@article{9df0555a4f674088b04e031663c40376,
title = "Association of cardiac troponin T and growth differentiation factor 15 with replacement and interstitial cardiac fibrosis in community dwelling adults: The multi-ethnic study of atherosclerosis",
abstract = "Background: Subclinical abnormalities in myocardial structure (stage B heart failure) may be identified by cardiac and non-organ specific biomarkers. The associations of high-sensitivity cardiac troponin T (hs-cTnT) and growth differentiation factor-15 (GDF-15) with cardiac magnetic resonance imaging (CMR) interstitial fibrosis (extracellular volume [ECV]) is unknown and for GDF-15 the association with replacement (late gadolinium enhancement [LGE]) is also unknown. GDF-15 is a systemic biomarker also released by myocytes associated with fibrosis and inflammation. We sought to define the associations of hs-cTnT and GDF-15 with these CMR fibrosis measures in the MESA cohort. Methods: We measured hs-cTnT and GDF-15 in MESA participants free of cardiovascular disease at exam 5. CMR measurements were complete in 1737 for LGE and 1258 for ECV assessment. We estimated the association of each biomarker with LGE and increased ECV (4th quartile) using logistic regression, adjusted for demographics and risk factors. Results: Mean age of the participants was 68 ± 9 years. Unadjusted, both biomarkers were associated with LGE, but after adjustment only hs-cTnT concentrations remained significant (4th vs. 1st quartile OR] 7.5, 95% CI: 2.1, 26.6). For interstitial fibrosis both biomarkers were associated with 4th quartile ECV, but the association was attenuated compared to replacement fibrosis. After adjustment, only hs-cTnT concentrations remained significant (1st to 4th quartile OR 1.7, 95%CI: 1.1, 2.8). Conclusion: Our findings identify that both interstitial and replacement fibrosis are associated with myocyte cell death/injury, but GDF-15 a non-organ specific biomarker prognostic for incident cardiovascular disease is not associated with preclinical evidence of cardiac fibrosis.",
keywords = "GDF-15, biomarkers, cardiac disease, fibrosis, heart failure, troponin",
author = "deFilippi, {Christopher R.} and Henry Tran and Raghav Gattani and Daniels, {Lori B.} and Palak Shah and Leonard Ilkhanoff and Robert Christenson and Lima, {Joao A.} and Stephen Seliger",
note = "Funding Information: This research was supported by contracts 75N92020D00001, HHSN268201500003I, N01-HC-95159, 75N92020D00005, N01-HC-95160, 75N92020D00002, N01-HC-95161, 75N92020D00003, N01-HC-95162, 75N92020D00006, N01-HC-95163, 75N92020D00004, N01-HC-95164, 75N92020D00007, N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168, and N01-HC-95169 from the National Heart, Lung, and Blood Institute, and by grants UL1-TR-000040, UL1-TR-001079, and UL1-TR-001420 from the National Center for Advancing Translational Sciences (NCATS). This work was also supported by Roche Diagnostics, Indianapolis, IN, as an investigator-initiated grant to CdF, through the Inova Heart and Vascular Institute. The sponsor provided both funding and reagents (hs-cTnT and GDF-15) for this manuscript. Roche Diagnostics was not involved in the study design, collection, analysis, interpretation of data, the writing of this article, or the decision to submit it for publication. Funding Information: CdF received research funding to Inova from Abbott Diagnostics, Fujirebio, Ortho Clinical Diagnostics, Quidel, Roche Diagnostics, and Siemens Healthineers; independent of Inova he consults for Fujirebio, Ortho Diagnostics, Quidel, Roche Diagnostics, and Siemens Healthineers. CdF also receives unrelated research funding from the NIH R01HL154768, R01HL151293, R21AG072095, and 1UL1TR003015. RC received research funding to the University of Maryland from Roche Diagnostics, Siemens Healthineers, Becton Dickinson, Abbott, Beckman Coulter, and PixCell Medical; consulting/honoraria for Roche Diagnostics, Siemens Healthineers, Becton Dickinson, Beckman Coulter, SphingoTec, and PixCell Medical. LD was consulting for Quidel, Roche, and Siemens; has served on clinical endpoint adjudication committees for Abbott, Applied Therapeutics, Quidel, and Siemens. SS received research funding to the University of Maryland funding from Roche Diagnostics. SS, RC, and CdF were co-owners on a patent awarded to the University of Maryland (US Patent Application Number: 15/309,754) entitled: “Methods for Assessing Differential Risk for Developing Heart Failure”. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Funding Information: This research was supported by contracts 75N92020D00001, HHSN268201500003I, N01-HC-95159, 75N92020D00005, N01-HC-95160, 75N92020D00002, N01-HC-95161, 75N92020D00003, N01-HC-95162, 75N92020D00006, N01-HC-95163, 75N92020D00004, N01-HC-95164, 75N92020D00007, N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168, and N01-HC-95169 from the National Heart, Lung, and Blood Institute, and by grants UL1-TR-000040, UL1-TR-001079, and UL1-TR-001420 from the National Center for Advancing Translational Sciences (NCATS). This work was also supported by Roche Diagnostics, Indianapolis, IN, as an investigator-initiated grant to CdF, through the Inova Heart and Vascular Institute. The sponsor provided both funding and reagents (hs-cTnT and GDF-15) for this manuscript. Roche Diagnostics was not involved in the study design, collection, analysis, interpretation of data, the writing of this article, or the decision to submit it for publication. Publisher Copyright: Copyright {\textcopyright} 2023 deFilippi, Tran, Gattani, Daniels, Shah, Ilkhanoff, Christenson, Lima and Seliger.",
year = "2023",
month = feb,
day = "9",
doi = "10.3389/fcvm.2023.1104715",
language = "English (US)",
volume = "10",
journal = "Frontiers in Cardiovascular Medicine",
issn = "2297-055X",
publisher = "Frontiers Media S. A.",
}