Certain CETP variants and drugs show smaller risk reduction than predicted when lowering cholesterol mass discordantly with ApoB.

“The lowering of LDL with those variants in those drugs, it lowers the cholesterol mass, but there's a discordant lowering of APOB or LDL particle number. So every single LDL particle has an APOB protein on it. And when we get into the mechanisms, this is going to be very central to the lipid hypothesis. And so if you lower cholesterol mass, but your APOB doesn't drop that much, you basically have just made each particle smaller. And what we see is in that particular subset of varants there is a small risk reduction but it's basically explained by the small decrease in apo and you don't get the predicted risk reduction that you would get with reducing LDL cholesterol”