[HDL and CETP in atherogenesis].
Despite optimal treatment of high low density lipoprotein (LDL) cholesterol with statins many cardiovascular events are not prevented. Additional therapeutic strategies are required to reduce the residual cardiovascular risk. Large epidemiological studies show an inverse correlation between the plasma concentration of high density lipoprotein (HDL) cholesterol and the incidence of cardiovascular events. Under physiological conditions, HDL is vasculoprotective and mediates the reverse cholesterol transport. However, new studies suggest that HDL particles represent a heterogeneous population. Under several pathophysiological conditions, HDL was shown to promote atherogenesis and inflammation. Interventional studies and metaanalyses examining the effect of increasing HDL cholesterol have reported mixed results. Inhibition of cholesteryl ester transfer protein (CETP) is a new and potent strategy to increase HDL concentrations. However, the first CETP-inhibitor torcetrapib increased blood-pressure and increased cardiovascular events despite increasing HDL. The blood-pressure increasing effects are not known for more recently developed CETP inhibitors such as dalcetrapib and anacetrapib nor in patients with genetic CETP deficiency. An increase of HDL cholesterol does not necessarily imply an improvement of the functional properties of HDL such as reverse cholesterol transport. An important open question remains the functional characterization of HDL generated by CETP inhibition. Important current clinical endpoint studies with new CETP inhibitors will elucidate whether increasing HDL by CETP inhibition leads to a reduction of cardiovascular events.
Pöss
J
J
Klinik für Innere Medizin III, Universität des Saarlandes, Homburg. janine.poess@gmx.de
Böhm
M
M
Laufs
U
U
D000577:Amides; D000924:Anticholesteremic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D050197:Atherosclerosis / Q000097:blood* / Q000517:prevention & control; D053480:Cholesterol Ester Transfer Proteins / Q000037:antagonists & inhibitors* / Q000502:physiology*; D008076:Cholesterol, HDL / Q000097:blood*; D008078:Cholesterol, LDL / Q000097:blood; D002995:Clofibric Acid / Q000009:adverse effects / Q000627:therapeutic use; D003324:Coronary Artery Disease / Q000097:blood / Q000517:prevention & control; D004952:Esters; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D008019:Life Style; D009539:Nicotinic Acids / Q000009:adverse effects / Q000627:therapeutic use; D023303:Oxazolidinones / Q000009:adverse effects / Q000627:therapeutic use; D011804:Quinolines / Q000009:adverse effects / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D013438:Sulfhydryl Compounds / Q000009:adverse effects / Q000627:therapeutic use; D016896:Treatment Outcome
D000577:Amides; D000924:Anticholesteremic Agents; D053480:Cholesterol Ester Transfer Proteins; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D004952:Esters; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D009539:Nicotinic Acids; D023303:Oxazolidinones; D011804:Quinolines; D013438:Sulfhydryl Compounds; C411602:dalcetrapib; C483909:torcetrapib; D002995:Clofibric Acid; C530884:anacetrapib