title: Reduction of C-reactive protein is not associated with reduced cardiovascular risk and mortality in patients treated with statins. A meta-analysis of 22 randomized trials.
abstract: BACKGROUND
  The association between C-reactive protein (CRP) levels and risk of cardiovascular (CV) events has been reported in several studies. However, it is unclear whether a reduction in CRP is associated with a reduction in risk of clinical events. Therefore we sought to investigate, in a meta-regression analysis of randomized studies enrolling patients treated by statins, whether changes in CRP are associated with changes in risk of CV events or overall survival.
  
  
  METHODS
  Randomized trials enrolling patients treated by statins, reporting CRP at baseline and at end of follow-up, CV events [myocardial infarction (MI) and stroke], CV and all-cause mortality were selected.
  
  
  RESULTS
  Twenty-two trials enrolling 54,213 participants were included in the analysis. Meta-analysis showed that active treatment significantly reduced risk of all-cause death by 8%, myocardial infarction by 11%, stroke by 10.3% and the composite outcome (including CV death, MI and stroke) by 8%, whereas risks of CV mortality was not significantly reduced. Meta-regression analysis revealed that reduction in CRP levels was significantly associated only with the reduction of MI, whereas no relationship was identified between changes in CRP and risk of stroke, CV and all-cause mortality, and the composite outcome.
  
  
  CONCLUSIONS
  These findings demonstrate that statin-induced changes in CRP do not correlate with major CV events apart from the risk of MI nor with overall survival in high-risk patients. These data suggest that although CRP may be a surrogate marker for coronary risk, it should not be used for predicting the effectiveness of statin therapy.
authors.affiliation: Department of Advanced Biomedical Sciences, Federico II University, Naples, Italy; Center for Molecular Cardiology, University of Zurich, Zurich, Switzerland; Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele Pisana, Rome, Italy.
authors.forename: Gianluigi
authors.initials: G
authors.lastname: Savarese
authors.affiliation: Cardiovascular and Cell Sciences Research Institute, St. George's University of London, London, United Kingdom.
authors.forename: Giuseppe M C
authors.initials: GM
authors.lastname: Rosano
authors.affiliation: Department of Advanced Biomedical Sciences, Federico II University, Naples, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Parente
authors.affiliation: Department of Advanced Biomedical Sciences, Federico II University, Naples, Italy.
authors.forename: Carmen
authors.initials: C
authors.lastname: D'Amore
authors.affiliation: Center for Molecular Cardiology, University of Zurich, Zurich, Switzerland.
authors.forename: Martin F
authors.initials: MF
authors.lastname: Reiner
authors.affiliation: Center for Molecular Cardiology, University of Zurich, Zurich, Switzerland.
authors.forename: Giovanni G
authors.initials: GG
authors.lastname: Camici
authors.affiliation: Department of Advanced Biomedical Sciences, Federico II University, Naples, Italy.
authors.forename: Bruno
authors.initials: B
authors.lastname: Trimarco
authors.affiliation: Department of Advanced Biomedical Sciences, Federico II University, Naples, Italy. Electronic address: fpperron@unina.it.
authors.forename: Pasquale
authors.initials: P
authors.lastname: Perrone-Filardi
mesh_terms: D002097:C-Reactive Protein / Q000378:metabolism*; D002318:Cardiovascular Diseases / Q000097:blood / Q000453:epidemiology / Q000517:prevention & control; D002423:Cause of Death / Q000639:trends; D014943:Global Health; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D015994:Incidence; D016032:Randomized Controlled Trials as Topic; D012307:Risk Factors
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D002097:C-Reactive Protein
keywords: C-reactive protein; Cardiovascular events; Cardiovascular risk