Prévention du risque cardiovasculaire : faut-il bloquer la CETP ?

Lipoproteins exchange of cholesterol esters and triglycerides through CETP (cholesteryl ester transfer protein), a transfer protein. It allows the exchange of cholesterol esters between HDL and LDL or VLDL triglycerides give back to HDL. In humans, this activity would allow more than 70 % of cholesterol esters present in the HDL to be transferred to LDL. The return of cholesterol to the liver via the LDL is very effective if they are properly metabolized. Otherwise, it is a particularly atherogenic metabolic pathway since the load LDL cholesterol esters which will accumulate in the circulation and be picked up by macrophages to promote lipid deposits. A number of preclinical and clinical data suggest that CETP would facilitate atherosclerosis in humans. By blocking its action, cholesterol esters remain on HDL to be eliminated by the liver. Genetic studies with loss of function mutations support this hypothesis, but the data are contradictory. In addition, it is unclear whether changes in the composition of lipoproteins obtained and especially HDL allow them to keep all their functions. Four molecules have been developed to block the activity of CETP with a consequent significant increase in HDL cholesterol of 30 to 130% depending on the degree of inhibition but also a reduction in LDL cholesterol up to 25%. Development of torcetrapib a potent inhibitor was discontinued due to adverse vascular effects primarily related to a specific action of this molecule on the renin-angiotensin system. Dalcetrapib which inhibited about 30% of the activity of the molecule has been interrupted for inefficiency. Two other potent inhibitors (anacetrapib and evacetrapib) are being developed and the first results of the cardiovascular intervention trials are expected in 2016.