title: Serum levels of fetuin-A, osteoprotegerin and osteopontin in patients with coronary artery disease: effects of statin (HMGCoA-reductase inhibitor) therapy.
abstract: OBJECTIVE
  Statins (HMGCoA-reductase inhibitors) produce numerous non-lipid related, 'pleiotropic' effects. Our aim was to investigate whether simvastatin treatment affects serum levels of vascular calcification inhibitors, such as fetuin-A, osteoprotegerin (OPG) and osteopontin (OPN), in patients with coronary artery disease (CAD).
  
  
  METHODS
  A total of 98 statin-free patients with angiographically proven, newly diagnosed CAD were treated with simvastatin (20-40 mg daily) for 6 months to target a low-density lipoprotein (LDL) level <100 mg/dL (the statin group [SG]). Thirty-five age- and sex-matched healthy individuals without any chronic metabolic or cardiovascular disease at baseline served as a healthy control group (HCG). Clinical, anthropometrical and metabolic parameters and serum fetuin-A, OPG, OPN and high-sensitivity C-reactive protein (hsCRP) levels were assayed at baseline in all participants and after 6 months only in SG patients.
  
  
  RESULTS
  Compared with HCG subjects at baseline, SG patients exhibited higher serum levels of OPG (7.39 ± 2.94 pmol/L vs 2.47 ± 1.15 pmol/L, p < 0.001), OPN (60.99 ± 17.52 ng/mL vs 45.45 ± 10.26 ng/mL, p = 0.005) and hsCRP (4.66 ± 1.74 mg/L vs 1.58 ± 0.56 mg/L, p < 0.001) as well as lower serum levels of fetuin-A (0.222 ± 0.036 μg/L vs 0.839 ± 0.092 μg/L, p < 0001). Apart from significantly reducing plasma total cholesterol and LDL, simvastatin also reduced serum levels of fetuin-A (by ~62.6 %), OPG (by ~47.2 %), OPN (by ~44.6 %) and hsCRP (by ~45.3 %) (p < 0.05) in SG patients. In standard multiple regression analysis, the simvastatin-induced reduction in fetuin-A was independently associated with changes in total cholesterol (β = -0.289, p = 0.048) and LDL (β = -0.302, p = 0.032) (R (2) = 0.305, p = 0.040).
  
  
  CONCLUSIONS
  Patients with CAD showed derangements in serum levels of all vascular calcification inhibitors compared with those in healthy controls. Simvastatin treatment for 6 months significantly decreased serum fetuin-A, OPG and OPN levels, but the clinical relevance of this requires further investigation.
authors.affiliation: Department of Vascular Surgery, Medical School, University of Athens, 1 Rimini str, 15247, Athens, Greece, nikoskad@yahoo.com.
authors.forename: Nikolaos P E
authors.initials: NP
authors.lastname: Kadoglou
authors.forename: George
authors.initials: G
authors.lastname: Kottas
authors.forename: Stylianos
authors.initials: S
authors.lastname: Lampropoulos
authors.forename: Ioulia
authors.initials: I
authors.lastname: Vitta
authors.forename: Christos D
authors.initials: CD
authors.lastname: Liapis
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D003324:Coronary Artery Disease / Q000097:blood* / Q000188:drug therapy*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D053495:Osteopontin / Q000097:blood*; D053244:Osteoprotegerin / Q000097:blood*; D011446:Prospective Studies; D016896:Treatment Outcome; D060749:alpha-2-HS-Glycoprotein / Q000378:metabolism*
chemical_list: C556354:AHSG protein, human; D015415:Biomarkers; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D053244:Osteoprotegerin; C506030:TNFRSF11B protein, human; D060749:alpha-2-HS-Glycoprotein; D053495:Osteopontin