title: Features of vulnerable plaques and clinical outcome of UA/NSTEMI: Relationship with matrix metalloproteinase functional polymorphisms.
abstract: OBJECTIVE
  To assess the association of matrix metalloproteinases (MMP) genetic polymorphism (PM) with plaques vulnerability and clinical outcome of acute vascular events.
  
  
  METHODS
  MMP-1 (-1607 G in/del), MMP-3 (-1171 A in/del), and MMP-9 microsatellite ((13-26) CA repeats around -90) PMs have been determined (i) in 204 patients with cerebrovascular disease to assess the association with features of vulnerability in carotid plaques and prevalence of stroke, (ii) in 208 patients with UA/NSTEMI to assess the association with in-hospital clinical outcome.
  
  
  RESULTS
  Plaques from carriers of MMP-1 G insertion showed significantly smaller plaques and thicker fibrous cap. In CVD patients carrying such variant, Odds Ratio for previous stroke was 0.27 (95%C.I. 0.13-0.56, P=0.0002) and, in UA/NSTEMI patients, the risk of Major Adverse Cardiac Events (MACE, persistent angina, NSTEMI, and vascular death) was 0.22 (95%C.I. 0.11-0.44, P<0.0001). No variants in MMP-3 PM were associated to differences in either plaque features or clinical outcome. Carriers of MMP-9≥22 repeats in the microsatellite had larger plaques and lipid core. In CVD patients with such variant, Odds Ratio for stroke was 2.2 (95%C.I. 1.1-4.4) and, in UA/NSTEMI patients, MACE risk was 4.1 (95%C.I. 2.3-7.4, P<0.0001). Persistent angina and NSTEMI separately provided comparable results.
  
  
  CONCLUSIONS
  Carriers of MMP-1 G insertion show smaller and more stable plaques, as well as better prognosis in acute vascular events, while patients with ≥22 repeats in MMP-9 have larger necrotic core and worse prognosis in UA/NSTEMI.
authors.affiliation: U.C.O. Clinica Medica Generale e Terapia Medica, Dipartimento di Scienze Mediche Tecnologiche e Traslazionali, Università degli Studi di Trieste, Trieste, Italy. fiotti@units.it
authors.forename: Nicola
authors.initials: N
authors.lastname: Fiotti
authors.forename: Michèle Emilia
authors.initials: ME
authors.lastname: Moretti
authors.forename: Rossana
authors.initials: R
authors.lastname: Bussani
authors.forename: Nicola
authors.initials: N
authors.lastname: Altamura
authors.forename: Francesca
authors.initials: F
authors.lastname: Zamolo
authors.forename: Riccardo
authors.initials: R
authors.lastname: Gerloni
authors.forename: Laura
authors.initials: L
authors.lastname: Ukovich
authors.forename: Elisa
authors.initials: E
authors.lastname: Ober
authors.forename: Furio
authors.initials: F
authors.lastname: Silvestri
authors.forename: Gabriele
authors.initials: G
authors.lastname: Grassi
authors.forename: Roberto
authors.initials: R
authors.lastname: Adovasio
authors.forename: Carlo
authors.initials: C
authors.lastname: Giansante
mesh_terms: D000368:Aged; D000789:Angina, Unstable / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000235:genetics*; D019278:Matrix Metalloproteinase 3 / Q000235:genetics*; D020780:Matrix Metalloproteinase 9 / Q000235:genetics*; D008875:Middle Aged; D009203:Myocardial Infarction / Q000235:genetics*; D058226:Plaque, Atherosclerotic / Q000235:genetics* / Q000473:pathology; D011110:Polymorphism, Genetic; D020521:Stroke / Q000235:genetics* / Q000473:pathology
chemical_list: D019278:Matrix Metalloproteinase 3; D020780:Matrix Metalloproteinase 9; D020781:Matrix Metalloproteinase 1