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)
Research output: Contribution to journal › Journal article › Research › peer-review
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.
Original language | English |
---|---|
Article number | e101522 |
Journal | PloS one |
Volume | 9 |
Issue number | 7 |
Pages (from-to) | 1-8 |
Number of pages | 8 |
ISSN | 1932-6203 |
DOIs | |
Publication status | Published - 2014 |
- Aged, Aortic Valve Stenosis, Biological Markers, Calcium-Binding Proteins, Echocardiography, Extracellular Matrix, Female, Hemodynamics, Humans, Male, Middle Aged, Natriuretic Peptide, Brain, Peptide Fragments, Prospective Studies, Receptors, Urokinase Plasminogen Activator
Research areas
ID: 138134336