olov wiklund wallenberg laboratory gothenburg sweden
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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