Is It Important to Measure or Reduce C-Reactive Protein in People at Risk of Cardiovascular Disease?


Systemic and local vascular inflammation is implicated in atherogenesis, and high-sensitivity C-reactive protein (hs-CRP) assays in healthy individuals have been associated with cardiovascular (CV) events years later. Based on the JUPITER (The Justification for the Use of statins in Primary prevention: an Intervention Trial Evaluating Rosuvastatin) study, the US Food and Drug Administration approved an amended license for rosuvastatin for the primary prevention of CV disease (CVD) events in men and women over 50 and 60 years, respectively, with one other risk factor and a CRP concentration of >2 mg/L. The European Medicines Evaluation Agency (EMEA) took a more cautious view and opted to license rosuvastatin in individuals at a high risk of CVD based on the ‘established’ risk factors, but was criticized for its failure to incorporate recommending CRP measurement in the licensing decision. However, critical scrutiny of the evidence prior to the JUPITER trial reduces confidence in the role of CRP as a predictive test, therapeutic target, or to guide statin therapy. Furthermore, meta-regression and simulation analysis support the view that the relative risk reduction observed in JUPITER was within the bounds expected from the degree of low-density lipoprotein cholesterol reduction. Any residual deviation might be adequately explained by the premature termination of the trial, which is known to contribute to overestimation of treatment effects. It appears that available evidence does not provide compelling evidence for the CRP measurement for risk prediction or the targeting of statins, nor that CRP lowering is a valid therapeutic goal for the primary prevention of CVD. The lessons learned with CRP should help us in the future evaluation of other biomarkers of CVD risk.

Clinical Topics: Dyslipidemia, Nonstatins, Novel Agents, Statins

Keywords: C-Reactive Protein, Biological Markers, United States Food and Drug Administration, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Cardiovascular Diseases

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