What are the normal levels of Troponin I (Trop I) and Creatine Kinase-MB (CKMB)?

Normal Troponin I and CKMB Levels

The upper limit of normal for troponin I is defined as the 99th percentile of a healthy reference population, which typically ranges from 0.01-0.04 ng/mL for conventional assays (or 10-20 ng/L for high-sensitivity assays), while CKMB normal values are generally <3.9-6.7 ng/mL depending on the assay used. 1, 2, 3

Troponin I Reference Ranges

Assay-Dependent Cutoffs:

• The 99th percentile cutoff is the recommended threshold and varies by specific assay manufacturer 1, 2
• Conventional troponin I assays: typically 0.01-0.04 ng/mL (or <0.1 ng/mL for some assays) 2, 3
• High-sensitivity cardiac troponin assays: 10-20 ng/L for adults 2, 4
• Cardiac troponins are generally undetectable in healthy individuals 1, 2

Critical Technical Requirements:

• The assay must have a coefficient of variation ≤10% at the 99th percentile level 1, 2
• Point-of-care devices are often less sensitive than central laboratory analyzers and may miss minor elevations 2, 4

CKMB Reference Ranges

Standard Cutoffs:

• Normal CKMB is typically <3.9-6.7 ng/mL depending on the specific assay 3, 5
• The 99th percentile cutoff for CKMB is approximately 3.9 ng/mL 3
• CKMB rises to 2-5 times the upper limit of normal after acute MI and returns to normal within 2-3 days 1

Age-Specific Considerations

Pediatric Populations:

• Troponin I values are generally <2.0 ng/mL in children and frequently below the detection limit of 1.5 ng/mL 6
• Pediatric reference ranges are lower than adult values for children beyond infancy 4

Elderly Patients:

• Age substantially affects troponin concentrations, with differences up to 300% between healthy young versus elderly individuals 7
• Chronic mild elevations are common in elderly patients with structural cardiac abnormalities and renal insufficiency 7

Critical Interpretation Pitfalls

Timing Matters:

• Troponins can be detected as early as 2-4 hours after symptom onset but elevation can be delayed up to 8-12 hours 1, 2
• A normal troponin on initial presentation does not exclude myocardial infarction—serial testing at 3 and 6 hours is necessary 2
• Troponin levels may stay elevated for 7 days or more after acute MI 1

Non-Ischemic Causes of Elevation:

• Troponin elevation indicates cardiac injury but not necessarily ischemic injury 2
• Alternative causes include heart failure, myocarditis, pulmonary embolism, sepsis, renal failure, cardiac trauma, tachyarrhythmia, and pericarditis 1, 2

Discordant Results:

• At the 99th percentile cutoffs, approximately 12.2% of troponin I-positive cases may be CKMB-negative 3
• CKMB-positive/troponin I-negative cases (8.8%) are likely false positives for myocardial injury 3

Clinical Decision Algorithm

For Suspected Acute Coronary Syndrome:

1. Obtain baseline troponin I (preferred over CKMB due to superior specificity) 1, 3
2. Repeat at 3-6 hours if initial value is normal or near the 99th percentile 2
3. A rising pattern (≥20% change) with at least one value above the 99th percentile indicates acute myocardial injury 7
4. Small increases in troponin below the upper limit of normal (>15% of institutional cutoff) are associated with increased odds of acute coronary syndrome 8