Figure 3.

Effect of exposure to lower low-density lipoprotein cholesterol (LDL-C) by mechanism of LDL-C lowering. Panel A shows the effect of genetic variants or genetic scores combining multiple variants in the genes that encode for the targets of currently available LDL-C-lowering therapies, adjusted for a standard decrement of 0.35 mmol/L lower LDL-C, in comparison with the effect of lower LDL-C mediated by variants in the LDL receptor gene. Panel B shows the effect of currently available therapies that act to primarily lower LDL-C through the LDL receptor pathway, adjusted per millimole per litre lower LDL-C. Both the naturally randomized genetic data in Panel A and the data from randomized trials in Panel B suggest that the effect of LDL-C on the risk of cardiovascular events is approximately the same per unit change in LDL-C for any mechanism that lowers LDL-C via up-regulation of the LDL receptor where the change in LDL-C (which is used in clinical medicine to estimate the change in LDL particle concentration) is likely to be concordant with changes in LDL particle concentration.