CK-MB

Creatine kinase MB (CK-MB) is the cardiac enriched isoenzyme of creatine kinase, a dimer of M and B subunits. Myocardium contains 15 to 40% CK-MB, compared with under 3% in skeletal muscle (apart from regenerating muscle). It is measured as a mass concentration by immunoassay (CK-MB mass, ng/mL or microg/L), which is more sensitive and specific than activity assays.

Since high sensitivity troponin assays became available, CK-MB is no longer the preferred marker for myocardial infarction. It keeps a role in dating a recent infarct and detecting reinfarction in the first days, in settings without troponin, and in some periprocedural monitoring.

Skeletal muscle disease, renal failure and strenuous exercise raise CK-MB without cardiac injury. CK-MB rises 3 to 6 hours after myocardial injury, peaks at 12 to 24 hours and returns to normal in 48 to 72 hours. This short window makes it useful for detecting a second event after troponin has already risen, because troponin stays raised for 7 to 14 days. In many countries it is still used as a second line test, and the relative index (CK-MB mass divided by total CK) helps to separate cardiac from skeletal sources.

Indications. Suspected recurrent myocardial infarction within 2 to 7 days of a first event. Settings where troponin is not available. Assessment of the timing of infarction. Monitoring after cardiac surgery or percutaneous intervention in some units. Suspected myocardial injury in the presence of chronically raised troponin (such as renal failure). Differentiating the source of a raised total creatine kinase.

Specimen. Serum or lithium heparin plasma, 1 to 2 mL, no fasting. Stable for 24 hours at room temperature and 7 days at 2 to 8 °C. Serial samples at presentation, 3 to 6 hours and 12 hours show the rise and fall. Haemolysis should be avoided.

Reference values (assay dependent).

• CK-MB mass: under 5 ng/mL (microg/L) in men and under 3.6 ng/mL in women, with the 99th percentile of a healthy reference population as the decision limit.
• Relative index: CK-MB mass (ng/mL) divided by total CK activity (U/L), multiplied by 100. Under 2.5 suggests skeletal source. Over 3 suggests cardiac source (value method dependent).
• CK-MB activity (older assays): under 25 U/L, or under 6% of total CK on electrophoresis.

Interpretation.

• Rise over the decision limit with a typical rise and fall pattern, together with symptoms or ECG change: myocardial infarction, when troponin is not available.
• A second rise after a fall in a patient with a recent infarct: reinfarction or extension.
• Raised total CK with a CK-MB index under 2.5: skeletal muscle injury.
• Persistently raised CK-MB with a low index: macro-CK, regenerating muscle, malignancy (CK-BB, not MB), or rhabdomyolysis.
• Troponin positive with normal CK-MB: small infarcts, myocarditis, heart failure, pulmonary embolism, sepsis, renal failure and strenuous exercise.
• CK-MB raised without troponin: skeletal muscle (especially after exercise, in athletes, polymyositis or muscular dystrophy), myocarditis with limited troponin change (rare), and false positives.

Time course.

Limits of use. Sensitivity for myocardial infarction at presentation is 40 to 60%, rising to 90 to 95% at 6 to 12 hours. Specificity is 80 to 90%. High sensitivity troponin detects injury earlier and with greater accuracy, and the use of CK-MB in addition adds no diagnostic value for most patients.

Critical values and findings needing immediate action.

• A rising CK-MB in a patient with chest pain or ECG change: urgent cardiology assessment for possible acute coronary syndrome.
• A new CK-MB rise after an initial fall in the days after infarction: suspected reinfarction, repeat ECG and imaging.
• Total CK over 5000 U/L with a low CK-MB index and dark urine: rhabdomyolysis, aggressive fluid therapy and monitoring of potassium, calcium and creatinine.
• Severe hyperkalaemia with raised CK: urgent cardiac monitoring.

Interferences and pitfalls.

• Skeletal muscle injury (intramuscular injections, trauma, exercise, seizures, surgery, myositis, rhabdomyolysis, hypothyroidism, statin myopathy) raises CK-MB.
• Chronic renal failure causes a persistent rise in CK-MB and total CK.
• Macro-CK (type 1 complexed with immunoglobulin, type 2 mitochondrial) gives falsely high CK-MB activity on some assays.
• Heterophile antibodies, haemolysis and bilirubin interfere with immunoassays.
• Early presenters (under 3 hours of symptoms) may have normal values.
• Cardiac surgery, cardioversion, defibrillation and myocarditis raise CK-MB without infarction.
• Cardiac sources of CK-MB include regenerating skeletal muscle and some tumours, and the relative index is not reliable when total CK is very high.
• CK-MB mass assays differ between manufacturers, and results are not interchangeable.

Special groups.

• Athletes: CK-MB rises after endurance exercise, with a normal troponin.
• Neonates: CK-MB is physiologically high in the first days of life.
• Older adults: sarcopenia lowers the baseline, and falls with intramuscular injury raise it.
• Regions: where troponin assays are not available, serial CK-MB with ECG remains the main biochemical aid.

Follow up tests. High sensitivity cardiac troponin, total creatine kinase, serial ECG, echocardiography, creatinine and electrolytes, myoglobin, lactate dehydrogenase, lipid profile, HbA1c, and coronary angiography as indicated.