"Badly worded, what I meant was the effect on MACE was more pronounced in severe cases.  The company has made that clear in all its presentations dealing with the results of phase two trials"

So basically you are asking why does apabetalone, which has been shown to increase HDL, improve glucose metabolism, and reduce components/mediators of vascular inflammation, vascular calcification, complement and coagulation cascades, elicit greater effects in individuals at high risk that have low-HDL, impaired glucose metabolism, and increased expression/activity of vascular inflammation, vascular calcification and complement and coagulation cascades?

Kind of seems like you answered your own question. But from a molecular perspective, these processes above are hyperactive in the sicker patients and the increased transcription of genes involved in these processes seems to be dependent upon BET protein function. So apabetalone seems to "cool off" these hyper-active transcriptional changes back to baseline or near baseline. Overactive BET protein-driven transcription contributes to the disease state. Bromodomain-2 selective BET inhibition by apabetalone restrains BET-protein mediated transcription to normalize the expression level of these genes back to a more healthy state.

BearDownAZ