Olov Wiklund Wallenberg Laboratory

Gothenburg Sweden

Declaration of Interest

Research collaboration with Astra-Zeneca

Educational acitivies together with Pfizer, Astra-Zeneca and MSD

HDL - Triglycerides and CVD

Cholesterol in atherogenic lipoproteins

Non-HDL and CVD risk

Conclusion

Mendelian randomisation suggest the Lp(a) is causal for CVD

Kamstrup et al., JAMA 2009; 301:2331

Clarke et al., N Engl j Med 2009; 361:2518

Other suggested lipid biomarkers

Small dense LDL

HDL subclasses

Genetic markers

OxLDL antibodies

Lipid oxidation products

LpPLA2

A combination of N-BNP, CRP and TROPONIN T could improve risk estimation on

top of other risk factors

Hazard

ratio f

or

CV

D

CRP mg/ml

CHD risk after correction for conventional risk factors

CRP, mg/ml

Basal correction Corrected for conventional

Risk factors

CRP and non-vascular death

Is CRP a tool to better identify high risk patients ?

CRP does not improve discrimination of high risk patients!!

Conclusion from a meta-analysis

CRP does not perform better than the Framingham risk equation for discrimination.

The improvement in risk stratification or reclassification from addition of CRP to models based on established risk factors is small and inconsistent

Shah et al Int J Epidem 2009;38:217

Using plaque composition to identify Biomarkers

ApoAI in plasma is strongly correlated with

plaque stability

Serum apoAI (mg/ml)

2,01,81,61,41,21,0,8

Tis

su

e C

olla

ge

n (

% S

urf

ace

)

60

50

40

30

20

10

0

Serum apoAI (mg/ml)

2,01,81,61,41,21,0,8

Tis

su

e M

acro

ph

ag

es (

% S

urf

ace

)40

30

20

10

0

rs= -0.59, P < 0.01 rs= 0.64, P < 0.01

Solem et al., JIM, 2006

Vascular event and osteopontin in plaques

D.P.V. de Kleijn et al., ATVB 2010, 30:612

Biomarkers for future disease in CVD patients

Inflammation and long term mortality in ACS patients

Hartford et al JIM, 2007

CRP IL-6

PLA2 ICAM-1

Biomarkers for CVD in TNT

None of the non-lipid biomarkers added possibility to predict future CVD

CONCLUSION

In addition to conventional lipid biomarkers and other risk factors the contribution of new biomarkers is small.

Inflammation markers are the best documented of new potential biomarkers for CVD risk and atherosclerosis.

CRP could be considered especially in intermediate risk subjects.

Criteria for evaluation of novel biomarkers Proof of concept

Prospective evaluation

Incremental value

Clinical utility

Clinical outcomes

Cost effectiveness