Epidemiological evidence suggested low HDL cholesterol was a stronger predictor of cardiac events than high LDL cholesterol, but Mendelian randomization and CTP inhibitors have shown HDL is not causal.

“before we get there hdl cholesterol was the rage okay the total rage because the epidemiological evidence couldn't be clearer in fact it was four times more clear my recollection was that framingham demonstrated low hdlc was four times more predictive of cardiac events than high ldlc am i am i remembering that correctly oh yeah i'm not sure it's that multiple yeah but it's it's multiples and and it turns out as we know now at least from the ctp inhibitors that you can't manipulate hdl and change outcomes and that's one of the elements of demonstrating an overall causal relationship”