its Role as a Predictor for Failure of Antihypertensive Treatment." Journal of Clinical & Diagnostic Research 12.11 (2018).

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