Cholesteryl ester content in medium high‐density lipoprotein causally protective of atherosclerosis is identified, plus a target gene, PSRC1, with therapeutic potential for CAD, but not IS, supported by consistent evidence from multi‐omics layers of data, which also reveals that such therapeutic potential may be through downregulation of circulating proteins including TRP1, GRNs, and Pla2g12b, and upregulation of Neo1. Here, NEO1 is linked to atherosclerosis.