1. HDL-TG Axis in Metabolic Syndrome

2. Metabolic Syndrome : Synergistic Risk Factors
Atherogenic dyslipidaemia
High TG/Low HDL-C
High alcohol intake
Abdominal obesity
Lack of exercise
Hyperglycaemia Prediabetes
Accelerated
atherosclerosis
and CVD
High global
CV risk
Low fruit and vegetable consumption
Psychosocial stress
Smoking
Hypertension

3. Event - Free Survival (%) by HDL-C and TG
Low HDL-C / High TG increases MI risk irrespective of LDL-C

4. Is statin-mediated HDL-raising relevant to reduction in cardiometabolic risk and the slowing of atherosclerosis?

5. IVUS Trials: REVERSAL, CAMELOT, ACTIVATE, ASTEROID
Lowering LDL-C:HDL-C ratio to approx 1:1 stops atherosclerosis progression
Nicholls S, et al. JAMA. 2007;297:
PAV percent atheroma volume

6. Effect of Statins on Apo A1 production
Apo A1 production (% of control) * † 1 3 5 10 30
Drug conc (M) 50 ‡
Pitavastatin
Simvastatin
Atorvastatin
Hep G2 cells were treated for 48h with various concentrations of statins (1-30 μM and 50 μM).
The apo AI in the cultured medium was determined by ELISA kit.
*P<.05, †P<.001, ‡P<.01, Dunnett’s test.
Maejima. Biochem Biophys Res Commun 2004;324:835

7. Cholesterol Efflux and Reverse cholesterol transport
Liver
LDL-R CE CE
SR-B1
SR-B1
VLDL/LDL
CETP FC
Extrahepatic tissues
Arterial wall FC
ABCA1, ABCG1, SR-B1 CE
LCAT
HDL
apoAI FC
Bile
ApoAI

8. Atheroprotective functions of HDL
Anti-infectious activity
Reverse cholesterol transport/cellular cholesterol efflux
Anti-inflammatory activity
Anti-thrombotic activity
Vasodilatory activity/
endothelial repair
HDL
Anti-proteolytic activity
Immune system
Anti-apoptotic activity
Anti-oxidative activity

9. Slowing and Reversing Atherosclerosis
Inflammation
HDL
VLDL LDL
Libby (2001) Circulation 104:365