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PLoS One. 2014 Jul 11;9(7):e101522. doi: 10.1371/journal.pone.0101522. eCollection 2014.

Extracellular matrix biomarker, fibulin-1, is closely related to NT-proBNP and soluble urokinase plasminogen activator receptor in patients with aortic valve stenosis (the SEAS study).

Author information

1
Hypertension in Africa Research Team (HART), North-West University, Potchefstroom, South Africa; The Cardiovascular and Metabolic Preventive Clinic, Department of Endocrinology, Centre for Individualized Medicine in Arterial Diseases (CIMA), Odense University Hospital, Odense, Denmark.
2
Department of Clinical Biochemistry and Pharmacology, Centre for Individualized Medicine in Arterial Diseases (CIMA), Odense University Hospital, Odense, Denmark.
3
Medical University of South Carolina, Department of Cell Biology, Charleston, South Carolina, United States of America.
4
Clinical Research Centre 136, Hvidovre Hospital, Copenhagen, Denmark.
5
Department of Cardiology, Bispebjerg Hospital, Copenhagen, Denmark.
6
Department of Cardiology, Glostrup Hospital, Copenhagen, Denmark.
7
Lund University and Heart Health Group, Malmö, Sweden.
8
Department of Medicine, Glostrup Hospital, Copenhagen, Denmark.

Abstract

BACKGROUND:

Fibulin-1, a circulating extracellular matrix glycoprotein, has been associated with arterial disease and elevated N-terminal prohormone B-type natriuretic peptide (NT-proBNP) in diabetes. Soluble urokinase plasminogen activator receptor (suPAR), a marker of inflammation, has been associated with subclinical atherosclerosis. Therefore, we aimed to explore the interplay between these biomarkers and mild to moderate aortic valve stenosis (AS).

METHODS:

In 374 patients with mild to moderate AS, we investigated the relationship of fibulin-1 with NT-proBNP, levels of suPAR and the degree of AS at baseline and after one and four years of treatment with Simvastatin 40 mg and Ezetimibe 10 mg or placebo.

RESULTS:

During treatment, fibulin-1 became more closely associated with NT-proBNP (βyear0 = 0.10, p = 0.08, βyear1 = 0.16, p = 0.005, βyear4 = 0.22, p<0.001) and suPAR (βyear0 = 0.05, p = 0.34, βyear1 = 0.16, p = 0.006, βyear4 = 0.13, p = 0.03) at the expense of the association to aortic valve area index (AVAI) (βyear0 = -0.14, p = 0.005, βyear1 = -0.08, p = 0.11, βyear4 = -0.06, p = 0.22) independently of age, gender, creatinine, and serum aspartate aminotransferase (Adj.Ryear02 = 0.19, Adj.Ryear12 = 0.22, Adj.Ryear42 = 0.27). Fibulin-1 was unrelated to aortic regurgitation, left ventricular mass, and ejection fraction. In patients with baseline AVAI<0.58 cm2/m2 (median value), fibulin-1 was more closely associated to NT-proBNP (βyear0 = 0.25, βyear1 = 0.21, βyear4 = 0.22, all p<0.01), and suPAR (βyear0 = 0.09, p = 0.26, βyear1 = 0.23, βyear4 = 0.21, both p<0.01) independently of age, gender, AST and treatment allocation.

CONCLUSIONS:

Increased levels of fibulin-1 were independently associated with higher levels of suPAR and NT-proBNP especially in patients with lower AVAI, suggesting that fibulin-1 may be an early marker of AS as well as cardiac fibrosis secondarily to elevated left ventricular hemodynamic load.

PMID:
25014213
PMCID:
PMC4094491
DOI:
10.1371/journal.pone.0101522
[Indexed for MEDLINE]
Free PMC Article
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