title: A multimarker study of degenerative aortic valve disease: stenoinsufficiency shows more indices of bad prognosis.
abstract: OBJECTIVE
  It was the aim of this study to assess the pathophysiological, prognostic role of aortic regurgitation (AR) in the 'mixed pictures' of degenerative aortic valve stenoinsufficiency (ASI) by a multimarker clinical approach.
  
  
  METHODS
  We enrolled 112 consecutive surgical
  
  
  METHODS
  19 with pure valve stenosis (PAS), 39 with mild regurgitation, 29 with severe regurgitation, and 25 controls with annulo-ectatic AR. All underwent complete echocardiography, carotid ultrasound and aortic/coronary multislice computed tomography calcium score evaluation. We determined tissue semiquantitative osteopontin, metalloproteinases (MMPs), tissue inhibitors of MMPs (TIMPs) and circulating brain natriuretic peptide. We evaluated major adverse cardiac events and cardiovascular early, long-term mortality after bioprosthetic valve implantation.
  
  
  RESULTS
  Tissue calcification, carotid and coronary atherosclerotic disease were prevalent in PAS versus ASI and AR patients. The multislice computed tomography calcium score (Agatston) was comparable between PAS and ASI (PAS 3,507.3 + 2,442.6; mild AR 4,270.7 + 2,213.5; severe AR 3,568.5 + 1,823.4), but much lower in AR (1,247.8 + 2,708.6). In ASI, a plasma/tissue 'profibrotic' MMP/TIMP balance prevailed, with circulating and echocardiographic indices of myocardial dysfunction. Percentages of major adverse cardiac events and early, long-term mortality were higher in ASI.
  
  
  CONCLUSIONS
  In ASI, different, still unknown, genetic and dysplastic factors could work synergically with cardiovascular risk factors, determining a much more adverse myocardial and valve remodeling, resulting in worse clinical outcome.
authors: Department of Human Morphology and Applied Biology, University of Pisa, Pisa, Italy.
authors: Annamaria
authors: A
authors: Vianello
authors: Stefano
authors: S
authors: Perlini
authors: Stefania
authors: S
authors: Cappelli
authors: Giuseppina
authors: G
authors: Palladini
authors: Maria Carmela
authors: MC
authors: Epistolato
authors: Daniele
authors: D
authors: Della Latta
authors: Alfredo
authors: A
authors: Cerillo
authors: Sergio
authors: S
authors: Berti
authors: Dante
authors: D
authors: Chiappino
authors: Piero
authors: P
authors: Tanganelli
authors: Mattia
authors: M
authors: Glauber
authors: Annamaria
authors: A
authors: Mazzone
mesh_terms: D000368:Aged; D001022:Aortic Valve Insufficiency / Q000401:mortality* / Q000473:pathology / Q000601:surgery; D001024:Aortic Valve Stenosis / Q000401:mortality* / Q000473:pathology; D050197:Atherosclerosis / Q000401:mortality / Q000473:pathology; D015415:Biomarkers / Q000378:metabolism*; D001705:Bioprosthesis / Q000009:adverse effects; D016893:Carotid Stenosis / Q000401:mortality / Q000473:pathology; D016022:Case-Control Studies; D005260:Female; D019918:Heart Valve Prosthesis Implantation / Q000009:adverse effects; D006801:Humans; D008297:Male; D045726:Metalloproteases / Q000378:metabolism; D020097:Natriuretic Peptide, Brain / Q000378:metabolism; D053495:Osteopontin / Q000378:metabolism; D011379:Prognosis; D011446:Prospective Studies; D019714:Tissue Inhibitor of Metalloproteinases / Q000378:metabolism; D061205:Vascular Calcification / Q000401:mortality / Q000473:pathology
chemical_list: D015415:Biomarkers; D019714:Tissue Inhibitor of Metalloproteinases; D053495:Osteopontin; D020097:Natriuretic Peptide, Brain; D045726:Metalloproteases