Creatine kinase (CK-MB) is an enzyme predominantly found in cardiac tissue, where it plays a role in energy generation. It is released into the bloodstream when cardiac muscle damage occurs, making it a marker for conditions like myocardial infarction and cardiac ischemia. Elevated CK-MB levels can also result from cardiac procedures, intense physical activity, or muscle diseases such as inflammatory myopathy and muscular dystrophy.
While CK-MB was once a primary marker for diagnosing heart attacks, it has largely been replaced by troponins, which are more specific to heart muscle damage. However, CK-MB is still useful in assessing cardiac injury after interventions like percutaneous coronary intervention (PCI), where elevated levels indicate significant atherosclerotic burden or procedural damage. A low CK-MB suggests the absence of cardiac muscle damage.
Standard Range: 0-5.0 ng/mL
The ODX Range: 0-5.0 ng/mL
Low CK-MB is likely associated with the absence of acute myocardial injury.
High CK-MB is associated with acute MI, cardiac ischemia, surgery, arrhythmias, defibrillation, cardioversion, inflammatory myopathy, muscular dystrophy (Pagana 2024), intense exercise, myocarditis, skeletal muscle disorders (Kurapati 2023), and proportionally increased risk of mortality following MI (Alexander 2000). A higher CK-MB following PCI intervention correlates with a more significant atherosclerotic plaque burden (Mehran 2000).
The enzyme creatine kinase (CK) catalyzes the reversible phosphorylation of creatine, helping to generate energy [ADP + creatine phosphate yields ATP + creatine]. It is found in muscle and released into circulation when muscle is injured or diseased. Creatine kinase occurs in three isoforms: CK-MM, CK-MB, and CK-BB. The highest concentrations of CK-MM are in skeletal muscle, CK-BB in the nervous system, and CK-MB in cardiac muscle, which contains 15-30% CK-MB and 70-85% CK-MM. Levels of CK-MB in serum are usually 3-5% of the total CK in circulation. CK-MB levels rise within 4-6 hours of an acute myocardial infarction (AMI), peak at 24 hours, and should return to normal within 48-72 hours, even if total CK remains elevated. However, CK-MB measurement has widely been replaced by troponins for diagnosing MI. Troponins have a longer half-life and are more specific to cardiac muscle than CK-MB. Troponins are preferred due to the limitations associated with CK-MB, which can become elevated in non-cardiac conditions (Kurapati 2023).
CK-MB levels can increase following percutaneous coronary intervention (PCI) when associated with an increased atherosclerotic burden (Mehran 2000) or due to damage incurred by the procedure itself, which can increase cardiovascular event and mortality risk. Vitamin C given before interventional procedures may reduce cardiac damage and decrease CK-MB levels. A meta-analysis of 7 trials comprising 827 patients found that 1-16 grams of vitamin C administered before the procedure significantly reduced CK-MB, troponins, and biomarkers of oxidative stress. Vitamin C protects the myocardium, preserves endothelial function, improves myocardial perfusion and left ventricular ejection fraction, and prevents postop atrial fibrillation in high-risk patients (Rozemeijer 2023).
CK-MB levels can also increase with skeletal muscle damage. Evaluating the CK Index can help differentiate skeletal muscle damage from an acute MI. The CK index calculation entails CK-MB ng/mL X 100 / total CK activity IU/L. A CK Index above 2.5 with an elevated CK-MB suggests cardiac damage (Testing.com). An elevated CK Index may be considered predictive of AMI. A retrospective study of 196 AMI subjects found significantly higher CK Index, CK, CK-MB, neutrophils, and neutrophil:lymphocyte ratio were associated with AMI versus controls (Liu 2024).
Persistently elevated CK-MB and CK Index following resolution of cardiac symptoms should be investigated further. The commonly used immunoinhibition method of measuring CK-MB may yield falsely elevated readings. Further CK-MB testing using electrophoresis or immunoprecipitation before immunoinhibition testing may resolve this anomaly (Ghosh 2023).
CK-MB may be measured with a high-sensitivity method, yielding an hsCK-MB result. This method may be useful in predicting all-cause mortality in stable coronary heart disease where an hsCK-MB of 4.73 ng/mL or above had a two-fold higher risk of a primary cardiovascular event than a lower level (Wu 2020).
Note: CK-MB exists in two forms: CK-MB1 and CK-MB2. The tissue form, CK-MB2, is released from cardiac muscle following an AMI and rapidly converted to CK-MB1 in the serum. The ratio of CK-MB2 to CK-MB1 is usually below 1. A ratio above 1.7 suggests AMI (Kurapati 2023).
Alexander, J H et al. “Association between minor elevations of creatine kinase-MB level and mortality in patients with acute coronary syndromes without ST-segment elevation. PURSUIT Steering Committee. Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy.” JAMA vol. 283,3 (2000): 347-53. doi:10.1001/jama.283.3.347
Ghosh, Abhra et al. “Higher Levels of Creatine Kinase MB (CK-MB) Than Total Creatine Kinase (CK): A Biochemistry Reporting Error or an Indicator of Other Pathologies?.” Cureus vol. 15,12 e50792. 19 Dec. 2023, doi:10.7759/cureus.50792
Kurapati, Rahul. and Michael P. Soos. “CPK-MB.” StatPearls, StatPearls Publishing, 7 April 2023
Liu, Yin et al. “Diagnostic value of the creatine kinase-MB/creatine kinase and neutrophil/lymphocyte ratios in acute myocardial infarction.” Journal of cardiothoracic surgery vol. 19,1 227. 16 Apr. 2024, doi:10.1186/s13019-024-02740-9
Mehran, R et al. “Atherosclerotic plaque burden and CK-MB enzyme elevation after coronary interventions : intravascular ultrasound study of 2256 patients.” Circulation vol. 101,6 (2000): 604-10. doi:10.1161/01.cir.101.6.604
Pagana, Kathleen Deska, et al. Mosby’s Diagnostic and Laboratory Test Reference. 17th ed., Mosby, 2024.
Rozemeijer, Sander et al. “Vitamin C may reduce troponin and CKMB levels after PCI and CABG: a meta-analysis.” BMC cardiovascular disorders vol. 23,1 475. 21 Sep. 2023, doi:10.1186/s12872-023-03459-6
Wu, Yen-Wen et al. “Potential impacts of high-sensitivity creatine kinase-MB on long-term clinical outcomes in patients with stable coronary heart disease.” Scientific reports vol. 10,1 5638. 27 Mar. 2020, doi:10.1038/s41598-020-61894-3