title: Impact of statins on serial coronary calcification during atheroma progression and regression.
abstract: BACKGROUND
  Statins can regress coronary atheroma and lower clinical events. Although pre-clinical studies suggest procalcific effects of statins in vitro, it remains unclear if statins can modulate coronary atheroma calcification in vivo.
  
  
  OBJECTIVE
  This study compared changes in coronary atheroma volume and calcium indices (CaI) in patients receiving high-intensity statin therapy (HIST), low-intensity statin therapy (LIST), and no-statin therapy.
  
  
  METHODS
  In a post-hoc patient-level analysis of 8 prospective randomized trials using serial coronary intravascular ultrasound, serial changes in coronary percent atheroma volume (PAV) and CaI were measured across matched coronary segments in patients with coronary artery disease.
  
  
  RESULTS
  Following propensity-weighted adjustment for differences in baseline and changes in clinical, laboratory, and ultrasonic characteristics, HIST (n = 1,545) associated with PAV regression from baseline (-0.6 ± 0.1%; p < 0.001), whereas both LIST (n = 1,726) and no-statin therapy (n = 224) associated with PAV progression (+0.8 ± 0.1% and +1.0 ± 0.1%; p < 0.001, respectively; p < 0.001 for both HIST vs. LIST and HIST vs. no-statin; p = 0.35 for LIST vs. no-statin). Significant increases in CaI from baseline were noted across all groups (median [interquartile range] HIST, +0.044 [0.0-0.12]; LIST, +0.038 [0.0-0.11]; no-statin, +0.020 [0.0-0.10]; p < 0.001 for all), which could relate to statin intensity (p = 0.03 for LIST vs. no-statin; p = 0.007 for HIST vs. no-statin; p = 0.18 for HIST vs. LIST). No correlations were found between changes in CaI and on-treatment levels of atherogenic and antiatherogenic lipoproteins, and C-reactive protein, in either of the HIST groups or the no-statin group.
  
  
  CONCLUSIONS
  Independent of their plaque-regressive effects, statins promote coronary atheroma calcification. These findings provide insight as to how statins may stabilize plaque beyond their effects on plaque regression.
authors.affiliation: Cleveland Clinic Coordinating Center for Clinical Research (C5R), Cleveland, Ohio; Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland, Ohio.
authors.forename: Rishi
authors.initials: R
authors.lastname: Puri
authors.affiliation: South Australian Health and Medical Research Institute, University of Adelaide, Adelaide, South Australia, Australia.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Nicholls
authors.affiliation: Cleveland Clinic Coordinating Center for Clinical Research (C5R), Cleveland, Ohio.
authors.forename: Mingyuan
authors.initials: M
authors.lastname: Shao
authors.affiliation: South Australian Health and Medical Research Institute, University of Adelaide, Adelaide, South Australia, Australia.
authors.forename: Yu
authors.initials: Y
authors.lastname: Kataoka
authors.affiliation: Cleveland Clinic Coordinating Center for Clinical Research (C5R), Cleveland, Ohio.
authors.forename: Kiyoko
authors.initials: K
authors.lastname: Uno
authors.affiliation: Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland, Ohio.
authors.forename: Samir R
authors.initials: SR
authors.lastname: Kapadia
authors.affiliation: Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland, Ohio.
authors.forename: E Murat
authors.initials: EM
authors.lastname: Tuzcu
authors.affiliation: Cleveland Clinic Coordinating Center for Clinical Research (C5R), Cleveland, Ohio; Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland, Ohio. Electronic address: nissens@ccf.org.
authors.forename: Steven E
authors.initials: SE
authors.lastname: Nissen
mesh_terms: D000368:Aged; D002118:Calcium / Q000097:blood; D003324:Coronary Artery Disease / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology; D003331:Coronary Vessels / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000473:pathology; D018450:Disease Progression; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D058226:Plaque, Atherosclerotic / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology; D011446:Prospective Studies; D018084:Ultrasonography, Interventional; D061205:Vascular Calcification / Q000000981:diagnostic imaging / Q000188:drug therapy*
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D002118:Calcium
keywords: atherosclerosis; calcium; intravascular ultrasound; statins