Many discordant troponin results are macrotroponin, not myocardial injury

Design

Population cohort with biochemical verification in a subset and replication in a second cohort

Population

19,499 adults with both troponin I and T measured; macrotroponin verified in 203 samples

Primary outcome

Myocardial infarction, ischaemic stroke or cardiovascular death

Effect

True injury: adjusted HR 2.90 (troponin I) and 1.99 (troponin T); suspected macrotroponin: HR 1.59 (0.94 to 2.70) and 1.27 (1.00 to 1.61)

In a general-population cohort of 19,499 people (median age 49, 58.3% women) with both troponin I and T measured, elevated troponin I was found in 1% and elevated troponin T in 6%. Among those elevated, 48% and 57% were discordant between the two assays, defined as more than a threefold difference in concentration.

In a subset of 203 samples tested biochemically, 92.5% of discordant troponin I and 15.4% of discordant troponin T results were due to macrotroponin complexes, in which antibodies bind troponin and distort the assay or its clearance. People with concordant elevation, meaning true myocardial injury, had higher risk of myocardial infarction, ischaemic stroke or cardiovascular death (adjusted HR 2.90 for troponin I, 1.99 for troponin T). Those with suspected macrotroponin had risks closer to people with normal values (troponin I 1.59, 95% CI 0.94 to 2.70; troponin T 1.27, 1.00 to 1.61). The pattern was similar in a second cohort.

This was a general-population study, not an emergency department one, and the risk estimates concern long-term events. The practical lesson is that a persistent, unexplained raised troponin, especially troponin I, can be an artefact worth checking before further investigation.

• Suspect assay interference when a raised troponin is persistent, flat and unexplained by symptoms.
• If both troponin I and T are available, compare them; a large discordance should raise the question.
• Ask your laboratory whether it can test for macrotroponin or re-run the sample on another platform.
• Do not use a raised troponin alone to label a patient as high risk before interference is considered.
• Treat concordant elevation as real myocardial injury and look for the cause.

Why it matters

It challenges the assumption that every raised troponin reflects myocardial injury, particularly when used for risk prediction in people without acute symptoms.

Don't overread it

This was a general-population risk-prediction cohort; it does not change how a rising and falling troponin is interpreted in suspected acute coronary syndrome.

The statistics, in plain English

A hazard ratio of 2.90 means about three times the rate of events over follow-up compared with people without elevated troponin. For suspected macrotroponin the interval for troponin I (0.94 to 2.70) includes 1.0, so no excess risk was shown, though the numbers were small. The confirmation by immunoglobulin depletion was done only in a subset of 203 samples.

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