Chris PearceACS SSC

Aims and ObjectivesIntroduction – why look for new biomarkers?

Possible candidates.

hsCRP - Primary CHD. - Disadvantages.

Clinical relevance.

Traditional risk factorsLow specificity and sensitivity:

1.Coronary events occur in those with low risk lipid levels. (Ridker et al, 2002)

2.20-25% of events occur in those with only one risk factor. (Khot et al, 2003)

New biomarkers – Inflammation?

(Libby, 2004)

Candidates

(Ridker et al, 2004)

CandidateshsCRP =

High Sensitivity C-reactive Protein

(Ridker et al, 2004)

Emergence of hsCRP

(Ridker et al, 1997)

Emergence of hsCRP

(Ridker et al, 1997)

Incident myocardial infarction28, 263 women, used a

commercially available assay for hsCRP.

(Ridker et al, 2000)

27,939 women, showing CRP t0 be better than LDL.

(Ridker et al, 2002)

Clinical risk stratification tools

(Ridker and Cook, 2004)

(Cook et al, 2006)

Clinical risk stratification tools50% of

intermediate risk women re-classified.

More accurate correlation with observed disease.

(Ridker et al, 2007a)

Clinical risk stratification tools50% of

intermediate risk women re-classified.

More accurate correlation with observed disease.

(Ridker et al, 2007)

Response to statin therapy

Effects seen to be largely independent of changes in lipid concentration.

(Albert et al, 2001)

Response to statin therapy

Effects seen to be largely independent of changes in lipid concentration.

(Albert et al, 2001)

(Ridker et al, 2005)

Response to statin therapy

Future treatment

The JUPITER trial.

17,802 person with LDL cholesterol <3.36 mmol/Litre, but hsCRP over >2 mg/Litre from 26 countries.

Randomised to 20mg Rosuvastatin OD or placebo.

Enrolment completed by December 2006, with initial three year follow up.

(Ridker et al, 2007b)

Disadvantages to CRPGenetics – Is the ability to make CRP

genetically determined?

Inflammation – Can risk stratification be influenced by systemic inflammation?

Implications for practice America – 2003 CDCP/AHA publish first set of

guidance cautiously endorsing use of CRP as an adjunct to traditional risk factors.

(Pearson et al, 2003)

UK – 2007 NICE guidance on secondary prevention of MI gives no mention of CRP.

UK – 2010 NICE “Guidance on the prevention of cardiovascular disease at the population level,” expected.

http://www.nice.org.uk

ConclusionThe evidence base for CRP as a predictor of first

cardiovascular events is strong.

A response to statin therapy allows CRP to be clinically useful.

American regulatory bodies have endorsed the use of CRP.

In time, a host of inflammatory mediators may be used to calculate risk.

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