TY - JOUR
T1 - Biomarkers Associated With Aortic Valve Calcification
T2 - Should We Focus on Sex Specific Processes?
AU - Peeters, Frederique E. C. M.
AU - Dudink, Elton A. M. P.
AU - Weijs, Bob
AU - Fabritz, Larissa
AU - Chua, Winnie
AU - Kietselaer, Bas L. J. H.
AU - Wildberger, Joachim E.
AU - Meex, Steven J. R.
AU - Kirchhof, Paulus
AU - Crijns, Harry J. G. M.
AU - Schurgers, Leon J.
N1 - Funding Information:
Funding. We acknowledge the support from Stichting De Weijerhorst (Maastricht, Netherlands) to SM, JW, and FP, the Netherlands Cardiovascular Research Initiative: an initiative with support of the Dutch Heart Foundation, CVON 2014-9: Reappraisal of Atrial Fibrillation: interaction between hyperCoagulability, Electrical remodeling, and Vascular destabilization in the progression of AF (RACE V) to HC, the European Union’s Horizon 2020 Research and Innovation Program (CATCH ME; Grant No. 633196) to LF, PK, and HC, the British Heart Foundation (FS/13/43/30324) to LF and PK, and the Leducq Foundation to PK. Funders had no role in the design and conduct of the study.
Publisher Copyright:
© Copyright © 2020 Peeters, Dudink, Weijs, Fabritz, Chua, Kietselaer, Wildberger, Meex, Kirchhof, Crijns and Schurgers.
PY - 2020/7/10
Y1 - 2020/7/10
N2 - Objective Circulating biomarkers are useful in detection and monitoring of cardiovascular diseases. However, their role in aortic valve disease is unclear. Mechanisms are rapidly elucidated and sex differences are suggested to be involved. Therefore, we sought to identify biomarkers involved in aortic valve calcification (AVC) stratified by sex. Methods Blood samples of 34 patients with AVC (without further overt cardiovascular disease, including absence of hemodynamic consequences of valvular calcification) were compared with 136 patients without AVC. AVC was determined using computed tomography calcium scoring. Circulating biomarkers were quantified using a novel antibody-based method (Olink Proseek Multiplex Cardiovascular Panel I) and 92 biomarkers were compared between patients with and without AVC. Results In the overall population, Interleukin-1 Receptor Antagonist and pappalysin-1 were associated with increased and decreased odds of having AVC. These differences were driven by the male population [IL1RA: OR 2.79 (1.16-6.70),p= 0.022; PAPPA: OR 0.30 (0.11-0.84),p= 0.021]. Furthermore, TNF-related activation-induced cytokine (TRANCE) and fibroblast growth factor-23 were associated decreased odds of having AVC, and monocyte chemotactic protein-1 was associated with increased odds of having AVC [TRANCE: OR 0.32 (0.12-0.80),p= 0.015; FGF23: OR 0.41 (0.170-0.991),p= 0.048; MCP1: OR 2.64 (1.02-6.81),p= 0.045]. In contrast, galanin peptides and ST2 were associated with increased odds of having AVC in females [GAL: OR 12.38 (1.31-116.7),p= 0.028; ST2: OR13.64 (1.21-153.33),p= 0.034]. Conclusion In this exploratory study, we identified biomarkers involved in inflammation, fibrosis and calcification which may be associated with having AVC. Biomarkers involved in fibrosis may show higher expression in females, whilst biomarkers involved in inflammation and calcification could associate with AVC in males.
AB - Objective Circulating biomarkers are useful in detection and monitoring of cardiovascular diseases. However, their role in aortic valve disease is unclear. Mechanisms are rapidly elucidated and sex differences are suggested to be involved. Therefore, we sought to identify biomarkers involved in aortic valve calcification (AVC) stratified by sex. Methods Blood samples of 34 patients with AVC (without further overt cardiovascular disease, including absence of hemodynamic consequences of valvular calcification) were compared with 136 patients without AVC. AVC was determined using computed tomography calcium scoring. Circulating biomarkers were quantified using a novel antibody-based method (Olink Proseek Multiplex Cardiovascular Panel I) and 92 biomarkers were compared between patients with and without AVC. Results In the overall population, Interleukin-1 Receptor Antagonist and pappalysin-1 were associated with increased and decreased odds of having AVC. These differences were driven by the male population [IL1RA: OR 2.79 (1.16-6.70),p= 0.022; PAPPA: OR 0.30 (0.11-0.84),p= 0.021]. Furthermore, TNF-related activation-induced cytokine (TRANCE) and fibroblast growth factor-23 were associated decreased odds of having AVC, and monocyte chemotactic protein-1 was associated with increased odds of having AVC [TRANCE: OR 0.32 (0.12-0.80),p= 0.015; FGF23: OR 0.41 (0.170-0.991),p= 0.048; MCP1: OR 2.64 (1.02-6.81),p= 0.045]. In contrast, galanin peptides and ST2 were associated with increased odds of having AVC in females [GAL: OR 12.38 (1.31-116.7),p= 0.028; ST2: OR13.64 (1.21-153.33),p= 0.034]. Conclusion In this exploratory study, we identified biomarkers involved in inflammation, fibrosis and calcification which may be associated with having AVC. Biomarkers involved in fibrosis may show higher expression in females, whilst biomarkers involved in inflammation and calcification could associate with AVC in males.
KW - aortic valve calcification
KW - biomarkers
KW - sex-specific
KW - fibrosis
KW - inflammation
KW - STENOSIS
KW - DISEASE
KW - PROGRESSION
KW - DETERMINANTS
KW - METAANALYSIS
KW - PREVALENCE
KW - OUTCOMES
KW - IMPACT
KW - BLOOD
KW - HEART
U2 - 10.3389/fcell.2020.00604
DO - 10.3389/fcell.2020.00604
M3 - Article
C2 - 32754594
SN - 2296-634X
VL - 8
JO - Frontiers in Cell and Developmental Biology
JF - Frontiers in Cell and Developmental Biology
M1 - 604
ER -