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

doi:10.1016/j.ijcard.2023.02.006

Novel biomarkers associated with thoracic aortic disease

Int J Cardiol. 2023 May 1:378:115-122. doi: 10.1016/j.ijcard.2023.02.006. Epub 2023 Feb 14.

Affiliations

¹ Department of Cardiology, Erasmus MC, Rotterdam, the Netherlands; Department of Cardiology, Radboud University Medical Center, Nijmegen, the Netherlands.
² Department of Cardiology, Erasmus MC, Rotterdam, the Netherlands.
³ Department of Cardiothoracic Surgery, Erasmus MC, Rotterdam, the Netherlands.
⁴ Department of Cardiothoracic Surgery, Erasmus MC, Rotterdam, the Netherlands; Department of Cardiothoracic Surgery, University Medical Center Utrecht, Utrecht, the Netherlands.
⁵ Department of Cardiology, Erasmus MC, Rotterdam, the Netherlands; Department of Anesthesiology, Erasmus MC, Rotterdam, the Netherlands.
⁶ Department of Cardiology, Erasmus MC, Rotterdam, the Netherlands. Electronic address: j.roos@erasmusmc.nl.

PMID: 36796491
DOI: 10.1016/j.ijcard.2023.02.006

Abstract

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 (AD_max), and thoracic aortic diameter indexed for body surface area (ID_max).

Results: Median age of study patients was 61.0 (IQR 50.3-68.8) years, 37.3% females. Mean AD_max and ID_max 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 AD_max and ID_max, 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.

Keywords: Biomarkers; Gender; Hereditary thoracic aortic diseases; Sex; Thoracic aortic diseases.

MeSH terms

Aged
Aorta, Thoracic / diagnostic imaging
Aorta, Thoracic / metabolism
Aortic Aneurysm, Thoracic* / diagnosis
Aortic Aneurysm, Thoracic* / genetics
Aortic Diseases*
Aortic Dissection* / diagnosis
Biomarkers / metabolism
Female
Humans
Insulin-Like Growth Factor Binding Protein 2
Male
Matrix Metalloproteinase 3 / metabolism
Middle Aged

Substances

Matrix Metalloproteinase 3
Insulin-Like Growth Factor Binding Protein 2
Biomarkers