Abstract
BackgroundFibulin-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).MethodsIn 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.ResultsDuring 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.Ryear0 2 = 0.19, Adj.Ryear1 2 = 0.22, Adj.Ryear4 2 = 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.ConclusionsIncreased 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.
Highlights
Aortic stenosis is a slow progressing condition developing with increasing age and abnormal calcium build up in the aortic valve [1,2]
The total group was divided according to the predetermined median (0.58 cm2/m2) of the aortic valve area index (AVAI) and categorized in a group with mild ($0.58 cm2/m2) versus a group with moderate (,0.58 cm2/m2) aortic stenosis
The relative wall thickness (p = 0.002) and left ventricular (LV) mass index (p = 0.071) were more pronounced in the moderate aortic stenosis compared to the mild group
Summary
Aortic stenosis is a slow progressing condition developing with increasing age and abnormal calcium build up in the aortic valve [1,2]. Soluble urokinase plasminogen activator receptor (suPAR)) has an overlapping interaction with atherosclerotic formation [6] and stiffness related to aortic stenosis [3,4,7]. Fibulin-1, a calcium-binding extracellular matrix glycoprotein, recently received interest on its association with elastin fibres within cardiovascular tissue and fibrinogen cross-linking [9,10]. Fibulin-1 is related to the aminoterminal prohormone B-type natriuretic peptide (NT-proBNP) in type 2 diabetes [11] and African patients subjected to early vascular ageing [12]. In cardiovascular disease states subjected to extracellular matrix turnover, fibulin-1 participates in an augmenting fashion and gradually contributes to the progression of tissue remodelling. 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. We aimed to explore the interplay between these biomarkers and mild to moderate aortic valve stenosis (AS)
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