Novel biomarkers associated with thoracic aortic disease

Carlijn G.E. Thijssen, Silvy Dekker, Lidia R. Bons, Laurie W. Geenen, Arjen L. Gökalp, Johanna J.M. Takkenberg, Mostafa M. Mokhles, Jos A. Bekkers, Eric Boersma, Elke Bouwens, Roland R.J. van Kimmenade, Jolien W. Roos-Hesselink*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

5 Citations (Scopus)
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Background: Biomarkers might help to improve diagnosis, surveillance and risk stratification of thoracic aortic disease (TAD). We explored the association between a broad spectrum of cardiovascular biomarkers with clinical characteristics and thoracic aortic diameter in TAD patients. Methods: Venous blood-samples were obtained in 158 clinically stable TAD patients visiting our outpatient clinic (2017–2020). TAD was defined as a thoracic aortic diameter ≥ 40 mm, or genetic confirmation (hereditary TAD). The cardiovascular panel III of the Olink multiplex platform was used for batch analysis of 92 proteins. A comparison was made between biomarker levels in patients with and without previous aortic dissection and/or surgery, and with and without hereditary TAD. Linear regression analyses were applied to identify (relative, normalized) biomarker concentrations associated with the absolute thoracic aortic diameter (ADmax), and thoracic aortic diameter indexed for body surface area (IDmax). Results: Median age of study patients was 61.0 (IQR 50.3–68.8) years, 37.3% females. Mean ADmax and IDmax were 43.3 ± 5.4 mm and 21.3 ± 3.3 mm/m2. After multivariable adjustment, Matrix Metalloproteinase-3 (MMP-3) and Insulin-like growth factor binding protein 2 (IGFBP-2) showed a significant positive association with ADmax and IDmax, respectively. Patients with previous aortic surgery/dissection had higher N-terminal-pro hormone BNP (NTproBNP) (median 3.67 [IQR 3.01–3.99] vs 2.84 [2.32–3.26], p ≤0.001). Patients with hereditary TAD had higher Trem-like transcript protein 2 (TLT-2) (median 4.64 [IQR 4.45–4.84]) than those with non-heriditary TAD (4.40 [4.17–4.64]; p = 0.00042). Conclusions: Among a broad range of biomarkers, MMP-3 and IGFBP-2 were associated with disease severity in TAD patients. The pathophysiological pathways uncovered by these biomarkers, and their potential clinical use warrants further research.

Original languageEnglish
Pages (from-to)115-122
Number of pages8
JournalInternational Journal of Cardiology
Publication statusPublished - 1 May 2023

Bibliographical note

Funding Information:
This study was supported by The Netherlands Organization for Health Research and Development ZonMW [Grant number 849200014 ].

Publisher Copyright: © 2023 The Author(s)


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