Tools for Practice

#1 CRP = CV?: Should We React to C-Reactive Protein?

Is high-sensitivity C-reactive protein (hs-CRP) useful in guiding the management cardiovascular (CV) disease primary prevention?

hs-CRP is not useful at identifying patients at risk of a CV event or those who may benefit from primary prevention interventions.

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JUPITER1 is used by some to justify hs-CRP testing to guide intervention for primary prevention of CV disease: 
  • Randomized controlled trial (RCT) (~90,000 screened17,802 includedwith LDL <3.4 mmol/L and hs-CRP ≥2 mg/L followed for median 1.9 years. 
    • CV events: Rosuvastatin 1.6% vs. placebo 2.8%, Number Needed to Treat (NNT)=82. 
    • All-cause mortality: Rosuvastatin 2.2% vs. placebo 2.8%, NNT=182. 
    • Several limitations:2 
      • Early study termination (which tends to exaggerate benefits3). 
      • Poor generalizability due to strict eligibility criteria. 
      • Sponsorship bias. 
      • Incomplete outcome reporting.
NRCT exists where patients are randomized to hs-CRP testing or no testing to guide therapy initiation     Context:  
  • Meta-analysis4 of 52 prospective studies (246,669 patients) found that adding hs-CRP to traditional CV risk factors (i.e. Framingham calculatordid not better identify those at risk of CV events. 
  • JUPITER added virtually nothing to statin management in primary prevention: 
    • Statins reduce CV events by relative ~25-30% across the population5 (regardless of hs-CRP6)and absolute benefit depends on patient’s individual CV risk.5 
    • Mean CRP in JUPITER would change risk obtained from Framingham calculator by only ~1-3%, which has little/no effect on treatment benefits and therefore should not influence decisions.7 
      • Example: Statin therapy reduces absolute risk by 4.5% (if baseline risk=18%) vs. 5.25% (if baseline risk=21%). 
  • hs-CRP varies widely from one measurement to the next,8,9 meaning single measurements are insufficient for decision-making. 
  • Reductions in hs-CRP are not consistently predictive of improved outcomes. 
    • Vitamin A, rosiglitazone and rofecoxib reduced hs-CRP, but worsen clinical outcomes.7 
  • Updated Canadian dyslipidemia guidelines no longer recommend routine use of hs-CRP to stratify patients, including those at “intermediate risk.10 
  Last Reviewed: July 13, 2016 by Ricky D Turgeon BSc(Pharm) ACPR PharmD 

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  • G. Michael Allan MD CCFP

1. Ridker PM, Danielson E, Fonseca FA, et al. N Engl J Med. 2008; 359:2195-207.

2. de Lorgeril M, Salen P, Abramson J, et al. Arch Intern Med. 2010; 170:1032-6.

3. Bassler D, Briel M, Montori VM, et al. JAMA. 2010; 303:1180-7.

4. The Emerging Risk Factors Collaboration. N Engl J Med. 2012; 367:1310-20.

5. Cholesterol Treatment Trialists’ Collaborators. Lancet. 2012; 380:581-90.

6. Heart Protection Study Collaborative Group. Lancet. 2011; 377:469-76.

7. McCormack JP, Allan GM. PLoS Med. 2010; 7:e1000196.

8. Koenig W, Sund M, Frohlich M, et al. Am J Epidemiol. 2003; 158:357-64.

9. Bogaty P, Brophy JM, Boyer L, et al. Arch Intern Med. 2005; 165:221-6.

10. Anderson TJ, Gregoire J, Hegele RA, et al. Can J Cardiol. 2013; 29:151-67.

Authors do not have any conflicts of interest to declare.