66 References Figure 1. Lipid Metabolism and Targets for Pharmacotherapy. In 1961, the investigators involved in the Framingham Heart Study identified serum cholesterol as one of the “factors of risk” for coronary heart disease. 1 Since then, numerous epidemiologic studies and randomized clinical trials have established that an elevated level of low-density lipoprotein (LDL) cholesterol is a major contributor to atherosclerotic cardiovascular disease. 2,3 As a consequence, the management of serum cholesterol levels has become a central objective in the effort to prevent cardiovascular events. The currently used therapies with demonstrated efficacy (see Table S1 in the Supplementary Appendix , available with the full text of this article at NEJM.org) predominantly target the apolipoprotein B–associated lipoproteins reflected in levels of LDL cholesterol, non–high-density lipoprotein cholesterol (non-HDL cholesterol), and triglycerides ( Figure 1 ). Figure 2. Five Key Point