The combination of LDL-C and VLDL-C is called non HDL-C and is more atherogenic than either lipoprotein alone. The main protein embedded in LDL and VLDL is apolipoprotein B (apoB), and like non HDL- C, apoB is a stronger indicator of atherogenicity than LDL-C alone. 2.1.2. Cholesterol, LDL-C, and ASCVD Evidence that serum cholesterol contributes to ASCVD comes from several sources: animal studies, genetic forms of hypercholesterolemia, epidemiological stud- ies, and RCTs. US population studiesS2.1.2-1,S2.1.2-2 suggest that optimal total cholesterol levels are about 150 mg/ dL (3.8 mmol/L), which corresponds to an LDL-C level of about 100 mg/dL (2.6 mmol/L). Adult populations with cholesterol concentrations in this range manifest low rates of ASCVD.S2.1.2-3 RCTs of cholesterol-lowering drugs in high-risk patients confirm that LDL-C lowering produces marked reductions in ASCVD. This confirms the general principle that lower is better for LDL- The present guideline looks to evidence from new RCTs to aid in the translation of RCT data to the individual patient to provide net benefit.S2.1.2-7 2.1.3. LDL-C and Other Risk Factors Although LDL-C is a primary cause of atherosclero- sis, other risk factors contribute, as well. The major risk factors include cigarette smoking, hypertension, dysglycemia, and other lipoprotein abnormalities. Be- cause atherosclerosis progresses with advancing age, a person s age also counts as a risk factor. By combin- ing all major risk factors into a prediction equation, an individual s probability of developing ASCVD can be estimated. The Framingham Heart StudyS2.1.3-1 took the lead in creating risk-prediction equations. These were improved in the 2013 ACC/AHA cholesterol guideli- by compiling data from 5 community-based cohorts that were broadly representative of the US population. 