Saibal Mukhopadhyay1, Bhagya Narayan Pandit1, Ravindra K. Saran2, Kaushik Mazumdar2, Jamal Yusuf1, Harpreet S. Minhas3, Vijay Trehan1, Sanjay Tyagi1
Departments of 1Cardiology, 2Pathology and 3Cardiothoracic Surgery, G. B. Pant Hospital, New Delhi, India
Background and aim of the study: Fetuin-A is a circulating glycoprotein that inhibits ectopic calcification. The study aim was first, to assess serum fetuin-A level in patients with calcified rheumatic mitral valve disease (RMVD), and second, to demonstrate the presence of fetuin-A by immunohistochemistry (IHC) in calcified RMVD which, to date, has not been verified in other studies.
Methods: The study group comprised 68 adult patients with isolated RMVD and normal renal function. Of these patients, 34 (27 males, seven females; mean age 33.44 ± 9.0 years) had severe calcification (Wilkins calcium score 3 or 4) and 34 (25 males, nine females; mean age 30.8 ± 8.5 years) had mild calcification (Wilkins calcium score 1 or 2). A group of 32 age- and gender-matched healthy subjects (25 males, seven females; mean age 29.5 ± 4.6 years) served as controls. Baseline serum fetuin-A levels were measured using an enzyme-linked immunosorbent assay (ELISA), while Wilkins calcium scores were assessed using either transthoracic or transesophageal echocardiography. Serum levels of calcium, phosphorus and alkaline phosphatase were assessed in all subjects. Histopathological examinations of ten severely calcific rheumatic mitral valves were made and compared with 10 non-calcified rheumatic mitral valves, all
of which had undergone mitral valve replacement.
Results: Serum fetuin-A levels were significantly lower in RMVD patients than in controls (108.83 ± 7.1 versus 114.46 ± 3.32 ng/ml; p = 0.014). However, there was no significant difference in fetuin-A level between patients with severe (C3/C4) versus mild calcification (C1/C2) (108.84 ± 7.82 versus 108.82 ± 6.36 ng/ml; p = NS). No correlation of fetuin-A was seen with serum high-sensitivity C-reactive protein, calcium, phosphorus and alkaline phosphatase, or with Wilkins’ calcium score. IHC analyses revealed the presence of fetuin-A in the mesenchymal matrix and calcified area of calcific valves, while minimal to absent fetuin-A deposition was detected in the mesenchymal matrix of non-calcified mitral valves.
Conclusion: Serum fetuin-A levels were significantly decreased in patients with calcific RMVD. The present study was the first to demonstrate fetuin-A in the calcified mitral valve of rheumatic etiology, and suggests its possible role in the pathophysiology of calcific mitral valve disease. Further studies are required, however, to determine therapeutic implications.
The Journal of Heart Valve Disease 2014;23:55-65
|Systemic and Local Levels of Fetuin-A in Calcified Mitral Valves of Rheumatic Heart Disease|
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