TY - JOUR
T1 - Influence of Macrotroponin on the 99th Percentile Threshold in 2 High-Sensitivity Cardiac Troponin Assays
AU - Strandkjær, Nina
AU - Hansen, Morten Bagge
AU - Afzal, Shoaib
AU - Hasselbalch, Rasmus Bo
AU - Knudsen, Sophie Sander
AU - Kristensen, Jonas Henrik
AU - Kronborg, Alexander Holst
AU - Kamstrup, Pia Rørbæk
AU - Kobylecki, Camilla Jannie
AU - Hilsted, Linda Maria
AU - Dahl, Morten
AU - Overgaard, Martin
AU - Banerjee, Aditi
AU - Ladefoged, Søren Andreas
AU - Bundgaard, Henning
AU - Jaffe, Allan S
AU - Iversen, Kasper Karmark
AU - Hammarsten, Ola
N1 - © Association for Diagnostics & Laboratory Medicine 2025. All rights reserved. For commercial re-use, please contact [email protected] for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact [email protected].
PY - 2025/8/1
Y1 - 2025/8/1
N2 - BACKGROUND: Cardiac troponin (cTn) levels exceeding the 99th percentile upper reference limit and a rise/fall pattern are key for diagnosing myocardial injury and infarction. Macrotroponins, formed by patient anti-cTn antibodies targeting cTn, can cause persistently elevated cTn levels without ongoing myocardial injury. The frequency and impact of macrotroponin interference on cTn 99th percentiles are unclear. This study compares sex-specific 99th percentiles for 2 cTn assays, before and after excluding macrotroponin-positive samples, focusing on the top 10% of cTn levels.METHODS: We examined 1058 plasma samples from healthy individuals previously used for Danish cTn 99th percentiles. Following International Federation of Clinical Chemistry and Laboratory Medicine educational recommendations, macrotroponin presence was assessed in the top 10% cTn samples using immunoglobulin G (IgG) depletion screening and a reference sucrose gradient, confirming macrotroponin when both methods concurred. Due to analytical dilution constraints, [the highest] 88 of 135 Siemens Atellica high-sensitivity cTnI (hs-cTnI) samples were analyzed with both methods. All 106 Roche hs-cTnT samples were negative using IgG depletion, and sucrose analysis was limited to the highest 70 samples.RESULTS: Macrotroponin was found in 76% (67/88) of Siemens samples but in none of the Roche samples (0/70). Excluding macrotroponin-affected samples lowered the Siemens 99th percentiles from 117 ng/L to 22 ng/L in men and from 37 ng/L to 9 ng/L in women. The 99th/50th percentile ratio for Siemens decreased from 12- to 29-fold to 3- to 7-fold, approaching the Roche ratios.CONCLUSIONS: Macrotroponin significantly influenced the Siemens Atellica hs-cTnI 99th percentiles, suggesting important clinical implications that warrant further prospective studies. The 99th/50th percentile ratio may help evaluate macrotroponin interference in troponin assays.
AB - BACKGROUND: Cardiac troponin (cTn) levels exceeding the 99th percentile upper reference limit and a rise/fall pattern are key for diagnosing myocardial injury and infarction. Macrotroponins, formed by patient anti-cTn antibodies targeting cTn, can cause persistently elevated cTn levels without ongoing myocardial injury. The frequency and impact of macrotroponin interference on cTn 99th percentiles are unclear. This study compares sex-specific 99th percentiles for 2 cTn assays, before and after excluding macrotroponin-positive samples, focusing on the top 10% of cTn levels.METHODS: We examined 1058 plasma samples from healthy individuals previously used for Danish cTn 99th percentiles. Following International Federation of Clinical Chemistry and Laboratory Medicine educational recommendations, macrotroponin presence was assessed in the top 10% cTn samples using immunoglobulin G (IgG) depletion screening and a reference sucrose gradient, confirming macrotroponin when both methods concurred. Due to analytical dilution constraints, [the highest] 88 of 135 Siemens Atellica high-sensitivity cTnI (hs-cTnI) samples were analyzed with both methods. All 106 Roche hs-cTnT samples were negative using IgG depletion, and sucrose analysis was limited to the highest 70 samples.RESULTS: Macrotroponin was found in 76% (67/88) of Siemens samples but in none of the Roche samples (0/70). Excluding macrotroponin-affected samples lowered the Siemens 99th percentiles from 117 ng/L to 22 ng/L in men and from 37 ng/L to 9 ng/L in women. The 99th/50th percentile ratio for Siemens decreased from 12- to 29-fold to 3- to 7-fold, approaching the Roche ratios.CONCLUSIONS: Macrotroponin significantly influenced the Siemens Atellica hs-cTnI 99th percentiles, suggesting important clinical implications that warrant further prospective studies. The 99th/50th percentile ratio may help evaluate macrotroponin interference in troponin assays.
KW - Female
KW - Humans
KW - Male
KW - Middle Aged
KW - Myocardial Infarction/blood
KW - Reference Values
KW - Troponin I/blood
KW - Troponin T/blood
UR - http://www.scopus.com/inward/record.url?scp=105012448553&partnerID=8YFLogxK
U2 - 10.1093/clinchem/hvaf068
DO - 10.1093/clinchem/hvaf068
M3 - Journal article
C2 - 40492538
SN - 0009-9147
VL - 71
SP - 884
EP - 895
JO - Clinical Chemistry
JF - Clinical Chemistry
IS - 8
ER -