Those with primary elevations of LDL-C 160 mg/dL (4.1 mmol/L) have elevated lifetime ASCVD risk and benefit from statin therapy.S4.4.2-21,S4.4.2-22,S4.4.2-25, Increased ASCVD riskS4.4.2-2 is seen with metabolic syndrome;S4.4.2-20 inflammatory diseases, including psoriasisS4.4.2-31 and RA; and HIV when treated with protease inhibitors.S4.4.2-32 In women, a history of pregnancy complicated by preeclampsia or premature menopause (age <40 years) also enhances ASCVD risk (see Section 4.4.5.3.). If measured, ABI <0.9 has been shown to reclassify risk by the 2013 Risk Assessment The presence of risk-enhancing factors may affect the threshold for statin initia- tion or intensification (see Sections 4.4.2, 4.4.4, and 4.5). Finally, in selected individuals, biomark- ers, if measured, may identify individuals with increased risk of ASCVD events. Lp(a) levels, especially in those with a family history of prema- ture ASCVD, can increase risk.S4.4.2-16 However, no available RCT evidence supports Lp(a) levels as a target of therapy. Moderate primary elevations of triglycerides, non HDL-C (TC minus HDL-C), and, if measured, apolipoprotein B (apoB) can improve selection of those at increased ASCVD risk.S4.4.2-22 6. Evidence shows that a CAC score of zero can down-risk individuals who otherwise would qualify for a statin on the basis of their ASCVD 10-year risk. The ability to select those who would benefit greatly from statin therapy, as shown by RCTs in primary-prevention populationsS4.4.2-6,S4.4.2-8 and yet to withhold statin therapy in those least likely to benefit would improve specificity.S4.4.2-34 For example, a CAC score of zero in an analysis of pooled US population-based studies accurately discriminated between lower and higher CHD risk in older adults.S4.4.2-19,S4.4.2-27 The BioImage Study in older adultsS4.4.2-15 showed improved detection of individuals not likely to benefit from statins when the CAC score was zero. 