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

Christopher R deFilippi; Henry Tran; Raghav Gattani; Lori B Daniels; Palak Shah; Leonard Ilkhanoff; Robert Christenson; Joao A Lima; Stephen Seliger

doi:10.3389/fcvm.2023.1104715

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

Front Cardiovasc Med. 2023 Feb 9:10:1104715. doi: 10.3389/fcvm.2023.1104715. eCollection 2023.

Authors

Christopher R deFilippi¹, Henry Tran¹, Raghav Gattani¹, Lori B Daniels², Palak Shah¹, Leonard Ilkhanoff¹, Robert Christenson³, Joao A Lima⁴, Stephen Seliger³

Affiliations

¹ Inova Heart and Vascular Institute, Falls Church, VA, United States.
² Division of Cardiology, University of California and San Diego Medical Center, San Diego, CA, United States.
³ Department of Pathology, University of Maryland School of Medicine, Baltimore, MD, United States.
⁴ The Johns Hopkins School of Medicine, Baltimore, MD, United States.

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.

Grants and funding

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.