title: C-reactive protein, but not low-density lipoprotein cholesterol levels, associate with coronary atheroma regression and cardiovascular events after maximally intensive statin therapy.
abstract: BACKGROUND
  Baseline C-reactive protein (CRP) levels predict major adverse cardiovascular events (MACE: death, myocardial infarction, stroke, coronary revascularization, and hospitalization for unstable angina). The association between changes in CRP levels with plaque progression and MACE in the setting of maximally intensive statin therapy is unknown.
  
  
  RESULTS
  The Study of Coronary Atheroma by Intravascular Ultrasound: Effect of Rosuvastatin Versus Atorvastatin (SATURN) used serial intravascular ultrasound measures of coronary atheroma volume in patients treated with rosuvastatin 40 mg or atorvastatin 80 mg for 24 months. The treatment groups did not differ significantly in the change from baseline of percent atheroma volume on intravascular ultrasound, CRP-modulating effects, or MACE rates, thus allowing for a (prespecified) post hoc analysis to test associations between the changes in CRP levels with coronary disease progression and MACE. Patients with nonincreasing CRP levels (n=621) had higher baseline (2.3 [1.1-4.7] versus 1.1 [0.5-1.8] mg/L; P<0.001) and lower follow-up CRP levels (0.8 [0.5-1.7] versus 1.6 [0.7-4.1] mg/L; P<0.001) versus those with increasing CRP levels (n=364). Multivariable analysis revealed a nonincreasing CRP level to independently associate with greater percent atheroma volume regression (P=0.01). Although the (log) change in CRP did not associate with MACE (hazard ratio, 1.18; 95% confidence interval, 0.93-1.50; P=0.17), the (log) on-treatment CRP associated significantly with MACE (hazard ratio, 1.28; 95% confidence interval, 1.04-1.56; P=0.02). On-treatment low-density lipoprotein cholesterol levels did not correlate with MACE (hazard ratio, 1.09; 95% confidence interval, 0.88-1.35; P=0.45).
  
  
  CONCLUSIONS
  Following 24 months of potent statin therapy, on-treatment CRP levels associated with MACE. Inflammation may be an important driver of residual cardiovascular risk in patients with coronary artery disease despite aggressive statin therapy.
  
  
  BACKGROUND
  http://clinicaltrials.gov. Unique identifier: NCT000620542.
authors.affiliation: Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland, OH (R.P., S.E.N., K.U., Y.K., S.J.N.); Cardiovascular Division, Brigham and Women's Hospital, Boston, MA (P.L.); C5Research, Cleveland Clinic, Cleveland, OH (M.S.); Section of Cardiovascular Research, Baylor College of Medicine, and the Methodist DeBakey Heart and Vascular Center, Houston, TX (C.M.B.); Centre for Vascular Research, University of New South Wales, Sydney, Australia (P.J.B.); INSERM Dyslipidaemia and Atherosclerosis Research Unit, Hôpital de la Pitié, Paris, France (M.J.C.); West German Heart Center, Essen, Germany (R.E.); AstraZeneca, Wilmington, DE (J.S.R.); and South Australian Health and Medical Research Institute, University of Adelaide, Adelaide, Australia (S.J.N.).
authors.forename: Rishi
authors.initials: R
authors.lastname: Puri
authors.forename: Steven E
authors.initials: SE
authors.lastname: Nissen
authors.forename: Peter
authors.initials: P
authors.lastname: Libby
authors.forename: Mingyuan
authors.initials: M
authors.lastname: Shao
authors.forename: Christie M
authors.initials: CM
authors.lastname: Ballantyne
authors.forename: Phillip J
authors.initials: PJ
authors.lastname: Barter
authors.forename: M John
authors.initials: MJ
authors.lastname: Chapman
authors.forename: Raimund
authors.initials: R
authors.lastname: Erbel
authors.forename: Joel S
authors.initials: JS
authors.lastname: Raichlen
authors.forename: Kiyoko
authors.initials: K
authors.lastname: Uno
authors.forename: Yu
authors.initials: Y
authors.lastname: Kataoka
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Nicholls
mesh_terms: D000368:Aged; D000069059:Atorvastatin; D002097:C-Reactive Protein / Q000378:metabolism*; D008078:Cholesterol, LDL / Q000378:metabolism*; D003324:Coronary Artery Disease / Q000188:drug therapy / Q000378:metabolism / Q000401:mortality; D005260:Female; D005464:Fluorobenzenes / Q000008:administration & dosage*; D005500:Follow-Up Studies; D006538:Heptanoic Acids / Q000008:administration & dosage*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage; D053208:Kaplan-Meier Estimate; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016016:Proportional Hazards Models; D011743:Pyrimidines / Q000008:administration & dosage*; D011758:Pyrroles / Q000008:administration & dosage*; D000068718:Rosuvastatin Calcium; D013449:Sulfonamides / Q000008:administration & dosage*
chemical_list: D008078:Cholesterol, LDL; D005464:Fluorobenzenes; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008077:Lipoproteins, LDL; D011743:Pyrimidines; D011758:Pyrroles; D013449:Sulfonamides; D000068718:Rosuvastatin Calcium; D002097:C-Reactive Protein; D000069059:Atorvastatin
keywords: C-reactive protein; atherosclerosis; atorvastatin; cholesterol, LDL; inflammation; rosuvastatin; ultrasonography