Cholesterol Lowering Depends on Genes

The investigators found that genetic variants that mimic the effect of CETP inhibitors were associated with higher high-density lipoprotein cholesterol, lower LDL cholesterol, lower apoB and a corresponding lower risk of cardiovascular disease that was proportional to the reduction in LDL cholesterol. In fact, genetic variants that mimic the effect of CETP inhibitors had a very similar effect on reducing the risk of cardiovascular events as genetic variants that mimic the effect of statins, ezetimibe, and PCSK9 inhibitors when measured per unit reduction in LDL cholesterol. These results may help to explain the failure of some CETP inhibitors to reduce the risk of cardiovascular events despite robustly lowering LDL cholesterol," Ference said. "Adding a CETP inhibitor to a statin reduces LDL cholesterol out of proportion to apoB. Because the clinical benefit is determined by the reduction in apoB, rather than LDL cholesterol, combination therapy with a CETP inhibitor and a statin reduces the risk of cardiovascular events proportional to the attenuated reduction in apoB. This may be significantly less than expected for the observed change in LDL cholesterol depending on the degree of discordance between the reductions in apoB and LDL cholesterol." https://www.medpagetoday.com/MeetingCoverage/ESC/67586?xid=nl_mpt_DHE_2017-08-30&eun=g721819d0r&pos=1