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

CLINICAL QUESTION

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

BOTTOM LINE

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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EVIDENCE

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 screened, 17,802 included) with 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.

No RCT 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 calculator) did 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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