CK-MB Relative Index: how to calculate the CK-MB/total CK fraction and why troponin is preferred
What the CK-MB relative index shows and when it is used
Creatine kinase (CK) is an enzyme of muscle energy metabolism. It circulates as three main isoenzymes: CK-MM, predominant in skeletal muscle; CK-MB, more abundant in the myocardium; and CK-BB, from the brain and some smooth tissues. Total CK is the sum of all of them.
The relative index calculates how much CK-MB represents relative to total CK. The idea is that, in a CK elevation of cardiac origin, the MB fraction tends to be larger than in an elevation of skeletal muscle origin, in which CK-MM dominates.
The role of this calculation has changed. The 2021 guidelines of the Brazilian Society of Cardiology and the 2023 guidelines of the European Society of Cardiology define cardiac troponin as the biomarker of choice when myocardial infarction is suspected. Today the index appears more in the workup of elevated CK, for example after trauma or surgery, and when analytical interference is suspected. Since AST also rises in muscle injury, the AST/ALT ratio is often evaluated alongside it.
How to calculate the index in the calculator: inputs and units
The calculator asks for three pieces of information from the same sample:
- Total CK, in U/L.
- How CK-MB was measured: mass, in ng/mL (default option), or activity, in U/L.
- CK-MB, as the value on the report.
The tool divides CK-MB by total CK and multiplies by 100. The result appears with two decimal places.
Values equal to or below zero produce an error message. With both measurements in U/L, a CK-MB greater than total CK also produces an error, because it is physiologically impossible and indicates interference.
The choice of method matters. With CK-MB mass, the index mixes ng/mL with U/L and is therefore not a true percentage, but it is the form for which the cutoffs of 2.5 to 3 were described. With CK-MB activity, the number is the real percentage of total CK, and the tool shows the value without classifying it.
Relative index formula and definition of terms
The calculation is the same for both CK-MB methods; what changes is the reading.
CK-MB relative index = [CK-MB ÷ Total CK (U/L)] × 100
- CK-MB mass: concentration of the MB protein, in ng/mL, measured by immunoassay with antibodies against the MB molecule.
- CK-MB activity: activity of the isoenzyme, in U/L, usually measured by immunoinhibition, which blocks the M subunit and measures the remaining activity.
- Total CK: activity of all CK isoenzymes in the sample, in U/L.
Immunoinhibition has a known limitation: it attributes to CK-MB all the activity linked to the B subunit. Therefore, CK-BB and macroenzymes are counted as if they were CK-MB. Schifferli and colleagues (1986) described 14 patients with falsely elevated CK-MB by this mechanism, so-called macro-CK type 1.
The name “CK/CK-MB ratio” suggests the inverse division, but the useful calculation, and the one the tool performs, is CK-MB over total CK.
Worked example of the CK-MB relative index
Consider hypothetical data, only to check the calculation: total CK of 800 U/L and CK-MB mass of 30 ng/mL, in the same sample.
- Divide CK-MB by total CK: 30 ÷ 800 = 0.0375.
- Multiply by 100: 0.0375 × 100 = 3.75.
- With two decimal places: relative index = 3.75.
Since the value exceeds 3, the calculator reports that the CK-MB may be of myocardial origin. With total CK of 1,000 U/L and CK-MB mass of 20 ng/mL, the index would be 2.00, below 2.5, and the tool would say that the pattern does not suggest myocardial origin.
If the same sample had a CK-MB activity of 60 U/L, the result would be 7.50%, shown without classification, because the cutoffs of 2.5 to 3 do not apply to activity.
None of these numbers confirms or rules out myocardial infarction. Management depends on troponin, the electrocardiogram and the clinical picture.
How to understand the result: cutoffs of 2.5 to 3
With CK-MB mass, the calculator uses the cutoffs of 2.5 to 3 adopted by clinical laboratories. They are described in reference material for patients and professionals (Testing.com, 2021):
- Below 2.5: does not suggest CK-MB of myocardial origin; with elevated total CK, the pattern is compatible with skeletal muscle origin.
- From 2.5 to 3: borderline range between the cutoffs used.
- Above 3: suggests that the CK-MB may be of myocardial origin.
The index only makes sense when total CK and CK-MB are elevated. With normal values, small variations change the number a lot. Since skeletal muscle also contains CK-MB, extensive muscle injury can mask simultaneous cardiac injury.
With CK-MB activity, there is no general-use cutoff, and very high percentages raise the hypothesis of interference. Rosa-Jiménez and colleagues (1997) described that, with immunoinhibition, macro-CK usually produces CK-MB above 50% of total activity. Interpretation is the responsibility of the professional, together with the clinical picture and other tests.
Common errors and verification checklist
The most common errors with this index come from the inverted name, the wrong choice of method and analytical interference.
- Inverting the calculation: the old name suggests CK ÷ CK-MB, but the index is CK-MB ÷ CK × 100.
- Selecting the wrong method: CK-MB in ng/mL is mass; in U/L it is activity. The cutoffs of 2.5 to 3 apply only to mass.
- Calculating with normal total CK: the index loses meaning.
- Ignoring macro-CK: very high CK-MB activity, especially with normal total CK, suggests interference rather than injury.
- Using samples from different times: CK and CK-MB have their own kinetics; both must come from the same collection.
Checklist:
- Are both measurements from the same sample?
- Does the selected method match the unit on the report?
- Is total CK elevated?
- With activity, did the percentage exceed 50% or 100%? If so, consider interference and confirm with isoenzyme electrophoresis or CK-MB mass.
- Was troponin measured, when the question is cardiac?
Limitations and comparison with troponin
The CK-MB relative index has limitations that restrict its current use. CK-MB is not exclusive to the heart, the cutoffs vary between methods and immunoinhibition confuses CK-BB and macroenzymes with CK-MB.
| Marker | Current role | Note |
|---|---|---|
| Troponin (I or T), preferably high-sensitivity | Biomarker of choice when myocardial infarction is suspected (SBC 2021; ESC 2023) | With troponin available, no other marker is needed for diagnosis |
| CK-MB mass and relative index | Alternative when troponin is not available (SBC 2021) | Index above 2.5 to 3 suggests myocardial origin of CK-MB |
| CK-MB activity | Not mentioned in the 2021 recommendations | Subject to interference from macro-CK and CK-BB |
| Total CK | Marker of skeletal muscle injury | Low specificity for the heart |
In extensive muscle injury, such as rhabdomyolysis, the concern shifts to the kidney, and the glomerular filtration rate estimated by CKD-EPI helps with monitoring. For long-term cardiovascular risk, the lipid panel, with LDL cholesterol, plays a more relevant role than CK.
Frequently asked questions about the CK-MB relative index
Does the calculator divide CK by CK-MB or CK-MB by CK?
CK-MB by total CK, multiplied by 100. That is the CK-MB relative index; the old name “CK/CK-MB ratio” suggested the inverse division.
Can I use CK-MB mass in ng/mL?
Yes, and it is the default option. The cutoffs of 2.5 to 3 were described for CK-MB mass divided by total CK in U/L. In this case the index is not a true percentage, because it mixes units.
What relative index suggests cardiac origin?
With CK-MB mass, laboratories use cutoffs of 2.5 to 3: above that, CK-MB may be of myocardial origin; below, with elevated CK, skeletal muscle origin is more likely. The index only applies with elevated CK and CK-MB.
What does a CK-MB greater than total CK mean?
With both in U/L, it is physiologically impossible and indicates analytical interference, such as macro-CK type 1. The calculator shows an error in this case. The laboratory can clarify with isoenzyme electrophoresis or CK-MB mass.
Does the CK-MB relative index diagnose myocardial infarction?
No. The guidelines of the Brazilian Society of Cardiology (2021) and the European Society of Cardiology (2023) define troponin as the biomarker of choice when myocardial infarction is suspected. The index is supporting data, interpreted by the professional.
References
- Nicolau JC, Feitosa Filho GS, Petriz JL, Furtado RHM, Précoma DB, Lemke W, et al. Diretrizes da Sociedade Brasileira de Cardiologia sobre Angina Instável e Infarto Agudo do Miocárdio sem Supradesnível do Segmento ST – 2021. Arq Bras Cardiol. 2021;117(1):181-264. View
- Byrne RA, Rossello X, Coughlan JJ, Barbato E, Berry C, Chieffo A, et al. 2023 ESC Guidelines for the management of acute coronary syndromes. Eur Heart J. 2023;44(38):3720-3826. View
- Testing.com. CK-MB. Updated 2021 Nov 9 [accessed 2026 Oct 25]. View
- Schifferli JA, Despont JP, Cruchaud A, Carpentier N, Jeannet M, Schmidt M. Macro-creatine kinase type 1. Immunological studies in 14 patients with comments on clinical significance. Arch Pathol Lab Med. 1986;110(5):425-9. View
- Rosa-Jiménez F, Gassó de Campos M, Camacho Reina MV, Vázquez de Castroviejo E, Hernández Burruezo JJ, Pousibet Sanfeliú H. Macro creatine kinase type 1 as a cause of increase of CK-MB isoenzyme. Apropos of 7 cases. Rev Esp Cardiol. 1997;50(3):166-72. View
Updated . A support tool for educational purposes; it does not replace clinical assessment.