Macrotroponin Complexes and Risk of Cardiovascular Events
11 affiliations
- 1British Heart Foundation Centre of Research Excellence, Institute for Neurosciences and Cardiovascular Research (M.d.B., A.J.F.T., T.F., Z.L., N.L.M.), University of Edinburgh, Edinburgh, United Kingdom.
- 2Usher Institute (M.d.B., C.L.M.S.), University of Edinburgh, Edinburgh, United Kingdom.
- 3Department of Clinical Chemistry, Sahlgrenska University Hospital, Göteborg, Sweden (O.H., M.K.).
- 4British Heart Foundation Cardiovascular Biomarker Laboratory (T.F.), University of Edinburgh, Edinburgh, United Kingdom.
- 5National Institute for Prevention and Cardiovascular Health and University of Galway School of Medicine, Galway, Ireland (J.W.M.).
- 6Division of Cardiology, Johns Hopkins School of Medicine, Johns Hopkins University, Baltimore, MD (J.W.M.).
- 7Department of Epidemiology and the Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD (J.W.M.).
- 8Department of Medical Sciences and Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden (B.L., K.M.E.).
- 9Department of Cardiology, Akershus University Hospital, Lørenskog, Norway (T.O.).
- 10K.G. Jebsen Center for Cardiac Biomarkers, University of Oslo, Oslo, Norway (T.O.).
- 11School of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow, United Kingdom (N.S., P.W.).
Abstract
BACKGROUND:: Cardiac troponin is increasingly used for cardiovascular risk prediction. While abnormal values often reflect subclinical cardiovascular disease, they can be raised due to interference, where antibodies influence the assay or clearance of troponin from the circulation by forming macrotroponin complexes. The frequency of macrotroponins and its association with future risk are unknown.
METHODS:: In a general population cohort, participants with both cardiac troponin I and T measurements available (n=19 499, median 49 [25th–75th percentile, 36–58] years of age, 58.3% women) were categorized into 3 groups: no myocardial injury (neither cardiac troponin I or T was elevated), suspected macrotroponin (either cardiac troponin was elevated and discordant with a >3-fold difference in concentration), and myocardial injury (either cardiac troponin was elevated without discordance). Macrotroponin complex formation was verified in a subset of samples (n=203) using immunoglobulin depletion and ultracentrifugation. Associations with future myocardial infarction, ischemic stroke, or cardiovascular death were evaluated using Cox proportional hazards models adjusted for known cardiovascular risk factors. The generalizability of our findings was determined through replication in a second general population cohort study.
RESULTS:: Elevated cardiac troponin I was present in 1% (193 of 19 499) of participants and elevated cardiac troponin T in 6% (1159 of 19 499). Among those, 48% and 57% were discordant, respectively. Biochemical testing attributed 92.5% of discordant troponin I and 15.4% of discordant troponin T to macrotroponin complexes. Participants with myocardial injury were at increased risk of future cardiovascular events compared with those without (cardiac troponin I: adjusted hazard ratio [HR], 2.90 [95% CI, 1.99–4.22]; cardiac troponin T: adjusted HR, 1.99 [95% CI, 1.63–2.42]), whereas those with suspected macrotroponin had similar risk as those without elevated values for suspected macrotroponin I (adjusted HR, 1.59 [95% CI, 0.94–2.70]) and T (adjusted HR, 1.27 [95% CI, 1.00–1.61]). Findings were similar in the replication cohort.
CONCLUSIONS:: Assay interference due to macrotroponin complex formation is common in individuals with elevated cardiac troponin concentrations in the general population, particularly for cardiac troponin I. This has important implications for the use of cardiac troponin testing for cardiovascular risk assessment in the general population.
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BibTeX
@article{bakker2026macrotroponin,
title = {{Macrotroponin Complexes and Risk of Cardiovascular Events}},
author = {Marie de Bakker and Alexander J.F. Thurston and Ola Hammarsten and Mareta Khachatryan and Takeshi Fujisawa and Ziwen Li and John W. McEvoy and Bertil Lindahl and Torbjørn Omland and Naveed Sattar and Cathie L.M. Sudlow and Kai M. Eggers and Paul Welsh and Nicholas L. Mills},
journal = {Circulation},
year = {2026},
month = sep,
doi = {10.1161/circulationaha.126.080483},
url = {https://doi.org/10.1161/circulationaha.126.080483},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Macrotroponin Complexes and Risk of Cardiovascular Events
AU - Marie de Bakker
AU - Alexander J.F. Thurston
AU - Ola Hammarsten
AU - Mareta Khachatryan
AU - Takeshi Fujisawa
AU - Ziwen Li
AU - John W. McEvoy
AU - Bertil Lindahl
AU - Torbjørn Omland
AU - Naveed Sattar
AU - Cathie L.M. Sudlow
AU - Kai M. Eggers
AU - Paul Welsh
AU - Nicholas L. Mills
PY - 2026
DA - 2026/09/08
JO - Circulation
DO - 10.1161/circulationaha.126.080483
UR - https://doi.org/10.1161/circulationaha.126.080483
AB - BACKGROUND:: Cardiac troponin is increasingly used for cardiovascular risk prediction. While abnormal values often reflect subclinical cardiovascular disease, they can be raised due to interference, where antibodies influence the assay or clearance of troponin from the circulation by forming macrotroponin complexes. The frequency of macrotroponins and its association with future risk are unknown. METHODS:: In a general population cohort, participants with both cardiac troponin I and T measurements available (n=19 499, median 49 [25th–75th percentile, 36–58] years of age, 58.3% women) were categorized into 3 groups: no myocardial injury (neither cardiac troponin I or T was elevated), suspected macrotroponin (either cardiac troponin was elevated and discordant with a >3-fold difference in concentration), and myocardial injury (either cardiac troponin was elevated without discordance). Macrotroponin complex formation was verified in a subset of samples (n=203) using immunoglobulin depletion and ultracentrifugation. Associations with future myocardial infarction, ischemic stroke, or cardiovascular death were evaluated using Cox proportional hazards models adjusted for known cardiovascular risk factors. The generalizability of our findings was determined through replication in a second general population cohort study. RESULTS:: Elevated cardiac troponin I was present in 1% (193 of 19 499) of participants and elevated cardiac troponin T in 6% (1159 of 19 499). Among those, 48% and 57% were discordant, respectively. Biochemical testing attributed 92.5% of discordant troponin I and 15.4% of discordant troponin T to macrotroponin complexes. Participants with myocardial injury were at increased risk of future cardiovascular events compared with those without (cardiac troponin I: adjusted hazard ratio [HR], 2.90 [95% CI, 1.99–4.22]; cardiac troponin T: adjusted HR, 1.99 [95% CI, 1.63–2.42]), whereas those with suspected macrotroponin had similar risk as those without elevated values for suspected macrotroponin I (adjusted HR, 1.59 [95% CI, 0.94–2.70]) and T (adjusted HR, 1.27 [95% CI, 1.00–1.61]). Findings were similar in the replication cohort. CONCLUSIONS:: Assay interference due to macrotroponin complex formation is common in individuals with elevated cardiac troponin concentrations in the general population, particularly for cardiac troponin I. This has important implications for the use of cardiac troponin testing for cardiovascular risk assessment in the general population.
SN - 0009-7322
SN - 1524-4539
ER -