Validation of Plasma Biomarkers in Degenerative Calcific Aortic Stenosis

Ferrari, Giovanni; Sainger, Rachana; Beckmann, Erik; Keller, Gianluca; Yu, Pey-Jen; Monti, Maria Cristina; Galloway, Aubrey C.; Weiss, Richard L.; Vernick, William; Grau, Juan B.

doi:10.1016/j.jss.2010.04.010

« Previous Next »Journal of Surgical Research
Volume 163, Issue 1 , Pages 12-17, September 2010

Validation of Plasma Biomarkers in Degenerative Calcific Aortic Stenosis

Giovanni Ferrari, Ph.D.
- Department of Surgery, Division of Cardiovascular Surgery, University of Pennsylvania School of Medicine Philadelphia, Pennsylvania
- To whom correspondence and reprint requests should be addressed at Harrison Department of Surgical Research, University of Pennsylvania School of Medicine, 500 S. Ridgeway Ave, Room 257, Glenolden, PA 19036.
Rachana Sainger, Ph.D.
- Department of Surgery, Division of Cardiovascular Surgery, University of Pennsylvania School of Medicine Philadelphia, Pennsylvania
Erik Beckmann, M.D.
- Department of Surgery, Division of Cardiovascular Surgery, University of Pennsylvania School of Medicine Philadelphia, Pennsylvania
Gianluca Keller
- Department of Surgery, Division of Cardiovascular Surgery, University of Pennsylvania School of Medicine Philadelphia, Pennsylvania
Pey-Jen Yu, M.D.
- New York University School of Medicine, Department of Cardiothoracic Surgery, New York University School of Medicine New York, New York
Maria Cristina Monti, Ph.D.
- Department of Biostatistics, Columbia University, New York, New York
Aubrey C. Galloway, M.D.
- New York University School of Medicine, Department of Cardiothoracic Surgery, New York University School of Medicine New York, New York
Richard L. Weiss, M.D.
- Department of Surgery, Division of Cardiovascular Surgery, University of Pennsylvania School of Medicine Philadelphia, Pennsylvania
William Vernick, M.D.
- Department of Surgery, Division of Cardiovascular Surgery, University of Pennsylvania School of Medicine Philadelphia, Pennsylvania
Juan B. Grau, M.D.
- Department of Surgery, Division of Cardiovascular Surgery, University of Pennsylvania School of Medicine Philadelphia, Pennsylvania

Received 8 January 2010 published online 10 May 2010.

Background

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.

Methods

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 cm². Non-paired t-tests were used for comparison.

Results

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 μmol/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.

Conclusion

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.

Key Words: calcific aortic stenosis (CAS), biomarkers, heart diseases, aortic valve calcification, prevention, fetuin A, NT-proBNP, brain natriuretic peptide (BNP), osteopontin (OPN), asymmetric dimethylarginine (ADMA), homocysteine