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. 2024 Oct 8;150(15):1187-1198.
doi: 10.1161/CIRCULATIONAHA.123.066565. Epub 2024 Sep 10.

Half-Life and Clearance of Cardiac Troponin I and Troponin T in Humans

Jonas Henrik Kristensen  1   2   3 , Rasmus Bo Hasselbalch  1   2   3 , Nina Strandkjær  1   2   3 , Nicoline Jørgensen  1   2 , Morten Østergaard  4 , Peter Hasse Møller-Sørensen  4 , Jens Christian Nilsson  4 , Shoaib Afzal  5   3 , Pia Rørbæk Kamstrup  5 , Morten Dahl  3   6 , Mustafa Vakur Bor  7 , Ruth Frikke-Schmidt  8 , Niklas Rye Jørgensen  3   8 , Line Rode  8 , Lene Holmvang  9 , Jesper Kjærgaard  3   9 , Lia Evi Bang  9 , Julie Forman  10 , Kim Dalhoff  3   11 , Allan S Jaffe  12 , Kristian Thygesen  13   14 , Henning Bundgaard #  3   9 , Kasper Karmark Iversen #  1   2   3
Affiliations

Half-Life and Clearance of Cardiac Troponin I and Troponin T in Humans

Jonas Henrik Kristensen et al. Circulation. .

Abstract

Background: Cardiac troponin (cTn) is key in diagnosing myocardial infarction (MI). After MI, the clinically observed half-life of cTn has been reported to be 7 to 20 hours, but this estimate reflects the combined elimination and simultaneous release of cTn from cardiomyocytes. More precise timing of myocardial injuries necessitates separation of these 2 components. We used a novel method for determination of isolated cTn elimination kinetics in humans.

Methods: Patients with MI were included within 24 hours after revascularization and underwent plasmapheresis to obtain plasma with a high cTn concentration. After at least 3 weeks, patients returned for an autologous plasma retransfusion followed by blood sampling for 8 hours. cTn was measured with 5 different high-sensitivity cTn assays.

Results: Of 25 included patients, 20 participants (mean age, 64.5 years; SD, 8.2 years; 4 women [20%]) received a retransfusion after a median of 5.8 weeks (interquartile range, 5.0-6.9 weeks) after MI. After retransfusion of a median of 620 mL (range, 180-679 mL) autologous plasma, the concentration of cTn in participants' blood increased 4 to 445 times above the upper reference level of the 5 high-sensitivity cTn assays. The median elimination half-life ranged from 134.1 minutes (95% CI, 117.8-168.0) for the Elecsys high-sensitivity cTnT assay to 239.7 minutes (95% CI, 153.7-295.1) for the Vitros high-sensitivity cTnI assay. The median clearance of cTnI ranged from 40.3 mL/min (95% CI, 32.0-44.9) to 52.7 mL/min (95% CI, 42.2-57.8). The clearance of cTnT was 77.0 mL/min (95% CI, 45.2-95.0).

Conclusions: This novel method showed that the elimination half-life of cTnI and cTnT was 5 to 16 hours shorter than previously reported. This indicates a considerably longer duration of cardiomyocyte cTn release after MI than previously thought. Improved knowledge of timing of myocardial injury may call for changes in the management of MI and other disorders with myocardial injury.

Keywords: biomarkers; myocardial infarction; pharmacokinetics; troponin.

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Conflict of interest statement

Dr Bundgaard received payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing, or educational events from Amgen, Sanofi, BMS, and MSD. Dr Bundgaard owns stock or stock options in Novo Nordic. Dr Kamstrup reported a grant from Gangsted Fonden outside the present work. P.R.K. reported consulting fees from Novartis and Silence Therapeutics. Dr Kamstrup reported payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing, or educational events from Physicians’ Academy for Cardiovascular Education, Novartis, and PCSK9 Forum. Dr Frikke-Schmidt reported grants or contracts outside the present work from Lundbeck Foundation, The Danish Heart Foundation, and Sygeforsikringen Denmark Research Fund. Dr Kjærgaard reports a grant or contract from Novo Nordisk Foundation outside the present work. Dr Holmvang reported personal payment or honoraria for lectures from Boehringer Ingelheim and payment or honoraria to her institution for lectures from Bayer. Dr Holmvang reported receiving support for travel from Abbott to her institution. Dr Bor reported receiving honoraria for a lecture from Bristol-Myers. Dr Thygesen reported participation on the Data Safety Monitoring Board of DANBLOCK (Danish Trial of Beta Blocker Treatment After Myocardial Infarction Without Reduced Ejection Fraction) and REDUCE (Randomized Evaluation of Decreased Usage of Betablockers After Myocardial Infarction in the SWEDEHEART Registry). Dr Jaffe reported royalties or licenses and stock or stock options to RCE Technologies; consulting fees from Abbott, Roche, Beckman-Coulter, Radiometer, Siemens, Ortho Diagnostics, Spinship, and LuminaRx; and support for attending meetings and/or travel from the American Association for Clinical Chemistry. Dr Dahl reporting receiving payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing, or educational events from Grifols and Ciesi to himself and support for attending ERS Congress 2022 from Grifols.

Figures

Figure 1.
Figure 1.
Study course steps. Step 1: Patients were admitted and treated by percutaneous coronary intervention resulting from ST-segment–elevation myocardial infarction. Step 2: Hospital charts were checked for patients eligible for participation. Step 3: Consent was obtained. Step 4: A dialysis catheter was inserted into one of the femoral veins. Step 5: Plasmapheresis was performed, and plasma was immediately frozen. Step 6: Participants finished hospitalized treatment and were discharged. Step 7: Three to 17 weeks later, participants were readmitted to perform autologous plasma transfusion. Step 8: Blood samples were collected at fixed time points from retransfusion to 8 hours later. Created with BioRender.com.
Figure 2.
Figure 2.
Flowchart of study inclusion and completion. Patients who had been examined by coronary angiography within 24 hours were screened for eligibility. Some eligible patients were not asked to participate because of capacity limitations, as only one participant could be included each day. cTnT indicates cardiac troponin T.
Figure 3.
Figure 3.
Decay of cTnI and cTnT over time. Decay of cardiac troponin (cTn) visualized by concentration from the end of retransfusion to 8 hours after measured by 5 high-sensitivity (hs) cTn assay. Scatterplots represent individual measurements for each participant. The exponential 2-phase model is plotted as curves for each participant. Participant 10 is marked by dark red; ◊ indicates the only participant with known chronic kidney disease. cTnI indicates cardiac troponin I; and Conc., concentration.
Figure 4.
Figure 4.
Comparison of elimination kinetics across cTn assays. Comparison of elimination kinetics across cardiac troponin (cTn) assays. A, Median distribution half-life of cTn according to high-sensitivity (hs) cardiac troponin I (cTnI) and hs–cardiac troponin I (cTnT) assays with 95% CIs. B, Median elimination half-life of cTns according to hs-cTnI and hs-cTnT assays with 95% CIs. C, Median clearance of cTns by hs-cTnI and hs-cTnT assays with 95% CI. D, Median distribution volume of cTns according to hs-cTnI and hs-cTnT assays with 95% CIs.
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