 | | Changing world of CV prevention: Does HDL-increase still fit the picture? |
|  | | Increased survival compared to ‘70s |
|
 | | Statin therapy in CV prevention % of events not avoided |
|  | | Is HDL-c(-raising) a good candidate? |
|
 | | HDL as therapeutic target |
|  | | Atheroma formation & Plaque rupture |
|
 | | I. Initiation: (mm)LDL accumulation & phagocytosis |
|  | | HDL mediates ‘reverse cholesterol transport’ |
|
 | | HDL increases cholesterol excretion whole-body as well as ‘vascular’ |
|  | | Plasma HDL ‘not related’ to efficacy of Reverse cholesterol transport ? |
|
 | | RCT in low HDL patients |
|  | | Below ‚threshold‘ HDL rate-limiting for RCT ? |
|
 | | II. Progression/destabilization Cellular infiltration & matrix degradation |
|  | | HDL attenuates inflammation |
|
 | | rHDL limits inflammatory respons Endotoxin challenge |
|  | | II. Progression & destabilization endothelial dysfunction |
|
 | | Endothelial Function: Restored endothelial function upon HDL infusion in ABC-A1 heterozygous subjects |
|  | | III. Atherothrombosis cascade activation by tissue factor exposure |
|
 | | HDL attenuates thrombosis |
|  | | HDL and the risk of venous thrombosis |
|
 | | HDL as ‘carrier’ of protective molecules |
|  | | HDL as therapeutic target |
|
 | | HDL and CHD in Framingham HS A potent risk factor |
|  | | HDLs’ apoAI The Interheart study |
|
 | | Heart Protection study low HDL predicts events during statin therapy |
|  | | HDL as therapeutic target |
|
 | | HDL metabolism The Key Players |
|  | | Heterozygosity for apoA-IL178P Intima Media Thickness |
|
 | | Genetic Disorders of Human HDL Metabolism and Risk of Atherosclerosis: Intima Media Thickness |
|  | | CETP SNPs and HDL changes Meta-analysis |
|
 | | Lower CETP-status with higher HDLc protects against atherosclerosis …. |
|  | | ABC-AI SNPs and HDL changes Copenhagen City Heart study |
|
 | | Lower HDL due to ABC-AI mutation not associated with increased CV risk ? |
|  | | Is life-time exposure to low HDL a risk factor for cardiovascular disease ? HDL ‘genes’ in Genome wide association studies ? |
|
 | | LDL genes in GWAS Fusion, Sardinia, DGI |
|  | | HDL genes in GWAS Fusion, Sardinia, DGI |
|
 | | Common variants contribute to polygenic dyslipidemia |
|  | | Common SNPs associate with dyslipidemia Malmo Diet and Cancer Study |
|
 | | Genotype associates with CV-disease |
|  | | Summary Genetics: |
|
 | | HDL as therapeutic target |
|  | | Benefits of raising HDL human studies |
|
 | | Nicotinic Acid Non-specific effects |
|  | | rHDL infusion in ACS ERASE study |
|
 | | HDL delipidation and atheroma regression Comparison apoAI milano infusion |
|  | | The CETP story How to continue? |
|
 | | Torcetrapib and CV-events Illuminate study |
|  | | Hazard ratio for CHD death/MI according to HDL level adjusted or baseline HDL level |
|
 | | Torcetrapib associates with blood pressure increase |
|  | | Radiance 1 & 2 Blood pressure change vs. IMT progression |
|
 | | What causes CV-harm: CETP-inhibition or compound-specific toxicity? |
|  | | Stroes, Br J Pharmacol 2009 (revision) |
|
 | | Constant BP following dalcetrapib Analysis in 12-week study |
|  | | Constant BP following Anacetrapib |
|
 | | Summary |
|  | | HDL as therapeutic target |
|
 | | How to proceed with HDL |
|  | | New Challenge: you can’t target what you can’t measure |
|
 | | 13C-cholesterol infusion: Efflux Measured from Rise-to-Plateau Kinetics |
|  | | Impact on lipid metabolism of LXR agonists |
|
 | | LXR Agonist and RCT experiments in mice |
|  | | LXR agonist reduces atherosclerosis |
|
 | | Trans-Intestinal Cholesterol Excretion a novel HDL-independent excretion target? |
|  | | 13C-cholesterol infusion in patients ABC-AI/apoAI/LCAT carriers +/- rHDL infusion |
|
 | | Other targets |
|  | | Summary |
|
 | | The end of the ‘HDL’ era ? |
|
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