#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.
- 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
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