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)

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Peer-Reviewed Research
  • SDG 3
  • 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 ofsuPAR 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 (byear0= 0.10, p = 0.08, byear1= 0.16, p = 0.005, byear4= 0.22, p,0.001) and suPAR (byear0= 0.05, p = 0.34, byear1= 0.16, p = 0.006, byear4 = 0.13, p = 0.03) at the expense of the association to aortic valve area index (AVAI) (byear0=20.14, p = 0.005, byear1=20.08, p = 0.11, byear4=20.06, p = 0.22) independently of age, gender, creatinine, and serum aspartate aminotransferase (Adj.R year02= 0.19, Adj.R year12= 0.22, Adj.R year42= 0.27). Fibulin-1 was unrelated to aortic regurgitation, left ventricular mass, and ejection fraction. In patients with baseline AVAI, 0.58 cm 2/m2(median value), fibulin-1 was more closely associated to NT-proBNP(byear0= 0.25, byear1= 0.21, byear4= .22, all p, 0.01), and suPAR (byear0= 0.09, p = 0.26, byear1 = 0.23, byear4= 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