Normal CK-MB Reference Range
The normal upper limit for CK-MB is defined as the 99th percentile of a sex-specific reference control population, which must be determined by each laboratory using their specific assay. 1
Defining the Reference Range
The diagnostic threshold for CK-MB must be established using the 99th percentile of at least 120 healthy individuals without known heart disease, stratified by sex. 2
Sex-specific reference limits are mandatory because men typically have 2- to 3-fold higher CK-MB values than women due to greater muscle mass. 1, 2
Laboratories should also consider establishing ethnic-specific reference ranges, as African Americans may demonstrate 2- to 3-fold higher CK-MB concentrations compared to Caucasians due to physiological differences in muscle mass. 1
The assay's total imprecision (coefficient of variation) must be ≤10% at the 99th percentile to ensure reliable clinical decision-making. 1, 2
Typical Numeric Values
CK-MB mass is reported in ng/mL, with diagnostic thresholds typically ranging from ≥5 ng/mL to ≥8 ng/mL depending on the specific assay and sex. 2
The European Society of Cardiology references a CK-MB mass threshold of ≥5 ng/mL for diagnosing myocardial infarction, though this varies by assay. 2
Some clinical contexts use a threshold of ≥8 ng/mL, particularly for male populations. 2
Critical Diagnostic Requirements
Two consecutive measurements of CK-MB above the 99th percentile are required to establish sufficient biochemical evidence of myocardial necrosis, given CK-MB's lower tissue specificity compared to troponin. 1, 3
A characteristic rise and/or fall pattern provides additional evidence supporting acute myocardial injury and helps distinguish acute events from chronic elevations or skeletal muscle sources. 1, 2, 3
Important Caveats
Each laboratory must validate their own reference range using their specific assay platform, as there is no standardization across CK-MB assays and manufacturers' package inserts often differ from peer-reviewed literature. 1
CK-MB comprises 1-3% of total CK in skeletal muscle and is also present in intestine, diaphragm, uterus, and prostate, meaning elevations can occur from non-cardiac sources. 4
When CK-MB is elevated but cardiac troponin remains below the 99th percentile, investigate non-cardiac etiologies (skeletal muscle injury, rhabdomyolysis, intestinal injury, post-surgical states) before attributing the elevation to myocardial infarction. 3, 4
Cardiac troponin is now the preferred biomarker over CK-MB for diagnosing myocardial infarction due to superior cardiac specificity and sensitivity; CK-MB should only be used when troponin is unavailable. 1, 3
Kinetics and Timing
CK-MB begins to rise within 3-4 hours after myocardial injury onset, peaks at 12-24 hours, and returns to normal within 48-72 hours. 1, 2, 3
This shorter half-life makes CK-MB particularly useful for detecting early reinfarction within 48-72 hours of an index MI, when troponin remains elevated for 7-14 days. 1, 3