HDL-TG Axis in Metabolic Syndrome

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Presentation transcript:

HDL-TG Axis in Metabolic Syndrome

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

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

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

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;297:499-508. PAV percent atheroma volume

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

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

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

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