title: Coronary Plaque Morphology and the Anti-Inflammatory Impact of Atorvastatin: A Multicenter 18F-Fluorodeoxyglucose Positron Emission Tomographic/Computed Tomographic Study.
abstract: BACKGROUND
  Nonobstructive coronary plaques manifesting high-risk morphology (HRM) associate with an increased risk of adverse clinical cardiovascular events. We sought to test the hypothesis that statins have a greater anti-inflammatory effect within coronary plaques containing HRM.
  
  
  RESULTS
  In this prospective multicenter study, 55 subjects with or at high risk for atherosclerosis underwent18F-fluorodeoxyglucose positron emission tomographic/computed tomographic imaging at baseline and after 12 weeks of treatment with atorvastatin. Coronary arterial inflammation (18F-fluorodeoxyglucose uptake, expressed as target-to-background ratio) was assessed in the left main coronary artery (LMCA). While blinded to the PET findings, contrast-enhanced computed tomographic angiography was performed to characterize the presence of HRM (defined as noncalcified or partially calcified plaques) in the LMCA. Arterial inflammation (target-to-background ratio) was higher in LMCA segments with HRM than those without HRM (mean±SEM: 1.95±0.43 versus 1.67±0.32 for LMCA with versus without HRM, respectively; P=0.04). Moreover, atorvastatin treatment for 12 weeks reduced target-to-background ratio more in LMCA segments with HRM than those without HRM (12 week-baseline Δtarget-to-background ratio [95% confidence interval]: -0.18 [-0.35 to -0.004] versus 0.09 [-0.06 to 0.26]; P=0.02). Furthermore, this relationship between coronary plaque morphology and change in LMCA inflammatory activity remained significant after adjusting for baseline low-density lipoprotein and statin dose (β=-0.27; P=0.038).
  
  
  CONCLUSIONS
  In this first study to evaluate the impact of statins on coronary inflammation, we observed that the anti-inflammatory impact of statins is substantially greater within coronary plaques that contain HRM features. These findings suggest an additional mechanism by which statins disproportionately benefit individuals with more advanced atherosclerotic disease.
  
  
  BACKGROUND
  URL: http://www.clinicaltrials.gov. Unique identifier: NCT00703261.
authors.affiliation: From the Division of Cardiology, New York Presbyterian Hospital and Weill Cornell Medical College (P.S.); Cardiac MR PET CT Program, Division of Cardiac Imaging (H.E., S.S., P.M.-H., G.M.-S., Amr Abdelbaky, U.H., A.T.) and Division of Cardiology (A.T.), Massachusetts General Hospital and Harvard Medical School, Boston; MTA-SE Cardiovascular Imaging Research Group, Semmelweis University, Budapest, Hungary (P.M.-H.); Fundacion Cardio-Infantil, Bogota, Colombia (H.M.M.); Merck and Company, Inc, Kenilworth, NJ (Achilles Alon, S.S.S.); Division of Cardiovascular Medicine, University of Cambridge, United Kingdom (J.H.F.R.); and Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY (Z.A.F.).
authors.forename: Parmanand
authors.initials: P
authors.lastname: Singh
authors.affiliation: From the Division of Cardiology, New York Presbyterian Hospital and Weill Cornell Medical College (P.S.); Cardiac MR PET CT Program, Division of Cardiac Imaging (H.E., S.S., P.M.-H., G.M.-S., Amr Abdelbaky, U.H., A.T.) and Division of Cardiology (A.T.), Massachusetts General Hospital and Harvard Medical School, Boston; MTA-SE Cardiovascular Imaging Research Group, Semmelweis University, Budapest, Hungary (P.M.-H.); Fundacion Cardio-Infantil, Bogota, Colombia (H.M.M.); Merck and Company, Inc, Kenilworth, NJ (Achilles Alon, S.S.S.); Division of Cardiovascular Medicine, University of Cambridge, United Kingdom (J.H.F.R.); and Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY (Z.A.F.).
authors.forename: Hamed
authors.initials: H
authors.lastname: Emami
authors.affiliation: From the Division of Cardiology, New York Presbyterian Hospital and Weill Cornell Medical College (P.S.); Cardiac MR PET CT Program, Division of Cardiac Imaging (H.E., S.S., P.M.-H., G.M.-S., Amr Abdelbaky, U.H., A.T.) and Division of Cardiology (A.T.), Massachusetts General Hospital and Harvard Medical School, Boston; MTA-SE Cardiovascular Imaging Research Group, Semmelweis University, Budapest, Hungary (P.M.-H.); Fundacion Cardio-Infantil, Bogota, Colombia (H.M.M.); Merck and Company, Inc, Kenilworth, NJ (Achilles Alon, S.S.S.); Division of Cardiovascular Medicine, University of Cambridge, United Kingdom (J.H.F.R.); and Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY (Z.A.F.).
authors.forename: Sharath
authors.initials: S
authors.lastname: Subramanian
authors.affiliation: From the Division of Cardiology, New York Presbyterian Hospital and Weill Cornell Medical College (P.S.); Cardiac MR PET CT Program, Division of Cardiac Imaging (H.E., S.S., P.M.-H., G.M.-S., Amr Abdelbaky, U.H., A.T.) and Division of Cardiology (A.T.), Massachusetts General Hospital and Harvard Medical School, Boston; MTA-SE Cardiovascular Imaging Research Group, Semmelweis University, Budapest, Hungary (P.M.-H.); Fundacion Cardio-Infantil, Bogota, Colombia (H.M.M.); Merck and Company, Inc, Kenilworth, NJ (Achilles Alon, S.S.S.); Division of Cardiovascular Medicine, University of Cambridge, United Kingdom (J.H.F.R.); and Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY (Z.A.F.).
authors.forename: Pal
authors.initials: P
authors.lastname: Maurovich-Horvat
authors.affiliation: From the Division of Cardiology, New York Presbyterian Hospital and Weill Cornell Medical College (P.S.); Cardiac MR PET CT Program, Division of Cardiac Imaging (H.E., S.S., P.M.-H., G.M.-S., Amr Abdelbaky, U.H., A.T.) and Division of Cardiology (A.T.), Massachusetts General Hospital and Harvard Medical School, Boston; MTA-SE Cardiovascular Imaging Research Group, Semmelweis University, Budapest, Hungary (P.M.-H.); Fundacion Cardio-Infantil, Bogota, Colombia (H.M.M.); Merck and Company, Inc, Kenilworth, NJ (Achilles Alon, S.S.S.); Division of Cardiovascular Medicine, University of Cambridge, United Kingdom (J.H.F.R.); and Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY (Z.A.F.).
authors.forename: Gergana
authors.initials: G
authors.lastname: Marincheva-Savcheva
authors.affiliation: From the Division of Cardiology, New York Presbyterian Hospital and Weill Cornell Medical College (P.S.); Cardiac MR PET CT Program, Division of Cardiac Imaging (H.E., S.S., P.M.-H., G.M.-S., Amr Abdelbaky, U.H., A.T.) and Division of Cardiology (A.T.), Massachusetts General Hospital and Harvard Medical School, Boston; MTA-SE Cardiovascular Imaging Research Group, Semmelweis University, Budapest, Hungary (P.M.-H.); Fundacion Cardio-Infantil, Bogota, Colombia (H.M.M.); Merck and Company, Inc, Kenilworth, NJ (Achilles Alon, S.S.S.); Division of Cardiovascular Medicine, University of Cambridge, United Kingdom (J.H.F.R.); and Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY (Z.A.F.).
authors.forename: Hector M
authors.initials: HM
authors.lastname: Medina
authors.affiliation: From the Division of Cardiology, New York Presbyterian Hospital and Weill Cornell Medical College (P.S.); Cardiac MR PET CT Program, Division of Cardiac Imaging (H.E., S.S., P.M.-H., G.M.-S., Amr Abdelbaky, U.H., A.T.) and Division of Cardiology (A.T.), Massachusetts General Hospital and Harvard Medical School, Boston; MTA-SE Cardiovascular Imaging Research Group, Semmelweis University, Budapest, Hungary (P.M.-H.); Fundacion Cardio-Infantil, Bogota, Colombia (H.M.M.); Merck and Company, Inc, Kenilworth, NJ (Achilles Alon, S.S.S.); Division of Cardiovascular Medicine, University of Cambridge, United Kingdom (J.H.F.R.); and Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY (Z.A.F.).
authors.forename: Amr
authors.initials: A
authors.lastname: Abdelbaky
authors.affiliation: From the Division of Cardiology, New York Presbyterian Hospital and Weill Cornell Medical College (P.S.); Cardiac MR PET CT Program, Division of Cardiac Imaging (H.E., S.S., P.M.-H., G.M.-S., Amr Abdelbaky, U.H., A.T.) and Division of Cardiology (A.T.), Massachusetts General Hospital and Harvard Medical School, Boston; MTA-SE Cardiovascular Imaging Research Group, Semmelweis University, Budapest, Hungary (P.M.-H.); Fundacion Cardio-Infantil, Bogota, Colombia (H.M.M.); Merck and Company, Inc, Kenilworth, NJ (Achilles Alon, S.S.S.); Division of Cardiovascular Medicine, University of Cambridge, United Kingdom (J.H.F.R.); and Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY (Z.A.F.).
authors.forename: Achilles
authors.initials: A
authors.lastname: Alon
authors.affiliation: From the Division of Cardiology, New York Presbyterian Hospital and Weill Cornell Medical College (P.S.); Cardiac MR PET CT Program, Division of Cardiac Imaging (H.E., S.S., P.M.-H., G.M.-S., Amr Abdelbaky, U.H., A.T.) and Division of Cardiology (A.T.), Massachusetts General Hospital and Harvard Medical School, Boston; MTA-SE Cardiovascular Imaging Research Group, Semmelweis University, Budapest, Hungary (P.M.-H.); Fundacion Cardio-Infantil, Bogota, Colombia (H.M.M.); Merck and Company, Inc, Kenilworth, NJ (Achilles Alon, S.S.S.); Division of Cardiovascular Medicine, University of Cambridge, United Kingdom (J.H.F.R.); and Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY (Z.A.F.).
authors.forename: Sudha S
authors.initials: SS
authors.lastname: Shankar
authors.affiliation: From the Division of Cardiology, New York Presbyterian Hospital and Weill Cornell Medical College (P.S.); Cardiac MR PET CT Program, Division of Cardiac Imaging (H.E., S.S., P.M.-H., G.M.-S., Amr Abdelbaky, U.H., A.T.) and Division of Cardiology (A.T.), Massachusetts General Hospital and Harvard Medical School, Boston; MTA-SE Cardiovascular Imaging Research Group, Semmelweis University, Budapest, Hungary (P.M.-H.); Fundacion Cardio-Infantil, Bogota, Colombia (H.M.M.); Merck and Company, Inc, Kenilworth, NJ (Achilles Alon, S.S.S.); Division of Cardiovascular Medicine, University of Cambridge, United Kingdom (J.H.F.R.); and Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY (Z.A.F.).
authors.forename: James H F
authors.initials: JH
authors.lastname: Rudd
authors.affiliation: From the Division of Cardiology, New York Presbyterian Hospital and Weill Cornell Medical College (P.S.); Cardiac MR PET CT Program, Division of Cardiac Imaging (H.E., S.S., P.M.-H., G.M.-S., Amr Abdelbaky, U.H., A.T.) and Division of Cardiology (A.T.), Massachusetts General Hospital and Harvard Medical School, Boston; MTA-SE Cardiovascular Imaging Research Group, Semmelweis University, Budapest, Hungary (P.M.-H.); Fundacion Cardio-Infantil, Bogota, Colombia (H.M.M.); Merck and Company, Inc, Kenilworth, NJ (Achilles Alon, S.S.S.); Division of Cardiovascular Medicine, University of Cambridge, United Kingdom (J.H.F.R.); and Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY (Z.A.F.).
authors.forename: Zahi A
authors.initials: ZA
authors.lastname: Fayad
authors.affiliation: From the Division of Cardiology, New York Presbyterian Hospital and Weill Cornell Medical College (P.S.); Cardiac MR PET CT Program, Division of Cardiac Imaging (H.E., S.S., P.M.-H., G.M.-S., Amr Abdelbaky, U.H., A.T.) and Division of Cardiology (A.T.), Massachusetts General Hospital and Harvard Medical School, Boston; MTA-SE Cardiovascular Imaging Research Group, Semmelweis University, Budapest, Hungary (P.M.-H.); Fundacion Cardio-Infantil, Bogota, Colombia (H.M.M.); Merck and Company, Inc, Kenilworth, NJ (Achilles Alon, S.S.S.); Division of Cardiovascular Medicine, University of Cambridge, United Kingdom (J.H.F.R.); and Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY (Z.A.F.).
authors.forename: Udo
authors.initials: U
authors.lastname: Hoffmann
authors.affiliation: From the Division of Cardiology, New York Presbyterian Hospital and Weill Cornell Medical College (P.S.); Cardiac MR PET CT Program, Division of Cardiac Imaging (H.E., S.S., P.M.-H., G.M.-S., Amr Abdelbaky, U.H., A.T.) and Division of Cardiology (A.T.), Massachusetts General Hospital and Harvard Medical School, Boston; MTA-SE Cardiovascular Imaging Research Group, Semmelweis University, Budapest, Hungary (P.M.-H.); Fundacion Cardio-Infantil, Bogota, Colombia (H.M.M.); Merck and Company, Inc, Kenilworth, NJ (Achilles Alon, S.S.S.); Division of Cardiovascular Medicine, University of Cambridge, United Kingdom (J.H.F.R.); and Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY (Z.A.F.). atawakol@mgh.harvard.edu.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Tawakol
mesh_terms: D000328:Adult; D000368:Aged; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D000069059:Atorvastatin / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D000072226:Computed Tomography Angiography; D017023:Coronary Angiography / Q000379:methods; D003324:Coronary Artery Disease / Q000097:blood / Q000000981:diagnostic imaging / Q000188:drug therapy*; D003331:Coronary Vessels / Q000000981:diagnostic imaging / Q000187:drug effects*; D004311:Double-Blind Method; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000008:administration & dosage*; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood; D008297:Male; D008875:Middle Aged; D058226:Plaque, Atherosclerotic; D000072078:Positron Emission Tomography Computed Tomography; D011237:Predictive Value of Tests; D011446:Prospective Studies; D019275:Radiopharmaceuticals / Q000008:administration & dosage*; D012307:Risk Factors; D012720:Severity of Illness Index; D013997:Time Factors; D016896:Treatment Outcome; D014481:United States; D061205:Vascular Calcification / Q000000981:diagnostic imaging / Q000188:drug therapy
chemical_list: D000893:Anti-Inflammatory Agents; D015415:Biomarkers; D018836:Inflammation Mediators; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18; D000069059:Atorvastatin
keywords: atherosclerosis; carotid artery; coronary artery disease; inflammation; positron emission tomography