Validation of plasma biomarkers in degenerative calcific aortic stenosis

Calcific aortic stenosis (CAS) is the most common acquired valvular disorder in industrialized countries. This study investigates the correlation of different known biomarkers for CAS as a first step towards the development of a panel of biomarkers that can be used in prognostic staging.

Venous blood samples were obtained from both patients with CAS scheduled for surgery and healthy individuals. Plasma levels of fetuin-A, NT-proBNP, BNP, homocysteine and osteopontin were measured by enzyme-linked immunosorbent assay (ELISA). CAS was measured by echocardiography and was defined as an aortic valve area of less than 2.0 cm(2). Non-paired t-tests were used for comparison.

CAS was present in 33 subjects (mean age 75.9 y) and absent in 11 subjects (mean age 55.36 y). Individuals with CAS exhibited higher plasma levels of NT-proBNP (1.33 versus 0.73 pmol/mL, P < 0.05), BNP fragment (1.47 versus 0.34 ng/mL P < 0.05), and osteopontin (60.79 versus 25.42 ng/mL P < 0.05) compared with controls. Fetuin-A levels were lower in individuals with CAS than in healthy controls (0.25 versus 0.34g/L, P < 0.05). Asymmetric dimethylarginine (ADMA) were lower (1.08 versus 1.1 micromol/L, P > 0.05) while homocysteine levels (20.34 +/- 2.14 versus 19.23 +/- 4.19 P > 0.05) were higher in the CAS patients.

This study demonstrates a direct correlation of NT-pro-BNP, BNP, and osteopontin and the presence of CAS, while fetuin A showed an inverse correlation. Plasma ADMA and homocysteine levels were comparable in the CAS patients and healthy individuals. This is the first study in which several biomarkers previously studied independently in patients with CAS have been investigated simultaneously in the same study population.